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    Associations of urinary epidermal growth factor and monocyte chemotactic protein-1 with kidney involvement in patients with diabetic kidney disease. Wu Liang,Li Xiao-Qian,Chang Dong-Yuan,Zhang Huifen,Li Jun-Juan,Wu Shou-Ling,Zhang Lu-Xia,Chen Min,Zhao Ming-Hui Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association BACKGROUND:In diabetic kidney disease (DKD), it is important to find biomarkers for predicting initiation and progression of the disease. Besides glomerular damage, kidney tubular injury and inflammation are also involved in the development of DKD. The current study investigated the associations of urinary epidermal growth factor (uEGF), monocyte chemotactic protein-1 (MCP-1) and the uEGF:MCP-1 ratio with kidney involvement in patients at early and advanced stages of DKD. METHODS:The concentration of uEGF and uMCP-1 was measured in two Chinese population-based studies. The associations of uEGF, uMCP-1 and uEGF/MCP-1 with occurrence of DKD were studied in a cross-sectional study (n = 1811) of early stage DKD. Associations of baseline uEGF, uMCP-1 and uEGF/MCP-1 with kidney outcome were assessed in a longitudinal cohort (n = 208) of advanced-stage DKD. RESULTS:In both studies, positive correlations were found between uEGF/urine creatinine (Cr) and estimated glomerular filtration rate (eGFR) at sampling and between uMCP-1/Cr and urinary albumin:creatinine ratio (uACR). In the cross-sectional study, uEGF/Cr and uEGF/MCP-1 were negatively associated with the occurrence of DKD {odds ratio (OR) 0.65 [95% confidence interval (CI) 0.54-0.79], P < 0.001; 0.82 (0.71-0.94), P = 0.005, respectively}. In the longitudinal cohort, the uEGF:MCP-1 ratio correlated more closely with the percentage change of eGFR slope (r = 0.33, P < 0.001) as compared with uEGF/Cr or uMCP-1/Cr alone. The composite endpoint was defined as end-stage renal disease or 30% reduction of eGFR. These three markers were independently associated with composite endpoint after adjusting for potential confounders [hazard ratio 0.76 (0.59-1.00), P = 0.047 for uEGF/Cr; 1.18 (1.02-1.38), P = 0.028 for uMCP-1/Cr; 0.79 (0.68-0.91), P = 0.001 for uEGF/MCP-1]. CONCLUSION:In Chinese patients, urinary EGF/MCP-1 was negatively associated with the occurrence of DKD. Moreover, uEGF/MCP-1 had a better ability to predict the composite endpoint and correlated more closely with kidney function decline in advanced DKD as compared with uEGF/Cr or uMCP-1/Cr alone. 10.1093/ndt/gfy314
    Monocyte to high density lipoprotein ratio in patients with acute kidney injury after cardiac surgery. Huang Wenjuan,Wang Lei,Wan Xin Perfusion BACKGROUND:The Monocyte to high density lipoprotein ratio (MHR) has been postulated as a novel parameter associated with adverse renal and cardiovascular outcomes. In this study we investigated the association of MHR with cardiac surgery-associated acute kidney injury (CSA-AKI). METHODS:In this retrospective study, we analyzed the data pertaining to 1505 patients undergoing cardiopulmonary bypass (CPB) surgery. The CSA-AKI, which was defined using Kidney Disease Improving Global Outcomes criteria. Concurrently, a retrospective scan of patient files was conducted and information relevant to nephropathy such as the level of their serum creatinine (SCr), Blood urea nitrogen (BUN), uric acid (UA), serum cystatin C (Cys-C), total cholesterol (TC), triglycerides (TG), glucose and MHR, ejection fraction, CPB duration time, and other indicators. RESULTS:About 1505 patients were studied of whom 195 developed AKI. MHR was significantly higher in the AKI patients (p = 0.001). In multivariate logistic regression analysis, MHR, UA, Cys-C, age, glucose, and history of chronic kidney disease or hypertension were independently correlated with CSA-AKI. CONCLUSIONS:As a laboratory index, the elevated MHR is convenient, independent, and a useful predictor for CSA-AKI. 10.1177/02676591211041945
    The effect of hemodialysis, peritoneal dialysis and renal transplantation on nutritional status and serum micronutrient levels in patients with end-stage renal disease; Multicenter, 6-month period, longitudinal study. Dizdar Oguzhan Sıtkı,Yıldız Abdulmecit,Gul Cuma Bulent,Gunal Ali Ihsan,Ersoy Alparslan,Gundogan Kursat Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) PURPOSE:Nutritional status and micronutrient levels of end stage renal disease (ESRD) patients may vary depending on the mode of renal replacement therapy (RRT). We aimed to compare the effects of hemodialysis, peritoneal dialysis (PD) and renal transplantation (RT) on micronutrient levels and nutritional status in ESRD patients. PATIENTS AND METHODS:A total of 77 ESRD patients who had not received RRT were included in this prospective longitudinal study. All ESRD patients underwent a blood serum analysis that assessed the micronutrients such as selenium, copper, zinc, chromium, retinol, thiamine and vitamin B6 as well as a nutritional status assessment. After the baseline assessments and the initiation of RRT was accomplished, all patients were followed for 6 months. RESULTS:The study showed significant improvements in subjective global assessment scores (percentage increases in score A were 26.6 and 36.6; p = 0.039 and p = 0.001; respectively), mid-arm circumference and the skin-fold thicknesses (p < 0.001, p < 0.001; respectively) in the RT and hemodialysis groups. The examinations at sixth month revealed a significant increase in body weight (4.8 kg; p = 0.002) and albumin levels (0.6 g/dL; p < 0.001) in only RT group. Zinc, thiamin and vitamin B6 were the most deficient micronutrients (44.1 %, 24.7 % and 35.1 %; respectively) in ESRD patients. There was a significant increase in selenium and retinol levels (p = 0.020 and p < 0.001; respectively) but a significant decrease in thiamin levels (p = 0.041) in RT patients. A significant increase in retinol levels (p = 0.028) and a significant decrease in thiamin levels (p = 0.022) was observed in the hemodialysis patients. However, no significant change in micronutrient levels was observed in the PD patients. CONCLUSION:The results support the recommendation that ESRD patients should be supplemented with water-soluble vitamins, especially thiamine and vitamin B6, and trace elements, especially zinc. RT appears to be superior to other modes of RRT when examining SGA score, anthropometric measurements, albumin and micronutrient levels. 10.1016/j.jtemb.2020.126498
    Relationships of the Trace Elements Zinc and Magnesium With Diabetic Nephropathy-Associated Renal Functional Damage in Patients With Type 2 Diabetes Mellitus. Feng Jianan,Wang Heyuan,Jing Zhe,Wang Yue,Wang Wanning,Jiang Yanfang,Sun Weixia Frontiers in medicine Zinc (Zn) and magnesium (Mg) are essential trace elements in humans. Their deficiency may be associated with inflammation and oxidative stress (OS) in patients with diabetic nephropathy (DN), but the mechanisms involved have not been fully characterized. We aimed to investigate the relationships between circulating concentrations of Zn and Mg and pro-inflammatory factors with DN-associated renal functional damage in patients with type 2 diabetes mellitus (T2DM). To this end, we studied 20 healthy people, 24 patients with T2DM, and 59 patients with T2DM and T2DN. Serum and urine Zn and Mg concentrations were measured using the 2-(5-nitro-2-pyridylazo)-5-(N-propyl-N-sulfopropylamine) phenol (nitro-PAPS) chromogenic method and the xylidyl blue method, respectively, and the circulating concentrations of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-α (TNF-α)] were measured using flow cytometry. The serum concentrations of Zn and Mg were significantly lower in patients with T2DM and DN than in healthy controls. Serum Zn, urine Zn, and urine Mg concentrations decreased, while those of IL-6 and IL-8 increased with the progression of DN-associated renal functional damage. Furthermore, the serum and urine Zn concentrations negatively correlated with the serum IL-6 and IL-8 concentrations. Notably, the serum Zn concentration was found to independently protect against DN in patients with T2DM. Hypozincemia may be associated with the T2DN-associated renal functional damage because it exacerbates inflammation. 10.3389/fmed.2021.626909
    Trace elements in type 2 diabetes mellitus and their association with glycemic control. Hasanato Rana Mw African health sciences Background:Alterations in serum levels of trace elements reported in type 2 diabetes mellitus (T2DM) have been linked with induction of T2DM and associated complications. Objectives:To assess serum levels of copper (Cu), zinc (Zn) and selenium (Se) in T2DM patients with adequate and poor glycemic control. Patients and methods:This study was performed at King Khalid University Hospital, Riyadh. A total of 100 consenting T2DM patients comprising of 50 patients with glycated hemoglobin (HbA1c) less than 6.5% and 50 patients with HbA1c more than 6.5% along with a group of 50 normal healthy individuals were included in the study. Serum levels of Cu, Zn and Se were measured by inductively coupled plasma-mass spectrometry (ICP-MS) instrument. Results:Among T2DM patients with HbA1c <6.5%, mean serum Cu levels (13.4+4.3µmol/L) were not different from the controls (14.5+1.92µmol/L) whereas Zn (9.9+2.7µmol/Lvs15+3.2µmol/L;p<0.0001) and Se levels (1+0.2µmol/Lvs1.62+0.2µmol/L; p<0.0004) were lower than the controls. Among T2DM patients with HbA1c >6.5% mean serum Cu (18.1+4.1µmol/Lvs14.5+1.9µmol/L; p<0.0001), Zn (15+3.2µmol/Lvs13.5+1.9µmol/L; p<0.009) and Se (1.62+0.2µmol/Lvs1.17+0.16µmol/L;p<0.0001) were significantly higher than the controls. HbA1c% negatively correlated with HbA1c >6.5% (r = -0.302; p<0.03). Conclusion:Cu, Zn and Se homeostasis was altered in T2DM patients and varied with glycemic control. 10.4314/ahs.v20i1.34
    The Relationship Between Heavy Metal Exposure, Trace Element Level, and Monocyte to HDL Cholesterol Ratio with Gestational Diabetes Mellitus. Onat Taylan,Demir Caltekin Melike,Turksoy Vugar Ali,Baser Emre,Aydogan Kirmizi Demet,Kara Mustafa,Yalvac Ethem Serdar Biological trace element research The objective of this study is to assess the levels of heavy metals (cadmium, lead, antimony, mercury, and arsenic), which are also called endocrine-disrupting chemicals, and trace elements (chromium-III, chromium-VI, zinc, copper, and selenium) vs. monocyte to HDL ratio among pregnant women with gestational diabetes mellitus (GDM). A total of 112 pregnant women (60 with GDM and 52 healthy women) were included in this case-control study. Analysis of heavy metals and trace elements were performed in inductively coupled plasma mass spectrometer. Heavy metals (cadmium, lead, antimony, mercury, and arsenic), trace elements (chromium-III, chromium-VI, zinc, copper, and selenium), and metabolic parameters were assessed in both groups. It was determined that the levels of cadmium, lead, antimony, and copper were higher (p < 0.05) and levels of chromium-III, zinc, and selenium were lower (p < 0.05) among the GDM group compared to the control group, whereas there was a statistically insignificant difference between the two groups, regarding the levels of copper, mercury, and arsenic (p > 0.05). Moreover, the monocyte to HDL ratio was higher in the GDM group (p < 0.05), and the insulin resistance was significantly higher as well (p < 0.05). The results of our study demonstrated that environmental factors could be effective in the etiology of GDM. Toxic heavy metals, through inducing Cu, OS, and chronic inflammation, and other trace elements, either directly by impacting insulin secretion or through weakening the body's antioxidant defense system, could play a role in the occurrence of GDM. 10.1007/s12011-020-02499-9
    Contribution of trace element exposure to gestational diabetes mellitus through disturbing the gut microbiome. Zhang Yuqing,Chen Ting,Zhang Yiyun,Hu Qi,Wang Xu,Chang Hang,Mao Jian-Hua,Snijders Antoine M,Xia Yankai Environment international BACKGROUND:A healthy gut microbiome is critical for glucose metabolism during pregnancy. In vivo studies indicate that trace element affects the composition and function of the gut microbiome and potentially leads to metabolic disorders but their relationships are largely unknown. We aimed to investigate whether the gut microbiome plays a role in the relationship between trace element exposure and gestational diabetes mellitus (GDM). METHODS:In a prospective cohort study, serum levels of 22 trace elements and the fecal gut microbiome composition were assessed in 837 pregnant women in the second trimester between 22 and 24 weeks of pregnancy prior to GDM diagnosis. Regression and mediation analysis were used to explore the link between element exposure, the gut microbiome, and GDM. RESULTS:128 pregnant women (15.3%) were diagnosed with GDM. No individual trace elements were found significantly associated with GDM. In contrast, the composition of the gut microbiome was dramatically altered in women later diagnosed with GDM and characterized by lower alpha diversity and lower abundance of co-abundance groups (CAGs) composed of genera belonging to Ruminococcaceae, Coriobacteriales, and Lachnospiraceae. Rubidium (Rb) was positively associated with alpha diversity indices while mercury (Hg) and vanadium (V) showed negative associations. Elements including rubidium (Rb), thallium (Tl), arsenic (As), and antimony (Sb) were significantly correlated with GDM-related CAGs and mediation analysis revealed that Rb and Sb were inversely related to GDM risk by altering abundance levels of CAGs enriched for Lachnospiraceae, Coriobacteriales, and Ruminococcaceae. CONCLUSION:Our study indicates that trace element exposure is associated with specific gut microbiome features that may contribute to GDM development, which could provide a new avenue for intervening in environmental exposure-related GDM. 10.1016/j.envint.2021.106520
    Multiplexed measurement of candidate blood protein biomarkers of heart failure. Tonry Claire,McDonald Ken,Ledwidge Mark,Hernandez Belinda,Glezeva Nadezhda,Rooney Cathy,Morrissey Brian,Pennington Stephen R,Baugh John A,Watson Chris J ESC heart failure AIMS:There is a critical need for better biomarkers so that heart failure can be diagnosed at an earlier stage and with greater accuracy. The purpose of this study was to design a robust mass spectrometry (MS)-based assay for the simultaneous measurement of a panel of 35 candidate protein biomarkers of heart failure, in blood. The overall aim was to evaluate the potential clinical utility of this biomarker panel for prediction of heart failure in a cohort of 500 patients. METHODS AND RESULTS:Multiple reaction monitoring (MRM) MS assays were designed with Skyline and Spectrum Mill PeptideSelector software and developed using nanoflow reverse phase C18 chromatographic Chip Cube-based separation, coupled to a 6460 triple quadrupole mass spectrometer. Optimized MRM assays were applied, in a sample-blinded manner, to serum samples from a cohort of 500 patients with heart failure and non-heart failure (non-HF) controls who had cardiovascular risk factors. Both heart failure with reduced ejection fraction (HFrEF) patients and heart failure with preserved ejection fraction (HFpEF) patients were included in the study. Peptides for the Apolipoprotein AI (APOA1) protein were the most significantly differentially expressed between non-HF and heart failure patients (P = 0.013 and P = 0.046). Four proteins were significantly differentially expressed between non-HF and the specific subtypes of HF (HFrEF and HFpEF); Leucine-rich-alpha-2-glycoprotein (LRG1, P < 0.001), zinc-alpha-2-glycoprotein (P = 0.005), serum paraoxanse/arylesterase (P = 0.013), and APOA1 (P = 0.038). A statistical model found that combined measurements of the candidate biomarkers in addition to BNP were capable of correctly predicting heart failure with 83.17% accuracy and an area under the curve (AUC) of 0.90. This was a notable improvement on predictive capacity of BNP measurements alone, which achieved 77.1% accuracy and an AUC of 0.86 (P = 0.005). The protein peptides for LRG1, which contributed most significantly to model performance, were significantly associated with future new onset HF in the non-HF cohort [Peptide 1: odds ratio (OR) 2.345 95% confidence interval (CI) (1.456-3.775) P = 0.000; peptide 2: OR 2.264 95% CI (1.422-3.605), P = 0.001]. CONCLUSIONS:This study has highlighted a number of promising candidate biomarkers for (i) diagnosis of heart failure and subtypes of heart failure and (ii) prediction of future new onset heart failure in patients with cardiovascular risk factors. Furthermore, this study demonstrates that multiplexed measurement of a combined biomarker signature that includes BNP is a more accurate predictor of heart failure than BNP alone. 10.1002/ehf2.13320
    Prediction of the effect of dapagliflozin on kidney and heart failure outcomes based on short-term changes in multiple risk markers. Idzerda Nienke M A,Stefansson Bergur V,Pena Michelle J,Sjostrom David C,Wheeler David C,Heerspink Hiddo J L Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association BACKGROUND:Besides improving glucose control, sodium-glucose co-transporter 2 inhibition with dapagliflozin reduces blood pressure, body weight and urinary albumin:creatinine ratio (UACR) in patients with type 2 diabetes (T2DM). The parameter response efficacy (PRE) score was developed to predict how short-term drug effects on cardiovascular risk markers translate into long-term changes in clinical outcomes. We applied the PRE score to clinical trials of dapagliflozin to model the effect of the drug on kidney and heart failure (HF) outcomes in patients with T2DM and impaired kidney function. METHODS:The relationships between multiple risk markers and long-term outcome were determined in a background population of patients with T2DM with a multivariable Cox model. These relationships were then applied to short-term changes in risk markers observed in a pooled database of dapagliflozin trials (n = 7) that recruited patients with albuminuria to predict the drug-induced changes to kidney and HF outcomes. RESULTS:A total of 132 and 350 patients had UACR >200 mg/g and >30 mg/g at baseline, respectively, and were selected for analysis. The PRE score predicted a risk change for kidney events of -40.8% [95% confidence interval (CI) -51.7 to -29.4) and -40.4% (95% CI -48.4 to -31.1) with dapagliflozin 10 mg compared with placebo for the UACR >200 mg/g and >30 mg/g subgroups. The predicted change in risk for HF events was -27.3% (95% CI -47.7 to -5.1) and -21.2% (95% CI -35.0 to -7.8), respectively. Simulation analyses showed that even with a smaller albuminuria-lowering effect of dapagliflozin (10% instead of the observed 35% in both groups), the estimated kidney risk reduction was still 26.5 and 26.8%, respectively. CONCLUSIONS:The PRE score predicted clinically meaningful reductions in kidney and HF events associated with dapagliflozin therapy in patients with diabetic kidney disease. These results support a large long-term outcome trial in this population to confirm the benefits of the drug on these endpoints. 10.1093/ndt/gfz064
    Comparison of objective nutritional indexes for the prediction of in-hospital mortality among elderly patients with acute heart failure. Alataş Ömer Doğan,Biteker Murat,Yildirim Birdal,Acar Ethem,Gökçek Kemal European journal of emergency medicine : official journal of the European Society for Emergency Medicine OBJECTIVES:The association between objective nutritional indexes and prognosis in patients with acute heart failure have not been well studied. Therefore, we aimed to compare the prognostic value of modified Glasgow prognostic score, prognostic nutritional index, controlling nutritional status score, and geriatric nutritional risk index for the prediction of in-hospital mortality in patients with acute heart failure. METHODS:All consecutive elderly patients (aged ≥65 years) who had tests for C-reactive protein, total lymphocyte count, total cholesterol, and albumin levels at admission, and hospitalized due to acute heart failure were retrospectively included. The primary endpoint of the study was in-hospital mortality. We used a base model for the prediction of in-hospital mortality, including age, gender, log N-terminal pro-B-type natriuretic peptide, and the presence of coronary artery disease. We added each of the malnutrition scores, in turn, to the base model and used C-statistics to evaluate model discrimination in survival analysis. RESULTS:A total of 628 patients were included, and 80 (12.7%) of the patients died during the hospital stay. Multivariate analysis showed that older age, prognostic nutritional index < 41.2, controlling nutritional status score > 5, geriatric nutritional risk index <92, and modified Glasgow prognostic score were independent predictors of in-hospital mortality. Among the malnutrition scores, geriatric nutritional risk index increased model performance most compared with base model. CONCLUSION:Though all objective nutritional indexes were associated with prognosis in elderly patients with acute heart failure, geriatric nutritional risk index was superior to other scores in predicting in-hospital mortality. 10.1097/MEJ.0000000000000690
    Mechanisms and prediction of short-term natriuretic effect of sodium-glucose cotransporter 2 inhibitor in heart failure patients coexisting type 2 diabetes mellitus. Fukuoka Shusuke,Dohi Kaoru,Takeuchi Tetsushiro,Moriwaki Keishi,Ishiyama Masaki,Omori Taku,Fujimoto Naoki,Ito Masaaki Heart and vessels The mechanisms of the diuretic effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor and its predictors in heart failure (HF) patients with coexisting type 2 diabetes mellitus (T2DM) remain under investigation. A total of 40 hospitalized HF patients with T2DM (68 ± 13 years old, male gender 63%) were prospectively enrolled and received ipragliflozin at a dose of 50 mg once daily after breakfast for at least 4 consecutive days. They underwent first-morning blood and urine tests, and 24-h urine tests before and after short-term ipragliflozin therapy. Daily urine volume significantly increased from 1365 ± 511 mL/day on day 0 to 1698 ± 595 mL/day on day 3 (P < 0.001), which resulted in significant decreases in body weight and plasma brain natriuretic peptide level. Changes in 24-h urine volume were strongly and independently correlated with changes in 24-h urine sodium excretion (r = 0.80, P < 0.001), but was not significantly correlated with those in 24-h urine sugar excretion (r = 0.29, P = 0.07). Lower concentration of first-morning urine sodium and higher loop diuretic dosage before ipragliflozin therapy were associated with urine volume increment with ipragliflozin therapy, and former retained its independent predictor (Odds ratio 0.96, 95% CI 0.93-0.99, P = 0.02). First-morning urine sodium ≤ 53 mEq/L and baseline loop diuretics ≥ 20 mg/day predicted increased urine volume on day 3 with high diagnostic accuracy. Ipragliflozin has acute natriuretic activity, and first-morning urine sodium and baseline dosage of loop diuretics strongly predicted the diuretic effects. Ipragliflozin therapy may restore responsiveness to loop diuretics in symptomatic HF patients with T2DM. 10.1007/s00380-020-01597-x
    Factors associated with heart failure hospitalization in patients with high sodium excretion: subanalysis of the ESPRIT, evaluation of sodium intake for the prediction of cardiovascular events in Japanese high-risk patients, cohort study. Sadanaga Tsuneaki,Hirota Shinichi,Mitamura Hideo Heart and vessels We have reported that high sodium excretion ≥ 4.0 g/day, assessed by repeated measurements of spot urine, is associated with composite cardiovascular (CV) events of heart failure (HF) hospitalization, acute coronary syndrome, cerebrovascular events, and documented CV deaths in Japanese high-risk patients with either stable and compensated congestive HF, high brain natriuretic peptide, coronary artery disease, cerebrovascular disease, chronic kidney disease, or atrial fibrillation. A total of 520 patients were enrolled. During the median follow-up period of 5.2 years, 105 (20%) experienced composite CV events, which were predominantly driven by 60 (12%) HF hospitalizations. The aim of the present study was to elucidate which subgroups of patients with high sodium excretion were associated with HF hospitalization. We divided the enrolled patients into three groups according to the amount of sodium excretion (< 3.0 g/day, 3.0-3.99 g/day (reference), and ≥ 4.0 g/day) based on a median of 14 measurements during follow-up. We assessed the hazard ratio for HF hospitalization according to age, bodyweight, and gender, using the Cox hazard model. In the total population, high sodium excretion ≥ 4.0 g/day was associated with HF hospitalization [hazard ratio (HR) 1.75, confidence interval (CI) 1.05-2.83] after adjustment for gender, age, and bodyweight, but was not associated with other CV events. In older patients (≥ 75 years old), high sodium excretion ≥ 4.0 g/day was associated with HF hospitalization after adjustment for gender and bodyweight (HR 3.25, CI 1.55-6.55), which was not observed in younger (< 75 years old) patients. In patients with lower bodyweight (< 60 kg), high sodium excretion ≥ 4.0 g/day was associated with HF hospitalization after adjustment for age and gender (HR 3.05, CI 1.34-6.61), which was not observed in heavier (≥ 60 kg) patients. High sodium excretion is associated with HF hospitalization in patients with older age and lower bodyweight in Japanese high-risk patients. 10.1007/s00380-020-01673-2
    Evaluating risk prediction models for adults with heart failure: A systematic literature review. Di Tanna Gian Luca,Wirtz Heidi,Burrows Karen L,Globe Gary PloS one BACKGROUND:The ability to predict risk allows healthcare providers to propose which patients might benefit most from certain therapies, and is relevant to payers' demands to justify clinical and economic value. To understand the robustness of risk prediction models for heart failure (HF), we conducted a systematic literature review to (1) identify HF risk-prediction models, (2) assess statistical approach and extent of validation, (3) identify common variables, and (4) assess risk of bias (ROB). METHODS:Literature databases were searched from March 2013 to May 2018 to identify risk prediction models conducted in an out-of-hospital setting in adults with HF. Distinct risk prediction variables were ranked according to outcomes assessed and incorporation into the studies. ROB was assessed using Prediction model Risk Of Bias ASsessment Tool (PROBAST). RESULTS:Of 4720 non-duplicated citations, 40 risk-prediction publications were deemed relevant. Within the 40 publications, 58 models assessed 55 (co)primary outcomes, including all-cause mortality (n = 17), cardiovascular death (n = 9), HF hospitalizations (n = 15), and composite endpoints (n = 14). Few publications reported detail on handling missing data (n = 11; 28%). The discriminatory ability for predicting all-cause mortality, cardiovascular death, and composite endpoints was generally better than for HF hospitalization. 105 distinct predictor variables were identified. Predictors included in >5 publications were: N-terminal prohormone brain-natriuretic peptide, creatinine, blood urea nitrogen, systolic blood pressure, sodium, NYHA class, left ventricular ejection fraction, heart rate, and characteristics including male sex, diabetes, age, and BMI. Only 11/58 (19%) models had overall low ROB, based on our application of PROBAST. In total, 26/58 (45%) models discussed internal validation, and 14/58 (24%) external validation. CONCLUSIONS:The majority of the 58 identified risk-prediction models for HF present particular concerns according to ROB assessment, mainly due to lack of validation and calibration. The potential utility of novel approaches such as machine learning tools is yet to be determined. REGISTRATION NUMBER:The SLR was registered in Prospero (ID: CRD42018100709). 10.1371/journal.pone.0224135
    Effect of the Creatinine Excretion Rate Index, a Marker of Sarcopenia, on Prediction of Intracranial Hemorrhage in Patients With Advanced Heart Failure and a Continuous-Flow Left Ventricular Assist Device. Iwasaki Keiichiro,Seguchi Osamu,Murata Shunsuke,Nishimura Kunihiro,Yoshitake Koichi,Yagi Nobuichiro,Sujino Yasumori,Anegawa Eiji,Mochizuki Hiroki,Kuroda Kensuke,Nakajima Seiko,Watanabe Takuya,Yanase Masanobu,Fukushima Satsuki,Fujita Tomoyuki,Kobayashi Junjiro,Ito Hiroshi,Fukushima Norihide Circulation journal : official journal of the Japanese Circulation Society BACKGROUND:Sarcopenia is characterized by progressive loss of skeletal muscle and has frequently been associated with poor clinical outcomes in patients with advanced heart failure (HF). The urinary creatinine excretion rate (CER) index is an easily measured marker of muscle mass, but its predictive capacity for mortality and cerebrovascular events has not been investigated in patients with a continuous-flow implantable left ventricular assist device (CF-iLVAD).Methods and Results:We retrospectively reviewed 147 patients (mean [±SD] age 43.7±12.5 years, 106 male) who underwent CF-iLVAD implantation between April 2011 and June 2019. CER indices in 24-h urine samples before CF-iLVAD implantation were determined. Over a median follow-up of 2.3 years, there were 10 (6.8%) deaths and 43 (29.3%) cerebrovascular events. Patients were divided into 2 groups (low and high CER index) according to the median CER index in men and women (i.e., 13.71 and 12.06 mg·kg·day, respectively). Mortality and intracranial hemorrhage rates after CF-iLVAD implantation were significantly higher in the low than high CER index group (mortality 12.3% vs. 1.4% [P<0.01]; intracranial hemorrhage 23.3% vs. 8.1% [P=0.01]). Multivariate Cox proportional hazard models revealed that a low CER index was an independent predictor of intracranial hemorrhage in patients receiving a CF-iLVAD (hazard ratio 3.63; 95% confidence interval 1.43-9.24; P<0.01). CONCLUSIONS:A low preoperative CER index is an independent, non-invasive predictor of intracranial hemorrhage after CF-iLVAD implantation. 10.1253/circj.CJ-19-0930
    Kidney Disease Biomarkers Improve Heart Failure Risk Prediction in the General Population. Nowak Christoph,Ärnlöv Johan Circulation. Heart failure BACKGROUND:The kidneys play an important role in heart failure (HF), but it is unclear if renal biomarkers improve HF risk prediction beyond established risk factors. We aimed to assess whether adding biomarkers of kidney disease to conventional risk factors improved 10-year risk prediction for incident HF in a contemporary community sample. METHODS:We included 450 212 participants in the UK Biobank aged 39 to 70 years without HF who had been assessed in 2006 to 2010 with the urine albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C. There were 1701 incident cases of HF during up to 10.3 years of follow-up (mean 8.2±0.7 years). We used the Atherosclerosis Risk in Communities study heart failure risk score excluding natriuretic peptides as the base model to which we added eGFR and urine albumin-to-creatinine ratio. Harrell's C-statistic of ARIC-HF was 0.845 (95% CI, 0.831-0.859). RESULTS:Each combination of added kidney measures (creat-eGFR, cysC-eGFR, and urine albumin-to-creatinine ratio) led to significant improvement in risk discrimination, calibration, and reclassification. The optimal pair of added kidney measures was cysC-eGFR and urine albumin-to-creatinine ratio (ΔC=0.019 [95% CI, 0.015-0.022]). Addition of cysC-eGFR made the largest contribution to reclassification improvement (continuous net reclassification improvement 0.323 [95% CI, 0.278-0.360]). CONCLUSIONS:In a large community sample, the addition of kidney disease markers to conventional risk factors improved prediction of 10-year HF risk. Our results support including kidney disease markers in the identification of persons at highest risk of HF and demonstrate a possible role of impaired kidney function in HF development in asymptomatic persons. 10.1161/CIRCHEARTFAILURE.120.006904
    Prediction of all-cause mortality with hypoalbuminemia in patients with heart failure: a meta-analysis. Peng Wenhua,Zhang Channa,Wang Zhijun,Yang Wenqi Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals The prognostic utility of serum albumin level for mortality in heart failure patients has received considerable attention. This meta-analysis sought to examine the prognostic significance of hypoalbuminemia for prediction of all-cause mortality in patients with heart failure. Pubmed and Embase databases were systematically searched up to 10 March 2019 to identify eligible studies. Epidemiological studies reporting a multivariable-adjusted risk estimate of all-cause mortality associated with hypoalbuminemia in acute or chronic heart failure patients were included. Nine studies from 10 articles involving 16,763 heart failure patients were included in the final analysis. Hypoalbuminemia was associated with an increased in-hospital mortality (risk ratio [RR] 4.90; 95% confidence interval [CI] 2.96-8.10) and long-term all-cause mortality (RR 1.75; 95% CI 1.35-2.27) in acute heart failure patients. Chronic heart failure patients with hypoalbuminemia exhibited a 3.5-fold (95% CI 1.29-9.73) higher risk for long-term all-cause mortality. Hypoalbuminemia is possibly an independent predictor of all-cause mortality in patients with acute or chronic heart failure. However, the current findings should be further confirmed in future prospective studies. Moreover, future well-designed randomized controlled trials would be required to investigate whether correcting hypoalbuminemia in heart failure patients has potential to improve survival outcome. 10.1080/1354750X.2019.1652686
    MicroRNA-423-5p as a biomarker for early diagnosis and outcome prediction of acute kidney injury in patients with acute decompensated heart failure. Zhang Hongmei,Liu Jiaolei,Li Xin,Wang Lin,Yu Huining,Huang Jiaohong,Liu Qingjun,Wang Chao,Jiang Aili International journal of urology : official journal of the Japanese Urological Association OBJECTIVE:To evaluate the clinical significance of serum and urinary microRNA-423-5p in the prediction of acute kidney injury onset and survival in patients with acute decompensated heart failure. METHODS:A total of 180 acute decompensated heart failure patients, including 57 acute kidney injury cases and 123 non-acute kidney injury cases, were included in this study. Serum and urinary neutrophil gelatinase-associated lipocalin, a biomarker of renal injury of acute kidney injury, was detected using an enzyme-linked immunosorbent assay. Expression of microRNA-423-5p in serum and urine samples was examined using quantitative real-time polymerase chain reaction. The clinical significance of microRNA-423-5p was evaluated using receiver operating characteristic curve and Kaplan-Meier survival analysis. RESULTS:The levels of neutrophil gelatinase-associated lipocalin and microRNA-423-5p in serum and urine samples were elevated in patients with acute kidney injury compared with the non-acute kidney injury cases (all P < 0.05). Serum and urinary microRNA-423-5p had relatively high predictive performance for acute kidney injury onset in acute decompensated heart failure patients, and this predictive value was more significant when combined with urinary neutrophil gelatinase-associated lipocalin. In addition, serum and urinary elevated levels of microRNA-423-5p predicted a poor 180-day survival in the acute kidney injury group. CONCLUSION:Increased serum and urinary microRNA-423-5p can predict the occurrence of acute kidney injury in acute decompensated heart failure patients, and is associated with poor survival of acute kidney injury patients. In addition, the diagnostic value of urine neutrophil gelatinase-associated lipocalin for the early screening of acute kidney injury from acute decompensated heart failure patients might be improved by considering the changes in urinary microRNA-423-5p. 10.1111/iju.14380
    Risk Scores and Prediction Models in Chronic Heart Failure: A Comprehensive Review. Toumpourleka Maria,Patoulias Dimitrios,Katsimardou Alexandra,Doumas Michael,Papadopoulos Christodoulos Current pharmaceutical design BACKGROUND:Heart failure affects a substantial proportion of the adult population, with an estimated prevalence of 1-2% in developed countries. Over the previous decades, many prediction models have been introduced for this specific population in an attempt to better stratify and manage heart failure patients. OBJECTIVE:The aim of this study is the systematic review of recent, relevant literature regarding risk scores or prediction models in ambulatory patients with an established diagnosis of chronic heart failure. METHODS:We conducted a systematic search of the literature in PubMed and CENTRAL from their inception up till December 2019 for studies assessing the performance of risk scores and prediction models and original research studies. Grey literature was searched as well. This review is reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. RESULTS:We included 16 eligible studies in this systematic review. Major heart failure risk scores derived from large heart failure populations were among the included studies. Due to significant heterogeneity regarding the main endpoints, a direct comparison of the included prediction scores was inevitable. The majority referred to patients with heart failure with reduced ejection fraction, while only two out of 16 prediction scores have been developed exclusively for heart failure patients with preserved ejection fraction. Ischemic heart disease was the most common aetiology of heart failure in the included studies. Finally, more than half of the prediction scores have not been externally validated. CONCLUSION:Prediction models aiming at heart failure patients with a preserved or mid-range ejection fraction are lacking. Prediction scores incorporating recent advances in pharmacotherapy should be developed in the future. 10.2174/1381612826666200521141249
    Do plasma neprilysin activity and plasma neprilysin concentration predict cardiac events in chronic kidney disease patients? Emrich Insa E,Vodovar Nicolas,Feuer Linda,Untersteller Kathrin,Nougue Helene,Seiler-Mussler Sarah,Fliser Danilo,Launay Jean-Marie,Heine Gunnar H Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Background:Since the introduction of sacubitril/valsartan in clinical cardiology, neprilysin has become a major target for heart failure treatment. Plasma neprilysin concentration has been discussed as a novel biomarker that predicts cardiac events. Natriuretic peptides may inhibit plasma neprilysin. As they accumulate in chronic kidney disease (CKD), we hypothesized that high plasma neprilysin loses its predictive role in CKD patients. Methods:We measured plasma levels of neprilysin concentration, neprilysin activity and brain natriuretic peptide (BNP) in 542 CKD G2-G4 patients within the CARE FOR HOMe study. Patients were followed for predefined endpoints of hospitalization for acute decompensated heart failure and incident atherosclerotic cardiovascular events. Results:During 5.1 ± 2.1 years, 63 patients had acute decompensated heart failure and 125 patients had incident atherosclerotic cardiovascular events. In both Kaplan-Meier and multivariate Cox regression analyses, high plasma BNP and low, rather than elevated, neprilysin activity predicted future hospitalization for acute decompensated heart failure; neprilysin concentration was not predictive. Furthermore, only BNP was an independent predictor of incident atherosclerotic cardiovascular events. Conclusions:In line with experimental studies, high natriuretic peptides may inhibit neprilysin activity in CKD. Therefore, high neprilysin activity and concentrations are not predictors of adverse cardiovascular outcome in CKD patients. Thus neprilysin inhibitors should be implemented with caution in patients with advanced CKD. 10.1093/ndt/gfy066
    Clinical Value of Natriuretic Peptides in Predicting Time to Dialysis in Stage 4 and 5 Chronic Kidney Disease Patients. Sundqvist Sofia,Larson Thomas,Cauliez Bruno,Bauer Fabrice,Dumont Audrey,Le Roy Frank,Hanoy Mélanie,Fréguin-Bouilland Caroline,Godin Michel,Guerrot Dominique PloS one BACKGROUND:Anticipating the time to renal replacement therapy (RRT) in chronic kidney disease (CKD) patients is an important but challenging issue. Natriuretic peptides are biomarkers of ventricular dysfunction related to poor outcome in CKD. We comparatively investigated the value of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as prognostic markers for the risk of RRT in stage 4 and 5 CKD patients, and in foretelling all-cause mortality and major cardiovascular events within a 5-year follow-up period. METHODS:Baseline plasma BNP (Triage, Biosite) and NT-proBNP (Elecsys, Roche) were measured at inclusion. Forty-three patients were followed-up during 5 years. Kaplan-Meier analysis, with log-rank testing and hazard ratios (HR), were calculated to evaluate survival without RRT, cardiovascular events or mortality. The independent prognostic value of the biomarkers was estimated in separate Cox multivariate analysis, including estimated glomerular filtration rate (eGFR), creatininemia and comorbidities. RESULTS:During the first 12-month follow-up period, 16 patients started RRT. NT-proBNP concentration was higher in patients who reached endpoint (3221 ng/L vs 777 ng/L, p = 0.02). NT-proBNP concentration > 1345 ng/L proved significant predictive value on survival analysis for cardiovascular events (p = 0.04) and dialysis within 60 months follow-up (p = 0.008). BNP concentration > 140 ng/L was an independent predictor of RRT after 12 months follow-up (p<0.005), and of significant predictive value for initiation of dialysis within 60 months follow-up. CONCLUSIONS:Our results indicate a prognostic value for BNP and NT-proBNP in predicting RRT in stage 4 and 5 CKD patients, regarding both short- and long-term periods. NT-proBNP also proved a value in predicting cardiovascular events. Natriuretic peptides could be useful predictive biomarkers for therapeutic guidance in CKD. 10.1371/journal.pone.0159914
    Effect of glomerular filtration rate impairment on diagnostic performance of neutrophil gelatinase-associated lipocalin and B-type natriuretic peptide as markers of acute cardiac and renal failure in chronic kidney disease patients. Donadio Carlo Critical care (London, England) INTRODUCTION:Cardio-renal syndromes are characterized by the impairment of cardiac and renal functions. Plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL), and plasma B-type natriuretic peptide (BNP) are markers of acute kidney injury (AKI) and heart failure (HF), respectively. METHODS:GFR (99mTc-DTPA), plasma BNP, and plasma and urinary concentrations of NGAL were measured in 310 clinically stable CKD patients, at functional stages from 1 to 5. Serum and urinary low-molecular-weight proteins cystatin C and β2-microglobulin, and urinary tubular enzymes were measured for comparison. Plasma BNP, NGAL, cystatin C and β2-microglobulin were measured also in 31 maintenance hemodialysis patients. RESULTS:Plasma NGAL increased with the reduction of GFR in CKD patients from stage 2. In the different CKD stages modest differences were found for BNP values. Urinary NGAL increased slightly but significantly in patients at CKD stages 4 and 5, similarly to urinary cystatin C and β2-microglobulin. In maintenance hemodialysis patients, plasma NGAL and BNP were markedly increased, and high-flux hemodialysis significantly decreased their plasma concentrations. CONCLUSIONS:Plasma NGAL increases markedly with the reduction in GFR, generating a very high number of false positive diagnoses of AKI in stable CKD patients. The grade of GFR impairment and the cause of kidney disease have a lower effect on urinary NGAL and on plasma BNP. In any case, specific reference values of NGAL and BNP should be used in chronic kidney disease patients, according to their functional stage, when assessing acute kidney injury, heart failure, and cardio-renal syndromes in patients with impaired GFR. 10.1186/cc13752
    Plasma B-type natriuretic peptide concentration is independently associated with kidney function decline in Japanese patients with chronic kidney disease. Yoshitomi Ryota,Nakayama Masaru,Sakoh Teppei,Fukui Akiko,Shikuwa Yui,Tominaga Mitsuhiro,Tsuchihashi Takuya,Tsuruya Kazuhiko,Kitazono Takanari Journal of hypertension BACKGROUND AND OBJECTIVE:The relationship between B-type natriuretic peptide (BNP) concentration and renal outcomes in patients with chronic kidney disease (CKD) remains unclear; therefore, it has not been determined whether BNP is related to renal outcomes, independent of cardiac parameters. This study was designed to clarify whether BNP concentration is associated with renal outcomes in CKD patients, independent of cardiac functional and structural alterations. METHODS:This prospective observational study included 372 consecutive patients with CKD. The renal endpoint was the composite of doubling of serum creatinine concentration and end-stage renal disease requiring dialysis. BNP concentrations were divided into quartiles. A Cox proportional hazards model was utilized to determine the risk factors for poor renal outcomes. RESULTS:During a median follow-up of 23.1 months, the renal endpoint was observed in 124 patients, including 14, 18, 37 and 55 patients in the first through fourth BNP quartiles, respectively. After adjustment for covariates, including cardiac parameters such as left atrial diameter, left ventricular mass index, left ventricular ejection fraction, and left ventricular hypertrophy, the hazard ratios (HRs) for renal outcomes became progressively higher for the second [HR, 1.50; 95% confidence interval (CI), 0.70-3.30), third (HR, 2.29; 95% CI, 1.11-4.91), and fourth (HR, 4.29; 95% CI, 2.05-9.39) BNP quartiles when compared with the lowest BNP quartile. CONCLUSION:Higher BNP levels were associated with adverse renal outcomes, independent of cardiac structure and function, suggesting that BNP may be a useful biomarker for exploring factors associated with kidney disease progression. 10.1097/HJH.0000000000000847
    Cardiac biomarkers of heart failure in chronic kidney disease. Han Xiaorong,Zhang Shuai,Chen Zhongbo,Adhikari Binay Kumar,Zhang Ying,Zhang Jin,Sun Jian,Wang Yonggang Clinica chimica acta; international journal of clinical chemistry Heart failure remains a continuing threat to patients with chronic kidney disease (CKD). Although various heart failure biomarkers have been applied for early detection, diagnosis and prognosis in CKD, these are easily affected by renal insufficiency thus limiting use in these patients. In this review, the major four groups of heart failure biomarkers are explored. These include those associated with: myocardial stretch, ie, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP) and mid-regional proatrial natriuretic peptide (MR-proANP); myocyte injury, ie, high-sensitivity troponin T (hsTnT), heart-type fatty acid-binding protein (H-FABP); fibrosis, matrix remodelling and inflammation, ie, soluble growth stimulating gene 2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15); and renal function, ie, neutrophil gelatinase-associated lipocalin (NGAL) kidney injury molecule-1 (KIM-1), cystatin C (CysC), urinary sodium and urinary albumin. This review highlights classic heart failure biomarkers with critical values adjusted to glomerular filtration rate, summarizes research progress of new heart failure biomarkers and future research directions. Because diagnostic and prognostic usefulness of a single time point biomarker is limited, biomarkers should be combined and monitored at multiple times for optimal clinical impact. 10.1016/j.cca.2020.07.040
    Effect Modification of Chronic Kidney Disease on the Association of Circulating and Imaging Cardiac Biomarkers With Outcomes. Gregg L Parker,Adams-Huet Beverley,Li Xilong,Colbert Gates,Jain Nishank,de Lemos James A,Hedayati S Susan Journal of the American Heart Association BACKGROUND:Cardiac troponin T and brain natriuretic peptide (BNP) are elevated in >50% of dialysis patients and are associated with poor outcomes. Few data investigated these associations in earlier chronic kidney disease (CKD). METHODS AND RESULTS:We studied whether CKD modified associations of elevated BNP, N-terminal-pro-BNP, high-sensitivity cardiac troponin T, coronary artery calcification, and left ventricular hypertrophy with all-cause death and cardiovascular death/events in 3218 multiethnic individuals followed for 12.5 years, and whether biomarkers added prognostic information to traditional cardiovascular risk factors in CKD. Of the cohort, 279 (9%) had CKD. There were 296 deaths and 218 cardiovascular deaths/events. Of non-CKD individuals, 7% died and 6% had cardiovascular death/event versus 32% and 30% of CKD participants, <0.001 for both. The interaction between BNP and CKD on death was significant (=0.01): the adjusted hazard ratio in CKD was 2.05, 95% CI (1.34, 3.14), but not significant in non-CKD, 1.04 (0.76, 1.41). CKD modified the association of high-sensitivity cardiac troponin T with cardiovascular death/event, adjusted hazard ratio 3.34 (1.56, 7.18) in CKD versus 1.65 (1.16, 2.35) in non-CKD, interaction =0.09. There was an interaction between N-terminal-pro-BNP and CKD for death in those without prior cardiovascular disease. Addition of each biomarker to traditional risk factors improved risk prediction, except coronary artery calcification was not discriminatory for cardiovascular death/event in CKD. CONCLUSIONS:Cardiac biomarkers, with the exception of coronary artery calcification, prognosticated outcomes in early-stage CKD as well as, if not better than, in non-CKD individuals, even after controlling for estimated glomerular filtration rate, and added to information obtained from traditional cardiovascular risk factors alone. 10.1161/JAHA.116.005235
    Prognostic Significance of Asymptomatic Brain Natriuretic Peptide Elevation at Nephrology Referral in Patients with Chronic Kidney Disease. Hayashi Terumasa,Yasuda Keiko,Kimura Tomonori,Sasaki Koichi,Shimada Karin,Hashimoto Nobuhiro,Isaka Yoshitaka American journal of nephrology BACKGROUND:It is unclear whether asymptomatic elevation of brain natriuretic peptide (BNP) is associated with cardiovascular events (CVEs) or heart failure (HF) in predialysis chronic kidney disease (CKD) patients. METHODS:We measured BNP in 482 asymptomatic predialysis patients with CKD stages 2-5 at nephrology referral between August 2004 and October 2010, and followed them prospectively to investigate the prognostic significance of BNP using Cox models and receiver operating characteristic (ROC) analyses. The primary composite end point was the time to death or the first nonfatal CVEs. Secondary end points included CVEs including sudden death, HF and all-cause death. RESULTS:The median age was 67 years (male, 67.4%; diabetic nephropathy, 33.4%), and estimated glomerular filtration rate was 20.1 mL/min/1.73 m2. The primary end point occurred in 92 patients. CVEs including sudden death, HF and all-cause death occurred in 66, 35, and 54 patients, respectively during a median follow-up period of 37.7 months. Multivariate analyses showed that BNP level was significantly associated with the primary end point (hazard ratio [HR] 1.241; 95% CI 1.020-1.511; p = 0.031), CVEs (HR 1.337; 95% CI 1.067-1.675; p = 0.012) and HF (HR 1.489; 95% CI 1.059-2.091; p = 0.022), but not associated with all-cause death (HR 1.081; 95% CI 0.829-1.410; p = 0.565). The ROC curves showed that the optimal predictive BNP levels for the primary end point, CVEs and HF were 92.5, 127.0, and 274.6 (pg/mL) respectively. CONCLUSION:Asymptomatic elevation of BNP is strongly predictive for CVEs and HF, which might help to integrate cardio-renal risk stratification in predialysis CKD patients. 10.1159/000492724
    Impact of High-Cut-Off Dialysis on Renal Recovery in Dialysis-Dependent Multiple Myeloma Patients: Results from a Case-Control Study. Gerth Hans U,Pohlen Michele,Görlich Dennis,Thölking Gerold,Kropff Martin,Berdel Wolfgang E,Pavenstädt Hermann,Brand Marcus,Kümpers Philipp PloS one BACKGROUND:High-cut-off hemodialysis (HCO-HD) can effectively reduce high concentrations of circulating serum free light chains (sFLC) in patients with dialysis-dependent acute kidney injury (AKI) due to multiple myeloma (MM). Therefore, the aim of this study was to analyze renal recovery in a retrospective single-center cohort of dialysis-dependent MM patients treated with either conventional HD (conv. HD) or HCO-HD. METHODS AND RESULTS:The final cohort consisted of 59 patients treated with HCO-HD (n = 42) or conv. HD (n = 17). A sustained sFLC response was detected in a significantly higher proportion of HCO-HD patients (83.3%) compared with conv. HD patients (29.4%; p = 0.007). The median duration of sFLC required to reach values <1000 mg/l was 14.5 days in the HCO-HD group and 36 days in the conv. HD group. The corresponding rates of renal recovery were 64.3% and 29.4%, respectively (chi-squared test, p = 0.014). Multivariate regression and decision tree analysis (recursive partitioning) revealed HCO-HD (adjusted odds ratio [OR] 6.1 [95% confidence interval (CI) 1.5-24.5], p = 0.011) and low initial uric acid values (adjusted OR 1.3 [95%CI 1.0-1.7], p = 0.045) as independent and paramount variables associated with a favorable renal outcome. CONCLUSIONS:In summary, the results from this retrospective case-control study suggest in addition to novel agent-based chemotherapy a benefit of HCO-HD in sFLC removal and renal outcome in dialysis-dependent AKI secondary to MM. This finding was especially pertinent in patients with low initial uric acid values, resulting in a promising renal recovery rate of 71.9%. Further prospective studies are warranted. 10.1371/journal.pone.0154993
    Management of acute kidney injury in symptomatic multiple myeloma. Bridoux Frank,Leung Nelson,Belmouaz Mohamed,Royal Virginie,Ronco Pierre,Nasr Samih H,Fermand Jean Paul, Kidney international Symptomatic multiple myeloma is commonly complicated by acute kidney injury through various mechanisms. The most frequent is the precipitation of monoclonal free light chains with uromodulin in the distal tubules, defining light chain cast nephropathy. Early diagnosis and identification of the cause of acute kidney injury are required for optimizing management and avoiding chronic kidney injury that strongly affects quality of life and patient survival. In light chain cast nephropathy, often manifesting with severe acute kidney injury, renal recovery requires urgent intervention based on vigorous rehydration, correction of precipitating factors, and efficient anti-plasma cell chemotherapy to rapidly reduce the secretion of nephrotoxic free light chains. Currently, the association of the proteasome inhibitor bortezomib with high-dose dexamethasone is the standard regimen in newly diagnosed patients. The addition of another drug such as cyclophosphamide or an immunodulatory agent may improve free light chain response but raises tolerance concerns in frail patients. Further studies are warranted to confirm the role of anti-CD38 monoclonal antibodies, whose efficacy and tolerance have been documented in patients without renal impairment. Despite controversial results from randomized studies, recent data suggest that in patients with light chain cast nephropathy and acute kidney injury requiring dialysis, the combination of chemotherapy with free light chain removal through high-cutoff hemodialysis may increase renal response recovery rates. Kidney biopsy may be helpful in guiding management and assessing renal prognosis that appears to depend on the extent of cast formation and interstitial fibrosis/tubular atrophy. Because of continuous improvement in life expectancy of patients with multiple myeloma, renal transplantation is likely to be increasingly considered in selected candidates. 10.1016/j.kint.2020.11.010
    [Expert consensus for the diagnosis and treatment of patients with renal impairment of multiple myeloma]. Zhonghua nei ke za zhi Renal impairment (RI) is a common complication of multiple myeloma (MM), which is presented as chronic kidney disease (CKD) or acute kidney injury (AKI). The typical pathological feature is cast nephropathy. Presently international system staging (ISS) is used in evaluating MM. Although the classic Durie-Salmon staging system could be still used in clinical practice, it may miss out some patients with renal impairment. For evaluations of RI in MM patients with CKD, it's recommended to assess the estimated glomerular filtration rate (eGFR) by creatinine based formula CKD-epidemiology collaboration (EPI) or modification of diet in renal disease(MDRD) and to stage the renal injuries according to 2013 Kidney Disease Improving Global Outcomes (KDIGO) CKD guidelines. For MM patients with AKI, KDIGO AKI guidelines is recommended for evaluation. Renal biopsy is not a routine procedure in all MM patients. It's necessary for patients presenting with glomerular injuries such as albuminuria > 1 g/24 h to eliminate immunoglobulin associated amyloidosis (AL) and monoclonal immunoglobulin deposition disease (MIDD). The effective treatment of MM can reduce serum light chain concentration and improve renal function. The basis of the RI treatment in MM is bortizomib-based regimen, which does not require dosage adjustment in patients with dialysis or renal insufficiency. Thalidomide and lenalidomide are two major immunomodulators in MM treatment. Thalidomide can be used effectively in RI patients without dosage adjustment while lenalidomide should be used cautiously in patients with mild or moderate RI with dosage adjustment and serum toxicity surveillance. High-dose therapy (HDT) and autologous peripheral blood stem cell transplantation (APBSCT) can be therapeutical options for RI patients younger than 65 y, and they should be considered more prudently in patients with severe renal insufficiency (GFR<30 ml/min). For patients who are not suitable for the treatment mentioned above, they can be treated with conventional chemotherapy, including VAD (vincristine, adriamycin and dexamethasone), MP (mephalan and prednisolone) and high-dose dexamethasone regimen. Adequate hydration (at least 3 litres of fluid intake a day or 2 L·m(-2)·d(-1)) and correcting reversible causes of RI are key points for the supportive care. Renal replacement therapy (more often hemodialysis) should be started in patients with severe AKI and end stage renal disease (ESRD). High flux or high cut-off membrane are recommended because routine hemodialysis could not remove the serum free light chain (sFLC) effectively. Plasmapheresis (PE) is recommended for patients with hyperviscosity syndrome or cast nephropathy presented with AKI, which may help to increase the dialysis-independency. 10.3760/cma.j.issn.0578-1426.2017.11.022
    Effect factors related to a high probability of hemodialysis independence in newly diagnosed multiple myeloma patients requiring hemodialysis. Song Jia,Jiang Fengjuan,Liu Hui,Ding Kai,Ren Yue,Li Lijuan,Wang Guojin,Shao Zonghong,Fu Rong Journal of clinical laboratory analysis BACKGROUND:Renal failure is a severe complication of symptomatic myeloma, related to higher mortality. Recovery from dialysis dependence can lead to enormous survival benefits. We investigated the effect factors for probability of dialysis independence. METHODS:Retrospective data on 45 newly diagnosed MM (NDMM) patients with serious renal impairment and requiring hemodialysis were analyzed. The statistical methods including logistic regression analysis, Kaplan-Meier survival curves, the log-rank test and the Cox proportional hazards model for survival analysis were used in our study. RESULTS:Twenty-two of the 45 patients, who were on hemodialysis at diagnosis, became dialysis independence. In the logistic regression analysis, serum level of β2-microglobulin, kidney disease history, involved free light chain, and achieving at least VGPR were significantly associated with reversibility from dialysis dependence. In addition, achieving hemodialysis discontinuation was related to better survival. The multivariate analyses demonstrated that reversibility from dialysis dependence, proteinuria < 3.5 g/24 h, and achieving at least VGPR were significantly associated with OS among NDMM patients requiring hemodialysis. CONCLUSION:Lower serum level of β2-microglobulin and lower level of free light chain at diagnosis, achieving at least VGPR, and shorter kidney disease history are related to a high probability of dialysis independence in NDMM patients with serious renal failure requiring dialysis. 10.1002/jcla.23057
    N-Terminal Fragment of Brain-Type Natriuretic Peptide (NT-proBNP) as a Prognostic Marker in Patients with Newly Diagnosed Multiple Myeloma Complicated by Dialysis-Dependent Renal Failure. Semochkin S V,Misyurina E N,Zhelnova E I,Yurova E V,Gagloeva D E,Aref'eva N A,Ushakova A I,Kotenko O N,Tolstykh T N,Sinyavkin D O,Baryakh E A,Yatskov K V,Samsonova I V,Lysenko M A Bulletin of experimental biology and medicine Prognostic value of N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) was analyzed in patients with multiple myeloma complicated by dialysisdependent renal failure. The prospective study included 20 patients with newly diagnosed multiple myeloma. The concentrations of NT-proBNP were measured before antimyeloma chemotherapy. The median age of the patients was 67 (63-76) years. The median glomerular filtration rate was 4 (4, 5) ml/min/1.73 m. For overall survival, the area under ROC curve was 0.75 and the cut-off point was 7000 pg/ml. At median follow-up of 17.3 months, the overall survival was 76.6±14.8 and 27.3±13.4% (p=0.02) for cases with NT-proBNP levels below and above the cut-off point, respectively. There were no cases of death due to cardiovascular causes. We concluded that the increase in serum concentration of NT-proBNP>7400 pg/ml is associated with the severity of kidney damage and the risk of non-cardiac mortality. 10.1007/s10517-019-04506-z
    An Inverse Relationship between Hyperuricemia and Mortality in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis. Lai Kuan-Ju,Kor Chew-Teng,Hsieh Yao-Peng Journal of clinical medicine The results have been inconsistent with regards to the impact of uric acid (UA) on clinical outcomes both in the general population and in patients with chronic kidney disease. The aim of this study was to study the influence of serum UA levels on mortality in patients undergoing continuous ambulatory peritoneal dialysis. Data on 492 patients from a single peritoneal dialysis unit were retrospectively analyzed. The mean age of the patients was 53.5 ± 15.3 years, with 52% being female ( = 255). The concomitant comorbidities at the start of continuous ambulatory peritoneal dialysis (CAPD) encompassed diabetes mellitus ( = 179, 34.6%), hypertension ( = 419, 85.2%), and cardiovascular disease ( = 186, 37.9%). The study cohort was divided into sex-specific tertiles according to baseline UA level. A Cox proportional hazard model was used to calculate hazard ratios (HRs) of all-cause, cardiovascular, and infection-associated mortality with adjustments for demographic and laboratory data, medications, and comorbidities. Multivariate Cox regression analysis showed that, using UA tertile 1 as the reference, the adjusted HR of all-cause, cardiovascular, and infection-associated mortality for tertile 3 was 0.4 (95% confidence interval (CI) 0.24⁻0.68, = 0.001), 0.4 (95% CI 0.2⁻0.81, = 0.01), and 0.47 (95% CI 0.19⁻1.08, = 0.1). In the fully adjusted model, the adjusted HRs of all-cause, cardiovascular, and infection-associated mortality for each 1-mg/dL increase in UA level were 0.84 (95% CI, 0.69⁻0.9, = 0.07), 0.79 (95% CI, 0.61⁻1.01, = 0.06), and 0.79 (95% CI, 0.48⁻1.21, = 0.32) for men and 0.57 (95% CI, 0.44⁻0.73, < 0.001), 0.6 (95% CI, 0.41⁻0.87, = 0.006), and 0.41 (95% CI, 0.26⁻0.6, < 0.001) for women, respectively. Higher UA levels are associated with lower risks of all-cause, cardiovascular and infection-associated mortality in women treated with continuous ambulatory peritoneal dialysis. 10.3390/jcm7110416
    Glycated Albumin versus Glycated Hemoglobin as a Glycemic Indicator in Diabetic Patients on Peritoneal Dialysis. Kobayashi Hiroki,Abe Masanori,Yoshida Yoshinori,Suzuki Hiroko,Maruyama Noriaki,Okada Kazuyoshi International journal of molecular sciences Compared with glycated hemoglobin (HbA1c), glycated albumin (GA) is superior in estimating glycemic control in diabetic patients on hemodialysis (HD). However, the better index for assessment of glycemic control in diabetic patients on peritoneal dialysis (PD) and the impact of protein loss on GA are unknown. Twenty diabetic patients on HD were matched by age, sex, and baseline postprandial plasma glucose (PG) levels to 20 PD patients. PG, HbA1c, GA, and serum albumin levels were measured for six months. Protein loss in PD patients was estimated by measuring the protein concentration in the peritoneal dialysate and by 24 h urine collection. Although PG and HbA1c did not differ significantly between the groups, the PD group had significantly lower GA (17.8% versus 20.8%, p < 0.001) and GA/HbA1c ratio (2.95% versus 3.45%, p < 0.0001) than the HD group. Although the PG level correlated significantly with the GA levels in both groups, it was not correlated with the HbA1c levels in both groups. HbA1c level was negatively associated with erythropoiesis-stimulating agent (ESA) dose in both groups, whereas GA was not significantly associated with serum albumin, hemoglobin concentration, ESA dose, and protein loss. Multiple regression analysis identified GA as the only independent factor associated with PG in PD patients. Our results suggested that GA was not significantly associated with protein loss, hemoglobin, serum albumin, and ESA dose. Although GA might underestimate glycemic status, it provided a significantly better measure for estimating glycemic control than HbA1c, even in PD patients. 10.3390/ijms17050619
    Peritoneal Dialysis Can Be an Option for Dominant Polycystic Kidney Disease: an Observational Study. Janeiro Darío,Portolés Jose,Tato Ana María,López-Sánchez Paula,Del Peso Gloria,Rivera Maite,Castellano Inés,Fernández-Reyes Maria J,Pérez-Gómez Vanessa,Ortega Mayra,Martínez-Miguel Patricia,Felipe Carmen,Caparrós Guadalupe,Ortiz Alberto,Selgas Rafael, Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis BACKGROUND:Autosomal dominant polycystic kidney disease (ADPKD) has been considered a relative contraindication for peritoneal dialysis (PD), although there are few specific studies available. METHODS:A multicenter historical prospective matched-cohort study was conducted to describe the outcome of ADPKD patients who have chosen PD. All ADPKD patients starting PD (n = 106) between January 2003 and December 2010 and a control group (2 consecutive patients without ADPKD) were studied. Mortality, PD-technique failure, peritonitis, abdominal wall leaks and cyst infections were compared. RESULTS:Patients with ADPKD had similar age but less comorbidity at PD inclusion: Charlson comorbidity index (CCI) 4.3 (standard deviation [SD] 1.6) vs 5.3 (SD 2.5) p < 0.001, diabetes mellitus 5.7% vs 29.2%, p < 0.001 and previous cardiovascular events 10.4% vs 27.8%, p < 0.001. No differences were observed in clinical events that required transient transfer to hemodialysis, nor in peritoneal leakage episodes or delivered dialysis dose. The cyst infection rate was low (0.09 episodes per patient-year) and cyst infections were not associated to peritonitis episodes. Overall technique survival was similar in both groups. Permanent transfer to hemodialysis because of surgery or peritoneal leakage was more frequent in ADPKD. More ADPKD patients were included in the transplant waiting list (69.8 vs 58%, p = 0.04) but mean time to transplantation was similar (2.08 [1.69 - 2.47] years). The mortality rate was lower (2.5 vs 7.6 deaths/100 patient-year, p = 0.02) and the median patient survival was longer in ADPKD patients (6.04 [5.39 - 6.69] vs 5.57 [4.95 - 6.18] years, p = 0.024). CONCLUSION:Peritoneal dialysis is a suitable renal replacement therapy option for ADPKD patients. 10.3747/pdi.2014.00029
    Total Bilirubin in Prognosis for Mortality in End-Stage Renal Disease Patients on Peritoneal Dialysis Therapy. Yang Tsung-Lin,Lin Yi-Chun,Lin Yen-Chung,Huang Chun-Yao,Chen Hsi-Hsien,Wu Mai-Szu Journal of the American Heart Association BACKGROUND:Evidence regarding bilirubin's antioxidant properties and predictive roles is growing. However, it is unclear whether serum bilirubin would have a prognostic impact on survival of patients with regular peritoneal dialysis. METHODS AND RESULTS:We used the Taiwan Renal Registry Data System utilizing its 2005-2012 data set. Data from patients on regular peritoneal dialysis were retrieved. The primary end point of observation was 3-year mortality. A total of 3704 patients (mean age 53.5 years, 44% male) were enrolled, and these patients were divided according to baseline serum total bilirubin levels (<0.3, 0.3-0.4, 0.4-0.5, 0.5-0.6, >0.6 mg/dL). Serum total bilirubin level was linearly related to age, incidence of hypertension, and type 2 diabetes mellitus. At the end of the observation period with a mean follow-up of 2.12±1.07 years, 1095 (30.6%) deaths were detected. Serum total bilirubin level and 3-year mortality rate presented a U-shaped relationship. Those with serum total bilirubin 0.5 to 0.6 mg/dL had the lowest 3-year mortality rate (24%). After adjustment for age, sex, underlying systemic disorders, medications, and laboratory discrepancies, serum total bilirubin still played an independent role for predicting 3-year mortality. CONCLUSIONS:Baseline serum total bilirubin level is significantly associated with 3-year mortality among patients receiving regular peritoneal dialysis. 10.1161/JAHA.117.007507
    Insulin Resistance in Nondiabetic Peritoneal Dialysis Patients: Associations with Body Composition, Peritoneal Transport, and Peritoneal Glucose Absorption. Bernardo Ana Paula,Oliveira Jose C,Santos Olivia,Carvalho Maria J,Cabrita Antonio,Rodrigues Anabela Clinical journal of the American Society of Nephrology : CJASN BACKGROUND AND OBJECTIVES:Insulin resistance has been associated with cardiovascular disease in peritoneal dialysis patients. Few studies have addressed the impact of fast transport status or dialysis prescription on insulin resistance. The aim of this study was to test whether insulin resistance is associated with obesity parameters, peritoneal transport rate, and glucose absorption. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Insulin resistance was evaluated with homeostasis model assessment method (HOMA-IR), additionally corrected by adiponectin (HOMA-AD). Enrolled patients were prevalent nondiabetics attending at Santo António Hospital Peritoneal Dialysis Unit, who were free of hospitalization or infectious events in the previous 3 months (51 patients aged 50.4 ± 15.9 years, 59% women). Leptin, adiponectin, insulin-like growth factor-binding protein 1 (IGFBP-1), and daily glucose absorption were also measured. Lean tissue index, fat tissue index (FTI), and relative fat mass (rel.FM) were assessed using multifrequency bioimpedance. Patients were categorized according to dialysate to plasma creatinine ratio at 4 hours, 3.86% peritoneal equilibration test, and obesity parameters. RESULTS:Obesity was present in 49% of patients according to rel.FM. HOMA-IR correlated better with FTI than with body mass index. Significant correlations were found in obese, but not in nonobese patients, between HOMA-IR and leptin, leptin/adiponectin ratio (LAR), and IGFBP-1. HOMA-IR correlated with HOMA-AD, but did not correlate with glucose absorption or transport rate. There were no significant differences in insulin resistance indices, glucose absorption, and body composition parameters between fast and nonfast transporters. A total of 18 patients (35.3%) who had insulin resistance presented with higher LAR and rel.FM (7.3 [12.3, interquartile range] versus 0.7 [1.4, interquartile range], P<0.001, and 39.4 ± 10.1% versus 27.2 ± 11.5%, P=0.002, respectively), lower IGFBP-1 (8.2 ± 7.2 versus 21.0 ± 16.3 ng/ml, P=0.002), but similar glucose absorption and small-solute transport compared with patients without insulin resistance. FTI and LAR were independent correlates of HOMA-IR in multivariate analysis adjusted for glucose absorption and small-solute transport (r=0.82, P<0.001). CONCLUSIONS:Insulin resistance in nondiabetic peritoneal dialysis patients is associated with obesity and LAR independent of glucose absorption and small-solute transport status. Fast transport status was not associated with higher likelihood of obesity or insulin resistance. 10.2215/CJN.03170315
    End-Stage Renal Disease Patients with Low Serum Albumin: Is Peritoneal Dialysis an Option? Singh Tripti,Astor Brad C,Waheed Sana Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis Low serum albumin is associated with high mortality in patients with end-stage renal disease (ESRD) on chronic dialysis. Clinicians are reluctant to offer peritoneal dialysis (PD) as an option for dialysis for patients with low serum albumin due to concerns of loss of albumin with PD, but evidence supporting differences in outcomes is limited. We evaluated mortality based on dialysis modality in patients with very low serum albumin (< 2.5 g/dL).We analyzed United States Renal Data System (USRDS) data from 2010 to 2015 to assess mortality by modality adjusted for age, sex, race, employment, number of comorbidities, and year of dialysis initiation.Low serum albumin (< 2.5 g/dL) was present in 78,625 (19.9%) of 395,656 patients with ESRD on chronic dialysis. Patients with low serum albumin were less likely to use PD as their first modality than those with higher albumin (3.1% vs 10.9%; < 0.001). Use of PD was associated with lower mortality compared with hemodialysis (HD) (hazard ratio [HR] = 0.88, 95% confidence interval [CI] 0.81 - 0.95, < 0.05) in patients with low serum albumin. This difference was more pronounced in patients who had glomerulonephritis (HR = 0.72) or hypertension (HR = 0.81) than in those with end-stage renal disease (ESRD) due to diabetes mellitus or other causes.Peritoneal dialysis is less likely to be the first dialysis modality in patients with low serum albumin requiring dialysis. However, PD is associated with lower mortality than HD in patients with low serum albumin on dialysis. We recommend advocating the use of PD in patients with low serum albumin. 10.3747/pdi.2018.00204
    Obese and diabetic patients with end-stage renal disease: Peritoneal dialysis or hemodialysis? Ekart Robert,Hojs Radovan European journal of internal medicine Obesity is a chronic disease that is increasingly prevalent around the world and is a well-recognized risk factor for type 2 diabetes and hypertension, leading causes of end-stage renal disease (ESRD). The obese diabetic patient with ESRD is a challenge for the nephrologist with regard to the type of renal replacement therapy that should be suggested and offered to the patient. There is no evidence that either peritoneal dialysis or hemodialysis is contraindicated in obese ESRD patients. In the literature, we can find a discrepancy in the impact of obesity on mortality among hemodialysis vs. peritoneal dialysis patients. Several studies in hemodialysis patients suggest that a higher BMI confers a survival advantage - the so-called "reverse epidemiology". In contrast, the literature among obese peritoneal dialysis patients is inconsistent, with various studies reporting an increased risk of death, no difference, or a decreased risk of death. Many of these studies only spanned across a few years, and this is probably too short of a time frame for a realistic assessment of obesity's impact on mortality in ESRD patients. The decision for dialysis modality in an obese diabetic patient with ESRD should be individualized. According to the results of published studies, we cannot suggest PD or HD as a better solution for all obese diabetic patients. The obese patient should be educated about all their dialysis options, including home dialysis therapies. In this review, the available literature related to the dialysis modality in obese patients with diabetes and ESRD was reviewed. 10.1016/j.ejim.2016.03.016
    Use of continuous glucose monitoring in patients with diabetes on peritoneal dialysis: poor correlation with HbA1c and high incidence of hypoglycaemia. Oei E,Samad N,Visser A,Chowdhury T A,Fan S L Diabetic medicine : a journal of the British Diabetic Association BACKGROUND:Achieving adequate glycaemic control in patients with diabetes on peritoneal dialysis is challenging. Traditional assessment of glycaemia using HbA1c is difficult in such patients because of renal anaemia or carbamylation of haemoglobin, and significant glucose excursions may be masked. We describe three patients with diabetes on peritoneal dialysis with similar HbA1c levels, but with very different glucose profiles shown on continuous glucose monitoring. CASE REPORTS:Patient 1 was treated with gliclazide, and had a number of solutions with high glucose concentration in his dialysis prescription. Continuous glucose monitoring showed glucose levels > 11 mmol/l for > 17 h per day, and < 4 mmol/l for 72 min per day with no symptoms. His HbA1c level was 61 mmol/mol (7.7%). Patient 2 was treated with insulin. Continuous glucose monitoring showed glucose levels > 11 mmol/mol for 3.8 h per day, and < 4 mmol/mol for 3.8 h per day. His HbA1c level was 59 mmol/mol (7.6%). Patient 3 was treated with pioglitazone and gliclazide, and glucose levels were > 11 mmol/l for 8 h per day and < 4 mmol/l for 1.6 h per day. His HbA1c was 62 mmol/mol (7.8%). None of the patients was aware of hypoglycaemia during the periods of low glucose recorded on continuous glucose monitoring. CONCLUSION:Despite similar HbA1c levels, our three patients had very different glucose profiles. These cases highlight the fact that HbA1c is frequently inadequate in reflecting glucose control in patients with diabetes on peritoneal dialysis, and we suggest that intermittent continuous glucose monitoring may allow safer management of glycaemia in such patients. 10.1111/dme.12988
    Hemoglobin A1c in patients on peritoneal dialysis: how should we interpret it? Coelho Silvia,Rodrigues Anabela Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy Almost half the patients on peritoneal dialysis are diabetic and glycemic control is essential to improve both patient and technique survival. Hemoglobin A1c (HbA1c) is widely used in the general population for diabetes diagnosis and monitoring as it highly correlates with blood glucose levels and outcomes. Its use has been extrapolated to the peritoneal dialysis population, despite HbA1c being commonly underestimated. In renal failure patients, HbA1c is influenced by variables affecting not only glycemia but also hemoglobin and the time of interaction between the two. Importantly, the impact of these variables differs in peritoneal dialysis compared to non-dialysis chronic kidney disease and hemodialysis patients. Although HbA1c in peritoneal dialysis patients is less directly associated with blood glucose levels than in the general population, studies have confirmed its association with patient mortality. In this paper we review the variables that can influence HbA1c value emphasizing their impact in peritoneal dialysis patients. By providing clinicians with a comprehensive understanding of HbA1c results, we provide them with tools for a better patient management care and potential improved outcomes of peritoneal dialysis patients. 10.1111/1744-9987.12166
    Effect of diabetes on incidence of peritoneal dialysis-associated peritonitis. Ueda Risa,Nakao Masatsugu,Maruyama Yukio,Nakashima Akio,Yamamoto Izumi,Matsuo Nanae,Tanno Yudo,Ohkido Ichiro,Ikeda Masato,Yamamoto Hiroyasu,Yokoyama Keitaro,Yokoo Takashi PloS one BACKGROUND:Several reports on patients with diabetes mellitus (DM) treated by peritoneal dialysis (PD) have shown a higher risk of PD-associated peritonitis compared to non-DM (NDM) patients. The aim of this study was to investigate the incidence of PD-associated peritonitis in DM patients. METHODS:We divided all patients who received PD at a single center between January 1980 and December 2012 into three groups according to era: Period 1 (n = 43, 1980-1993); Period 2 (n = 123, 1994-2004); and Period 3 (n = 207, 2005-2012). We investigated incidences of PD-associated peritonitis between patients with and without DM. RESULTS:In Periods 1 and 2, incidence of PD-associated peritonitis was higher in the DM group than in the NDM group (P<0.05). However, no difference according to presence of DM was seen in Period 3. Multivariate Cox regression analysis revealed DM as a risk factor for incidence of PD-associated peritonitis in Periods 1 and 2, but not in Period 3 (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.15 to 5.23; HR, 2.36; 95%CI, 1.13 to 4.58; and HR, 0.82; 95%CI, 0.41 to 1.54, respectively). Furthermore, the peritonitis-free period was significantly shorter in the DM group than in the DM group in Periods 1 and 2, whereas no significant difference was seen in Period 3 (P<0.01, P<0.01 and P = 0.55, respectively). Moreover, a significant interaction was seen between diabetes and study period, and became less pronounced during Period 3(P<0.01). CONCLUSIONS:The increased risk of peritonitis in diabetics reported in previous periods has not been evident in recent years. 10.1371/journal.pone.0225316
    Efficacy of continuous erythropoietin receptor activator for end-stage renal disease patients with renal anemia before and after peritoneal dialysis initiation. Fujimoto Daisuke,Adachi Masataka,Miyasato Yoshikazu,Hata Yusuke,Inoue Hideki,Oda Akira,Kakizoe Yutaka,Nakagawa Terumasa,Shimasaki Akiko,Nakamura Keishi,Nagayoshi Yu,Mukoyama Masashi Clinical and experimental nephrology BACKGROUND:Serial management of renal anemia using continuous erythropoietin receptor activator (CERA) throughout the peritoneal dialysis initiation period has rarely been reported. We investigated the efficacy and dosage of CERA treatment from pre- to post-peritoneal dialysis initiation for anemia management in patients with end-stage renal disease. METHODS:Twenty-six patients (13 men; mean age 60.9 years) who started peritoneal dialysis between April 2012 and April 2018 were investigated. Serial changes in hemoglobin levels, transferrin saturation and ferritin levels, CERA dosage, and the erythropoietin resistance index (ERI) over a 48 week period were retrospectively examined. RESULTS:Mean hemoglobin levels increased significantly from 10.5 g/dL at 24 weeks prior to the peritoneal dialysis initiation to 11.5 g/dL at 4 weeks post-initiation. The proportion of patients with hemoglobin levels ≥ 11 g/dL increased significantly after peritoneal dialysis initiation. The mean CERA dosage was 57.0 µg/month at 24 weeks prior to dialysis initiation, 86.5 µg/month at initiation, and 72.0 µg/month at 4 weeks post-initiation. Thus, the dosage tended to increase immediately before peritoneal dialysis initiation and then decreased thereafter. Hemoglobin levels were significantly lower, while the CERA dosage for maintaining hemoglobin levels and ERI tended to be higher at dialysis initiation in patients with diabetes than in those without diabetes. CONCLUSION:Treatment with CERA prior to and during the peritoneal dialysis initiation achieved fairly good anemia management in patients with and without diabetes. The CERA dosage could be reduced in patients without diabetes after dialysis initiation. 10.1007/s10157-020-01973-x
    Glycemic control and survival in peritoneal dialysis patients with diabetes: A 2-year nationwide cohort study. Abe Masanori,Hamano Takayuki,Hoshino Junichi,Wada Atsushi,Nakai Shigeru,Masakane Ikuto Scientific reports For glycemic control in patients with diabetes on peritoneal dialysis (PD), the level of glycated albumin (GA) associated with mortality is unclear. Accordingly, we examined the difference in the association of GA and glycated hemoglobin (HbA1c) with 2-year mortality in a Japanese Society for Dialysis Therapy cohort. We examined 1601 patients with prevalent diabetes who were on PD. Of these, 1282 had HbA1c (HbA1c cohort) and 725 had GA (GA cohort) measured. We followed them for 2 years from 2013 to 2015 and used Cox regression to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for 2-year mortality after adjusting for potential confounders in each cohort. No significant association was found between HbA1c levels and all-cause death HRs before and after adjustment for confounders in the HbA1c cohort. In contrast, the adjusted all-cause death HRs and 95% CIs for GAs < 12.0%, 12.0-13.9%, 16.0-17.9%, 18.0-19.9%, 20.0-21.9%, and ≥22.0%, compared with 14.0-15.9% (reference), were 1.56 (0.32-7.45), 1.24 (0.32-4.83), 1.32 (0.36-4.77), 2.02 (0.54-7.53), 4.36 (1.10-17.0), and 4.10 (1.20-14.0), respectively. In the GA cohort, GA ≥ 20.0% was significantly associated with a higher death HR compared with the reference GA. Thus, GA ≥ 20.0% appears to be associated with a decrease in survival in diabetic patients on PD. There were no associations between HbA1c levels and 2-year mortality in PD patients. 10.1038/s41598-019-39933-5
    Rate of the "burnt-out diabetes" phenomenon in patients on peritoneal dialysis. Abe Masanori,Hamano Takayuki,Hoshino Junichi,Wada Atsushi,Nakai Shigeru,Masakane Ikuto Diabetes research and clinical practice AIMS:In some diabetes patients on dialysis, glycemic control improves spontaneously, leading to normal HbA1c levels; this phenomenon is known as "burnt-out diabetes." Glycated albumin (GA) might be a better indicator of glycemic control than HbA1c in hemodialysis patients, but it has not been assessed in peritoneal dialysis (PD) patients. METHODS:This study involved diabetes patients on PD, with HbA1c level and antidiabetes therapy records. First, the "burnt-out diabetes" phenomenon was investigated in patients with HbA1c measurements alone (HbA1c cohort). Then, it was investigated in patients with both HbA1c and GA measurements (GA cohort). RESULTS:A total of 1296 patients were included in the HbA1c cohort. When "burnt-out diabetes" was defined as HbA1c < 6.0% without treatment, it was noted in 269 patients (20.8%). A total of 413 patients were subsequently included in the GA cohort. "Burnt-out diabetes," using the same definition, was found in 73 patients (17.7%). However, when defined as HbA1c < 6.0% and GA < 16.0% without treatment, "burnt-out diabetes" was found in 45 patients (10.9%). CONCLUSIONS:Although the "burnt-out diabetes" phenomenon was present in 17.7% of patients with diabetes on PD based on HbA1c, the rate was significantly decreased to 10.9% when taking GA into account. 10.1016/j.diabres.2018.07.026
    New-onset glucose disorders in peritoneal dialysis patients: a meta-analysis and systematic review. Xue Cheng,Gu Yan-Yan,Cui Cheng-Ji,Zhou Chen-Chen,Wang Xian-Dong,Ruan Meng-Na,Huang Lin-Xi,Chen Si-Xiu,Yang Bo,Chen Xu-Jiao,Qian Yi-Xin,Wu Jun,Zhao Xue-Zhi,Zhang Yu-Qiang,Mei Chang-Lin,Zhang Shou-Lin,Xu Jing,Mao Zhi-Guo Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association BACKGROUND:Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism disturbance (GMD). The incidence and prevalence of new-onset GMD, including diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fast glucose (IFG), after initiation of PD, as well as their correlated influence factors, varies among studies in different areas and of different sample sizes. Also, the difference compared with hemodialysis (HD) remained unclear. Thus we designed this meta-analysis and systematic review to provide a full landscape of the occurrence of glucose disorders in PD patients. METHODS:We searched the MEDLINE, Embase, Web of Science and Cochrane Library databases for relevant studies through September 2018. Meta-analysis was performed on outcomes using random effects models with subgroup analysis and sensitivity analysis. RESULTS:We identified 1124 records and included 9 studies involving 13 879 PD patients. The pooled incidence of new-onset DM (NODM) was 8% [95% confidence interval (CI) 4-12; I2 = 98%] adjusted by sample sizes in PD patients. Pooled incidence rates of new-onset IGT and IFG were 15% (95% CI 3-31; I2 = 97%) and 32% (95% CI 27-37), respectively. There was no significant difference in NODM risk between PD and HD [risk ratio 0.99 (95% CI 0.69-1.40); P = 0.94; I2 = 92%]. PD patients with NODM were associated with an increased risk of mortality [hazard ratio 1.06 (95% CI 1.01-1.44); P < 0.001; I2 = 92.5%] compared with non-DM PD patients. CONCLUSIONS:Around half of PD patients may develop a glucose disorder, which can affect the prognosis by significantly increasing mortality. The incidence did not differ among different ethnicities or between PD and HD. The risk factor analysis did not draw a definitive conclusion. The glucose tolerance test should be routinely performed in PD patients. 10.1093/ndt/gfz116
    Monocyte to high-density lipoprotein ratio and cardiovascular events in patients on peritoneal dialysis. Zhan Xiaojiang,Pan Dan,Wei Xin,Wen Dan,Yan Caixia,Xiao Jun Nutrition, metabolism, and cardiovascular diseases : NMCD BACKGROUND AND AIMS:The monocyte to high-density lipoprotein cholesterol ratio (MHR) is associated with multiple cardiovascular diseases. However, the role of the MHR in predicting cardiovascular diseases in patients on peritoneal dialysis remains unclear. METHODS AND RESULTS:Eight hundred and eighty incident peritoneal dialysis patients were enrolled from November 1, 2005, to February 28, 2017, and followed until May 31, 2017. Primary outcomes were cardiovascular events. Using the X-tile program, these patients were divided into three groups according to the MHR. Kaplan-Meier method and Cox regressions were used for survival analysis. During a median follow-up period of 26 months (interquartile range: 12-39 months), 139 cardiovascular events were recorded. After multiple adjustment, the high MHR group was associated with a 1.97-fold increase in the cardiovascular events hazard compared to that of the low group in the overall population (hazard ratio: 1.97; 95% CI, 1.19-3.28; P = 0.009). Subgroup analysis demonstrated that the association between the MHR and a higher risk of cardiovascular events was strongest in the subgroup of patients with diabetes (P for interaction = 0.004). In this subgroup, the high MHR group was found to be associated with a higher risk of cardiovascular events compared to the low group (hazard ratio: 7.69; 95% CI, 2.76-21.47). CONCLUSION:This study suggests that the MHR is independently associated with the risk of cardiovascular events in patients undergoing peritoneal dialysis, and diabetes status can influence the association between the MHR and the risk of cardiovascular events. 10.1016/j.numecd.2020.03.011
    Comparison of clinical features and outcomes in peritoneal dialysis-associated peritonitis patients with and without diabetes: A multicenter retrospective cohort study. Meng Ling-Fei,Yang Li-Ming,Zhu Xue-Yan,Zhang Xiao-Xuan,Li Xin-Yang,Zhao Jing,Liu Shi-Chen,Zhuang Xiao-Hua,Luo Ping,Cui Wen-Peng World journal of diabetes BACKGROUND:The number of end-stage renal disease patients with diabetes mellitus (DM) who are undergoing peritoneal dialysis is increasing. Peritoneal dialysis-associated peritonitis (PDAP) is a serious complication of peritoneal dialysis leading to technical failure and increased mortality in patients undergoing peritoneal dialysis. The profile of clinical symptoms, distribution of pathogenic organisms, and response of PDAP to medical management in the subset of end-stage renal disease patients with DM have not been reported previously. Discrepant results have been found in long-term prognostic outcomes of PDAP in patients with DM. We inferred that DM is associated with bad outcomes in PDAP patients. AIM:To compare the clinical features and outcomes of PDAP between patients with DM and those without. METHODS:In this multicenter retrospective cohort study, we enrolled patients who had at least one episode of PDAP during the study period. The patients were followed for a median of 31.1 mo. They were divided into a DM group and a non-DM group. Clinical features, therapeutic outcomes, and long-term prognostic outcomes were compared between the two groups. Risk factors associated with therapeutic outcomes of PDAP were analyzed using multivariable logistic regression. A Cox proportional hazards model was constructed to examine the influence of DM on patient survival and incidence of technical failure. RESULTS:Overall, 373 episodes occurred in the DM group ( = 214) and 692 episodes occurred in the non-DM group ( = 395). The rates of abdominal pain and fever were similar in the two groups ( > 0.05). The DM group had more infections with coagulase-negative Staphylococcus and less infections with () as compared to the non-DM group ( < 0.05). Multivariate logistic regression analysis revealed no association between the presence of diabetes and rates of complete cure, catheter removal, PDAP-related death, or relapse of PDAP ( > 0.05). Patients in the DM group were older and had a higher burden of cardiovascular disease, with lower level of serum albumin, but a higher estimated glomerular filtration rate ( < 0.05). Cox proportional hazards model confirmed that the presence of diabetes was a significant predictor of all-cause mortality (hazard ratio = 1.531, 95% confidence interval: 1.091-2.148, < 0.05), but did not predict the occurrence of technical failure ( > 0.05). CONCLUSION:PDAP patients with diabetes have similar symptomology and are predisposed to coagulase-negative Staphylococcus but not infection compared those without. Diabetes is associated with higher all-cause mortality but not therapeutic outcomes of PDAP. 10.4239/wjd.v11.i10.435
    Age, diabetes mellitus, and dialysis modality are associated with risk of poor muscle strength and physical function in hemodialysis and peritoneal dialysis patients. Silva Maryanne Zilli Canedo,Antonio Karina Jesus,Reis João Marcos Soares,Alves Leticia Salmazzo,Caramori Jacqueline Costa Teixeira,Vogt Barbara Perez Kidney research and clinical practice BACKGROUND:Due to the poor outcomes associated with the impairment of physical function and muscle strength in patients on maintenance dialysis, it is important to understand the factors that may influence physical function and muscle strength. The aim of this study was to explore the factors associated with physical function in hemodialysis and peritoneal dialysis patients. METHODS:Patients with chronic kidney disease on dialysis for at least 3 months, aged 18 years old or above, were enrolled. Physical function was assessed by handgrip strength, gait and sit-to-stand tests, and the Short Physical Performance Battery (SPPB). Clinical and laboratory data were collected to verify the association with physical function parameters through binary logistic regression. RESULTS:One-hundred ninety patients on maintenance dialysis were included; 140 patients (73.7%) on hemodialysis and 50 (26.3%) on peritoneal dialysis. The mean age was 57.3 ± 14.9 years, 109 (57.4%) were male, and 87 (45.8%) were older than 60 years. The median SPPB was 8.0 points (6.0-10.0 points) and the mean ± standard deviation of handgrip strength was 24.7 ± 12.2 kg. Binary logistic regression showed that age, type of renal replacement therapy, diabetes mellitus, and serum creatinine were significantly associated with both higher 4-meter gait test times and lower SPPB scores. Only age and diabetes mellitus were associated with higher sit-to-stand test times, while age and ferritin were associated with lower handgrip strength. CONCLUSION:Age, diabetes mellitus, serum creatinine, and hemodialysis modality are factors related to physical function in dialysis patients. 10.23876/j.krcp.20.159
    Superiority of glycated albumin over glycated haemoglobin as indicator of glycaemic control and predictor of all-cause mortality in patients with type 2 diabetes mellitus receiving peritoneal dialysis. Miyabe Mizuki,Kurajoh Masafumi,Mori Katsuhito,Okuno Senji,Okada Shigeki,Emoto Masanori,Tsujimoto Yoshihiro,Inaba Masaaki Annals of clinical biochemistry 10.1177/0004563219873688
    New-Onset Diabetes Mellitus in Peritoneal Dialysis and Hemodialysis Patients: Frequency, Risk Factors, and Prognosis-A Review. Yarragudi Rajashri,Gessl Alois,Vychytil Andreas Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy New-onset diabetes mellitus (NODM) is observed in both hemodialysis (HD) and peritoneal dialysis (PD) patients. The prevalence of NODM in dialysis patients is slightly higher compared to subjects of the general population. Based on currently published data there is no convincing evidence that the risk of NODM is different between HD and PD patients. Data on the effect of glucose load on risk of NODM in dialysis patients remain controversial. PD modality (automated or continuous ambulatory PD) has no significant influence on NODM incidence. Chronic inflammation is associated with NODM in dialysis patients. Reported differences in NODM between PD and HD patients are possibly also influenced by differences in demographic factors between these patient groups. Mortality in NODM patients is lower than mortality in patients with preexisting DM. This may be partly explained by the younger age and lower number of comorbidities in patients with NODM. 10.1111/1744-9987.12800
    The Effect of Far-Infrared Therapy on the Peritoneal Expression of Glucose Degradation Products in Diabetic Patients on Peritoneal Dialysis. Chang Chia-Ning,Niu Chih-Yuan,Tan Ann Charis,Chan Chia-Hao,Chen Chun-Fan,Chen Tz-Heng,Li Szu-Yuan,Chen Yung-Tai,Chen Fan-Yu,Liu Wen-Sheng,Lin Chih-Ching,Wei Guor-Jien International journal of molecular sciences Peritoneal dialysis (PD) is a treatment modality for end-stage renal disease (ESRD) patients. Dextrose is a common osmotic agent used in PD solutions and its absorption may exacerbate diabetes mellitus, a common complication of ESRD. PD solutions also contain glucose degradation products (GDPs) that may lead to encapsulating peritoneal sclerosis (EPS), a severe complication of PD. A previous study showed that far-infrared (FIR) therapy improved a patient's gastrointestinal symptoms due to EPS. Due to limited literature on the matter, this study aims to investigate dialysate GDPs and peritoneal function in diabetic patients on PD. Thirty-one PD patients were enrolled and underwent 40 min of FIR therapy twice daily for six months. We demonstrated the effect of FIR therapy on the following: (1) decrease of methylglyoxal = 0.02), furfural ( = 0.005), and 5-hydroxymethylfurfural ( = 0.03), (2) increase of D/D0 glucose ratio ( = 0.03), and (3) decrease of potassium levels ( = 0.008) in both DM and non-DM patients, as well as (4) maintenance and increase of peritoneal Kt/V in DM and non-DM patients, respectively ( = 0.03). FIR therapy is a non-invasive intervention that can decrease dialysate GDPs in PD patients by improving peritoneal transport rate and solute removal clearance, while also maintaining dialysis adequacy. 10.3390/ijms22073732
    Sodium toxicity in peritoneal dialysis: mechanisms and "solutions". Borrelli Silvio,De Nicola Luca,Minutolo Roberto,Perna Alessandra,Provenzano Michele,Argentino Gennaro,Cabiddu Gianfranca,Russo Roberto,La Milia Vincenzo,De Stefano Toni,Conte Giuseppe,Garofalo Carlo, Journal of nephrology The major trials in peritoneal dialysis (PD) have demonstrated that increasing peritoneal clearance of small solutes is not associated with any advantage on survival, whereas sodium and fluid overload heralds higher risk of death and technique failure. On the other hand, higher sodium and fluid overload due to loss of residual kidney function (RKF) and higher transport membrane is associated with poor patient and technique survival. Recent experimental studies also show that, independently from fluid overload, sodium accumulation in the peritoneal interstitium exerts direct inflammatory and angiogenetic stimuli, with consequent structural and functional changes of peritoneum, while in patients with Chronic Kidney Disease sodium stored in interstitial skin acts as independent determinant of left ventricular hypertrophy. Noteworthy, this tissue pool of sodium is modifiable being removed by dialysis. Therefore, novel PD strategies to optimize sodium removal, including the use of bimodal and/or low-sodium solutions, are actively tested. Nonetheless, a holistic approach aimed at preserving peritoneal function and the kidney may represent the key of therapy success in the hard task of preserving adequate sodium balance in PD patients. In this review, we describe the available evidence on sodium toxicity in PD, either related or unrelated to fluid overload, and we also discuss about possible "solutions" to preserve or restore sodium balance in PD patients. 10.1007/s40620-019-00673-4
    Comparison of sodium removal in peritoneal dialysis patients treated by continuous ambulatory and automated peritoneal dialysis. Maharjan Sarju Raj Singh,Davenport Andrew Journal of nephrology BACKGROUND:Optimal fluid balance for peritoneal dialysis (PD) patients requires both water and sodium removal. Previous studies have variously reported that continuous ambulatory peritoneal dialysis (CAPD) removes more or equivalent amounts of sodium than automated PD (APD) cyclers. We therefore wished to determine peritoneal dialysate losses with different PD treatments. METHODS:Peritoneal and urinary sodium losses were measured in 24-h collections of urine and PD effluent in patients attending for their first assessment of peritoneal membrane function. We adjusted fluid and sodium losses for CAPD patients for the flush before fill technique. RESULTS:We reviewed the results from 659 patients, mean age 57 ± 16 years, 56.3% male, 38.9% diabetic, 24.0% treated by CAPD, 22.5% by APD and 53.5% APD with a day-time exchange, with icodextrin prescribed to 72.8% and 22.7 g/L glucose to 31.7%. Ultrafiltration was greatest for CAPD 650 (300-1100) vs 337 (103-598) APD p < 0.001, vs 474 (171-830) mL/day for APD with a day exchange. CAPD removed most sodium 79 (33-132) vs 23 (- 2 to 51) APD p < 0.001, and 51 (9-91) for APD with a day exchange, and after adjustment for the CAPD flush before fill 57 (20-113), p < 0.001 vs APD. APD patients with a day exchanged used more hypertonic glucose dialysates [0 (0-5) vs CAPD 0 (0-1) L], p < 0.001. CONCLUSION:CAPD provides greater ultrafiltration and sodium removal than APD cyclers, even after adjusting for the flush-before fill, despite greater hypertonic usage by APD cyclers. Ultrafiltration volume and sodium removal were similar between CAPD and APD with a day fill. 10.1007/s40620-019-00646-7
    Orosomucoid can predict baseline peritoneal transport characteristics in peritoneal dialysis patients and reduce peritoneal proteins loss. Bao Manchen,Sun Zhaoxing,Yang Xiaoxiao,Ji Jun,Zhang Lin,Xiang Bo,Yan Guoquan,Ding Xiaoqiang,Zou Jianzhou,Yu Xiaofang Journal of proteomics Peritoneal dialysis (PD) is a replacement therapy for end-stage renal disease patients. In the first 4-8 weeks of PD, the patients were given an empirical dialysis prescription due to unknown peritoneal transport characteristics. Proteomic analysis could be used to identify serum biomarkers. In a discovery set, patients were divided into three groups according to the peritoneal equilibration test (PET) results: high (H), high average (HA), low average and low (LA&L) groups. A total of 1051 identified proteins were screened by Nano HPLC-MS/MS. The top two proteins among different peritoneal transport characteristics were Orosomucoid 2 (ORM2) and C-reactive protein (CRP). In a validation set, CRP was significantly elevated in H group than LA&L group, consistent with proteomic analysis. Serum ORM2 was enhanced in LA&L group compared with H and HA group. The expression of ORM2 in peritoneum was also enriched in LA&L group. At last, supplying exogenous ORM could reduce peritoneal proteins loss, without causing a pro-inflammatory response in mice. ORM2 and CRP could be used as biomarkers to predict the baseline peritoneal transport characteristics, and guide the early PD treatment. ORM may serve as a novel therapeutic target for decreasing peritoneal proteins loss in PD patients. SIGNIFICANCE: Peritoneal dialysis (PD) is associated with the functional alterations of the peritoneum. PD patients were often given an empirical dialysis prescription due to the unknown peritoneal transport characteristics in the first 4-8 weeks since PD started. Therefore, it is urgently needed to find biomarkers to predict the baseline peritoneal transport characteristics. In this study, we employed a proteomic analysis to identify serum biomarkers in a training set and verified the screened biomarkers in a validation set. We also found that Orosomucoid (ORM) has the potential to decrease peritoneal proteins loss in PD therapy. 10.1016/j.jprot.2021.104260
    Effects of two different dialytic treatments on inflammatory markers in people with end-stage renal disease with and without type 2 diabetes mellitus. Derosa Giuseppe,Libetta Carmelo,Esposito Pasquale,Borettaz Ilaria,Tinelli Carmine,D'angelo Angela,Maffioli Pamela Cytokine This study was aimed to evaluate the effects on some inflammatory markers of two dialytic treatments [bicarbonate dialysis (BHD) and hemodiafiltration (HDF)] in patients with severe chronic kidney disease. We evaluated: blood glucose, homeostasis model assessment insulin resistance index, homocistein (Hcs), high sensitivity C-reactive protein (hs-CRP), fibrinogen, lipoprotein (a) [Lp(a)], metalloproteinases-2, and -9 (MMP-2 and MMP-9), and soluble receptor for advanced glycation end products (sRAGE). Considering the all sample, we observed a decrease of sRAGE with BHD, but not with HDF. Fibrinogen, MMP-2, and -9, Hs-CRP decreased after HDF, but not after BHD. In diabetics, blood glucose decreased after HDF dialysis, but not after BHD. Soluble receptor for advanced glycation end products obtained with HDF were higher compared to BHD. Fibrinogen, MMP-2, MMP-9, Hcs, Hs-CRP decreased, and ADN increased after HDF, these changes did not happen after BHD. Furthermore, sRAGE, and ADN were higher, and MMP-2 lower after HDF. In euglycemic patients, instead, MMP-2, MMP-9, and Hs-CRP decreased, and ADN increased with HDF, but not with BHD. We can conclude that hemodiafiltration seems to greater reduce inflammatory markers, and it could be more suitable for people with type 2 diabetes. Registration number: ClinicalTrials.gov NCT01049152. 10.1016/j.cyto.2016.12.026
    Pulse pressure is not an independent predictor of outcome in type 2 diabetes patients with chronic kidney disease and anemia--the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT). Theilade S,Claggett B,Hansen T W,Skali H,Lewis E F,Solomon S D,Parving H-H,Pfeffer M,McMurray J J,Rossing P, Journal of human hypertension Pulse pressure (PP) remains an elusive cardiovascular risk factor with inconsistent findings. We clarified the prognostic value in patients with type 2 diabetes, chronic kidney disease (CKD) and anemia in the Trial to Reduce cardiovascular Events with Aranesp (darbepoetin alfa) Therapy. In 4038 type 2 diabetes patients, darbepoetin alfa treatment did not affect the primary outcome. Risk related to PP at randomization was evaluated in a multivariable model including age, gender, kidney function, cardiovascular disease (CVD) and other conventional risk factors. End points were myocardial infarction (MI), stroke, end stage renal disease (ESRD) and the composite of cardiovascular death, MI or hospitalization for myocardial ischemia, heart failure or stroke (CVD composite). Median (interquartile range) age, gender, eGFR and PP was 68 (60-75) years, 57.3% women, 33 (27-42) ml min(-1) per 1.73 m2 and 60 (50-74) mm Hg. During 29.1 months (median) follow-up, the number of events for composite CVD, MI, stroke and ESRD was 1010, 253, 154 and 668. In unadjusted analyses, higher quartiles of PP were associated with higher rates per 100 years of follow-up of all end points (P⩽0.04), except stroke (P=0.52). Adjusted hazard ratios (95% confidence interval) per one quartile increase in PP were 1.06 (0.99-1.26) for MI, 0.96 (0.83-1.11) for stroke, 1.01 (0.94-1.09) for ESRD and 1.01 (0.96-1.07) for CVD composite. Results were similar in continuous analyses of PP (per 10 mm Hg). In patients with type 2 diabetes, CKD and anemia, PP did not independently predict cardiovascular events or ESRD. This may reflect confounding by aggressive antihypertensive treatment, or PP may be too rough a risk marker in these high-risk patients. 10.1038/jhh.2015.22
    Decreased plasma α-Klotho predict progression of nephropathy with type 2 diabetic patients. Kim Sang Soo,Song Sang Heon,Kim In Joo,Lee Eun Young,Lee Su Mi,Chung Choon Hee,Kwak Ihm Soo,Lee Eun Kyung,Kim Yong Ki Journal of diabetes and its complications AIM:The potential role of soluble α-klotho in diabetic kidney disease has not yet been evaluated. The aim of this study was to evaluate the association of plasma and/or urine α-klotho with the progression of type 2 diabetic nephropathy. METHODS:The baseline values of plasma and urine α-klotho were measured in 147 patients with type 2 diabetes mellitus with an estimated glomerular filtration rate (eGFR) of ≥60mL/min/1.73m(2). In this prospective observational study, a total of 109 type 2 diabetic patients were followed up for 34months (8-50 months). RESULTS:Plasma α-klotho, but not urine α-klotho, was negatively correlated with the decline of eGFR (r=-0.304, P=0.001; r=0.042, P=0.068, respectively). After adjusting for several clinical parameters, baseline eGFR and urine ACR, plasma α-klotho was significantly associated with the decline of eGFR (r=-0.219, P=0.008). In the normoalbuminuria group (n=63), the plasma α-klotho remained significantly associated with a decline in eGFR (r=0.324, P=0.004) in the final model. CONCLUSIONS:It is suggested that plasma α-klotho may be an early biomarker for predicting renal impairment in type 2 diabetic patients. The disappearance of a compensatory increase of plasma α-klotho might be a predictive marker for the progression of type 2 diabetic nephropathy. 10.1016/j.jdiacomp.2016.03.006
    Effect of Sofosbuvir-Based Hepatitis C Virus Therapy on Kidney Function in Patients with CKD. Sise Meghan E,Backman Elke,Ortiz Guillermo A,Hundemer Gregory L,Ufere Nneka N,Chute Donald F,Brancale Joseph,Xu Dihua,Wisocky Jessica,Lin Ming V,Kim Arthur Y,Thadhani Ravi,Chung Raymond T Clinical journal of the American Society of Nephrology : CJASN BACKGROUND AND OBJECTIVES:Hepatitis C virus infection is common in patients with CKD and leads to accelerated progression to ESRD. Sofosbuvir is a potent direct-acting antiviral therapy against hepatitis C virus; however, there are concerns about its safety in patients with CKD. The objective of our study was to determine the safety and efficacy of sofosbuvir in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We studied a retrospective observational cohort of patients with CKD defined by eGFR<60 ml/min per 1.73 m, ≥30 mg albuminuria per 1 g creatinine, or ≥200 mg proteinuria per 1 g creatinine who received sofosbuvir-based therapy in a large health care system. Regression models were constructed to predict likelihood of sustained virologic response, detect adverse events, and examine changes in eGFR from baseline to follow-up. RESULTS:Ninety-eight patients with CKD (42% stage 1 or 2 CKD and 58% stage 3 CKD) were included. Mean age was 62 years old, 78% were men, and 65% were white. Additionally, 49% of patients had diabetes, 38% of patients had cirrhosis, and 33% of patients had prior solid organ transplant. Overall sustained virologic response was 81% and varied by regimen used and viral genotype. Average baseline eGFR was equivalent to average on-treatment eGFR, but seven patients experienced a rise in creatinine ≥1.5 times baseline while taking sofosbuvir; all but one recovered. In patients with eGFR<60 ml/min per 1.73 m at baseline (stage 3 CKD), regression models showed that hepatitis C cure was associated with a 9.3 (95% confidence interval, 0.44 to 18) ml/min per 1.73 m improvement in eGFR during the 6-month post-treatment follow-up period. Adverse events were common (81%), but serious adverse events (17%) and treatment discontinuations (8%) were uncommon. CONCLUSIONS:Sofosbuvir-based direct-acting antiviral therapy is safe and effective in a cohort of patients with CKD infected with hepatitis C. 10.2215/CJN.02510317
    The association between serum uric acid to creatinine ratio and renal disease progression in type 2 diabetic patients in Chinese communities. Chunlei Yao,Liubao Gu,Tao Wang,Changying Xing Journal of diabetes and its complications AIMS:Serum uric acid (UA) increases in patients with kidney disease due to the impaired UA clearance. The present study sought to evaluate the association between UA/creatinine ratio (UA/Cr) and renal disease progression in patients with type 2 diabetes mellitus (T2DM) in Chinese communities. METHODS:In the present retrospective longitudinal study, 3432 Chinese T2DM patients recruited from 11 community healthcare centers in Nanjing, China were included. Renal disease progression was defined as the occurrence of estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m or doubling of baseline serum creatinine level. Cox regression analysis was used to estimate the association between UA/Cr and renal disease progression. RESULTS:During a median follow-up of 30 months, 58 (1.70%) patients experienced progression of renal disease, which was more common among those with older ages, longer diabetes duration, and higher baseline eGFR. Multivariate analysis revealed that UA/Cr was an independent risk factor for renal disease progress (hazard ratio 1.364 [95% CI 1.131-1.646], P = 0.001) independently of age, sex, and other potential confounders. CONCLUSIONS:UA/Cr might be a novel predictor of chronic kidney disease progression in T2DM patients. 10.1016/j.jdiacomp.2018.10.013
    Associated factors related to chronic kidney disease progression in elderly patients. Tótoli Cláudia,Carvalho Aluizio Barbosa,Ammirati Adriano Luiz,Draibe Sergio Antônio,Canziani Maria Eugênia F PloS one BACKGROUND:Chronic Kidney Disease (CKD) is a worldwide public health problem. The prevalence of CKD is rising especially in elderly, as consequence of population-ageing related to socioeconomic development and better life expectancy. There are scarce studies evaluating CKD progression and its associated factors in elderly patients. METHODS:This is a retrospective observational study including 340 patients (≥ 65 years old) CKD stages 3a-5 non-dialysis, incidents in an outpatient CKD clinic, followed by 2.1 years. CKD progression was assessed by the slope of eGFR calculated by CKD-EPI and BIS 1 equations. The patients were divided in progressor and non-progressor groups (eGFR slope < or ≥ 0 mL/min/1.73 m2/year, respectively). RESULTS:Kidney function declined in 193 (57%) patients. In this group, the progression rate was -2.83 (-5.1 / -1.1) mL /min /1.73 m2 /year. Compared to non progressor, the progressor patients were younger [72 (69-78) vs. 76 (69-80) years; p = 0.02]; had higher proportion of diabetic nephropathy, higher serum phosphorus [3.8 (3.3-4.1) vs. 3.5 (3.9-4.1) mg/dL; p = 0.04] and proteinuria [0.10 (0-0.9 vs. 0 (0-0.3)] g/L; p = 0.007)] at the admission. In the logistic regression analysis adjusted for gender and eGFR, proteinuria was independently associated with CKD progression [OR (Odds Ratio) (1.83; 95% CI, 1.17-2.86; p < 0.01)]. CONCLUSION:CKD progression was observed in the majority of elderly CKD patients and proteinuria was the most important factor associated to the decline of kidney function in this population. 10.1371/journal.pone.0219956
    Plasma uric acid and renal haemodynamics in type 2 diabetes patients. Suijk Danii Ls,Smits Mark M,Muskiet Marcel Ha,Tonneijck Lennart,Kramer Mark Hh,Joles Jaap A,van Raalte Daniël H Nephrology (Carlton, Vic.) AIM:Increased plasma uric acid (PUA) concentrations are associated with chronic kidney disease in type 2 diabetes (T2D) patients. The mechanisms involved remain unclear. We investigated the relation between PUA and (intra)renal haemodynamics in T2D patients without overt kidney disease. METHODS:Eighty-eight white men and women with T2D were included (age 64 (58-68) years; body mass index 30.9 (28.3-33.6) kg/m ; glycated haemoglobin 7.1 (6.8-7.6)%). Plasma UA and fractional excretion of UA were measured, while glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were assessed by inulin and PAH-clearance techniques, respectively. Effective renal vascular resistance was calculated (ERVR). Renal afferent and efferent arteriolar resistances and glomerular hydrostatic pressure were estimated. Relationships between PUA and fractional excretion of UA and (intra)renal haemodynamic parameters were evaluated by multivariable linear regression analyses. RESULTS:Plasma UA concentrations were at the higher end of the normal range in most participants: 342 ± 68 μmol/L or 5.7 ± 1.1 mg/dL (mean ± SD). In multivariable analyses, PUA concentrations were negatively associated with GFR (r = -0.471; P = 0.001), ERPF (r = -0.436; P = 0.003) and glomerular hydrostatic pressure (r = -0.427; P = 0.003). In contrast, PUA concentrations had a positive correlation with ERVR (r = 0.474; P = 0.001), but not with efferent vascular resistance. Fractional excretion of UA was not related to renal haemodynamics. CONCLUSION:Plasma UA was negatively associated to GFR, ERPF but positively related to ERVR in T2D patients without overt renal impairment. Plasma UA-related increase in ERVR may be related to increased arterial afferent tone, which may put the kidney at risk for renal damage through ischaemia. 10.1111/nep.13645
    Prognostic significance of NGAL in early stage chronic kidney disease. Basturk Taner,Sari Ozlem,Koc Yener,Eren Nezaket,Isleem Mahmoud,Kara Ekrem,Sevinc Mustafa,Sakaci Tamer,Ahbap Elbis,Hasbal Nuri B,Bayrakdar Caglayan Feyza,Unsal Abdulkadir Minerva urologica e nefrologica = The Italian journal of urology and nephrology BACKGROUND:Neutrophilgelatinase-associated lipocalin (NGAL) has been proven to be a useful biomarker for early detection of acute kidney injury, but it is not known whether adding NGAL measurements to conventional risk factors will improve the risk assessment in the setting of chronic kidney disease (CKD). The aim of the present study was to examine the correlation of NGAL with early stage renal impairment in CKD and to evaluate its prognostic value in these subjects. METHODS:This is a prospective observational cohort study of 54 patients with early stage (stage 1-2) CKD. Patients aged between 18 and 65 years with stable disease were enrolled in this study. Patients with a history of primary glomerulonephritis, diabetes mellitus, acute kidney injury, systemic diseases and stage 3-4-5 CKD were excluded from the study group. Estimated glomerular filtration (eGFR) rate was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. The patients were followed for two years to determine the ability of baseline NGAL for prediction of renal outcome. In our study disease progression was defined as changes in eGFR (ΔeGFR) and proteinuria (Δproteinuria). Patients divided into two groups according to NGAL cut-off value as group 1 (N.=23, NGAL ≤98.71 ng/mL) and group 2 (N.=31, NGAL >98.71 ng/mL). RESULTS:Out of 54 patients (mean age: 45.6±7.6 years, 64.8% female, baseline eGFR: 84.6±16.8 mL/min/1.73 m2, baseline NGAL level: 157.47±121.52 ng/mL); 18 patients were stage 1 and 36 patients were stage 2 CKD. In the ROC analysis, we found that the optimal cut-off value of NGAL for predicting stage 2 CKD was 98.71ng/mL (P=0.005) with the 72.2% sensitivity and 72.2% specificity. In correlation analysis, we evaluated significantly positive correlations between NGAL and CKD stage (r=0.389, P=0.004), baseline/last serum creatinine level (r=0.530, P<0.001 and r=0.439, P=0.003; respectively), last proteinuria level (r=0.359, P=0.043). There were significantly negative correlation between NGAL and baseline/last eGFR (r=-0.498, P<0.001 and r=-0.462, P=0.002; respectively). Compared to the group 1, we determined that group 2 patients had further deterioration in renal functions regarding ΔeGFR (-1.12±12.6 mL/min vs. -1.46±12.4 mL/min: respectively, P=0.930) and Δproteinuria (98.1±569.3 mg/day vs. 339±701.6 mg/day; respectively, P=0.305); however these differences were not statistically significant at the end of the two years follow-up period. CONCLUSIONS:Altough NGAL has a positive correlation with disease severity, it does not seem to be a marker of disease progression in patients with early stage CKD. But further studies stated in different patient groups may also explain the usability of NGAL in clinical practice. 10.23736/S0393-2249.16.02770-3
    High serum adiponectin is associated with anemia development in chronic kidney disease: The results from the KNOW-CKD study. Kim Hyoungnae,Yun Hae-Ryong,Park Seohyun,Jhee Jong Hyun,Park Jung Tak,Yoo Tae-Hyun,Lee Kyu-Beck,Kim Yeong-Hoon,Sung Su-Ah,Lee Joongyub,Kang Shin-Wook,Choi Kyu Hun,Ahn Curie,Han Seung Hyeok Cytokine BACKGROUND:Adiponectin is an adipokine secreted by adipocytes. A low adiponectin level is a significant risk factor of diabetes mellitus and cardiovascular disease. Recent studies have shown that adiponectin is negatively associated with hematopoiesis and predicts the development of anemia in the general population. In chronic kidney disease (CKD) patients, circulating adiponectin level is paradoxically elevated and the role of adiponectin is complex. Therefore, we evaluated the relationship between adiponectin and anemia in these patients. METHODS:This prospective longitudinal study included 2113 patients from the KNOW-CKD study (KoreaN cohort study for Outcome in patients With CKD), after excluding 125 without data on adiponectin levels. Hemoglobin levels were measured yearly during a mean follow-up period of 23.7 months. Anemia was defined as hemoglobin levels of <13.0 and 12.0 g/dL for men and women, respectively. RESULTS:Mean patient age was 53.6 ± 12.2 years, and 1289 (61%) were men. The mean estimated glomerular filtration rate (eGFR) was 50.4 ± 30.2 mL min 1.73 m. Serum adiponectin level was inversely associated with body mass index, eGFR, log-transformed C-reactive protein, and positively with Charlson comorbidity index, urine protein to creatinine ratio, and high density lipoprotein cholesterol. In addition, serum adiponectin level was also negatively correlated with hemoglobin level and reticulocyte production index in both men and women. In multivariable linear regression analysis after adjustment of multiple confounders, adiponectin was negatively associated with hemoglobin (men, β = -0.219, P < .001; women, β = -0.09, P = .025). Among 1227 patients without anemia at baseline, 307 newly developed anemia during the follow-up period. In multivariable Cox regression analysis after adjustment of confounders, high adiponectin level was significantly associated with an increased risk of incident anemia (per 1 µg/mL increase, hazard ratio, 1.02; 95% confidence interval 1.01-1.04; P = .001). CONCLUSIONS:A high serum adiponectin level is independently associated with a low hemoglobin level and predicts the development of anemia in patients with CKD. These findings reveal the potential role of adiponectin in CKD-related anemia. 10.1016/j.cyto.2017.12.018
    Contrast-Induced Nephropathy in STEMI Patients With and Without Chronic Kidney Disease. Jain Tarun,Shah Sunay,Shah Jainil,Jacobsen Gordon,Khandelwal Akshay Critical pathways in cardiology INTRODUCTION:Contrast-induced nephropathy (CIN) following percutaneous coronary intervention (PCI) is associated with adverse outcomes; however, there are scarce data comparing clinical outcomes of post-PCI CIN in ST elevation myocardial infarction (STEMI) patients with and without chronic kidney disease (CKD). We sought to assess the incidence, clinical predictors, and short-term and long-term clinical outcomes of post-PCI CIN in STEMI patients with and without CKD. METHODS:We performed a retrospective observational cohort study involving 554 patients who underwent PCI for STEMI from February 2010 to November 2013. CKD was defined as estimated glomerular filtration rate ≤60 mL/min and CIN as creatinine increase by ≥25% or ≥0.5 mg/dL from baseline within 72 hours after catheterization contrast exposure. RESULTS:In the entire population, CIN developed in 89 (16%) patients. The incidence of CIN was 19.7% (27/137) in CKD patients and 11.1% (62/417) in non-CKD patients, P < 0.05. Univariate analysis predictors of CIN were older age (65 vs. 60 years), diabetes (35% vs. 21%), peripheral artery disease (11% vs. 5%), cardiogenic shock (24% vs. 13%), hemodynamic support placement (34% vs. 14%), and Mehran score (9.4 ± 7 vs. 5.4 ± 5.2) with all P < 0.05. The predictors of CIN were the same across the CKD and non-CKD cohort with the exception of diabetes. In multivariate analysis, the strongest predictor of CIN in CKD patients was diabetes (odds ratio, 5.8; CI, 1.8-18.6); however, diabetes was not a predictor in the non-CKD population. In the non-CKD population, each single unit increase in the Mehran score was associated with a 1.1 times greater likelihood of CIN (odds ratio, 1.1; CI, 1.01-1.2). Patients with CIN had higher rates of inpatient mortality (14.6% vs. 2.8%), longer length of hospitalization (8 ± 11 vs. 3.4 ± 4.4 days), need for inpatient dialysis (11.2% vs. 0%), higher 30-day mortality (14.6% vs. 3.0%), and higher incidence of long-term serum creatinine >0.5 mg/dL from baseline (16.9% vs. 2.4%) with all P < 0.05. CONCLUSIONS:Overall, we found that CKD patients undergoing PCI for STEMI have a higher incidence of CIN than non-CKD patients. CIN confers worse short-term and long-term outcomes irrespective of baseline renal function. 10.1097/HPC.0000000000000123
    Resistant Hypertension, Time-Updated Blood Pressure Values and Renal Outcome in Type 2 Diabetes Mellitus. Viazzi Francesca,Piscitelli Pamela,Ceriello Antonio,Fioretto Paola,Giorda Carlo,Guida Pietro,Russo Giuseppina,De Cosmo Salvatore,Pontremoli Roberto, Journal of the American Heart Association BACKGROUND:Apparent treatment resistant hypertension (aTRH) is highly prevalent in patients with type 2 diabetes mellitus (T2D) and entails worse cardiovascular prognosis. The impact of aTRH and long-term achievement of recommended blood pressure (BP) values on renal outcome remains largely unknown. We assessed the role of aTRH and BP on the development of chronic kidney disease in patients with T2D and hypertension in real-life clinical practice. METHODS AND RESULTS:Clinical records from a total of 29 923 patients with T2D and hypertension, with normal baseline estimated glomerular filtration rate and regular visits during a 4-year follow-up, were retrieved and analyzed. The association between time-updated BP control (ie, 75% of visits with BP <140/90 mm Hg) and the occurrence of estimated glomerular filtration rate <60 and/or a reduction ≥30% from baseline was assessed. At baseline, 17% of patients had aTRH. Over the 4-year follow-up, 19% developed low estimated glomerular filtration rate and 12% an estimated glomerular filtration rate reduction ≥30% from baseline. Patients with aTRH showed an increased risk of developing both renal outcomes (adjusted odds ratio, 1.31 and 1.43; <0.001 respectively), as compared with those with non-aTRH. No association was found between BP control and renal outcomes in non-aTRH, whereas in aTRH, BP control was associated with a 30% (=0.036) greater risk of developing the renal end points. CONCLUSIONS:ATRH entails a worse renal prognosis in T2D with hypertension. BP control is not associated with a more-favorable renal outcome in aTRH. The relationship between time-updated BP and renal function seems to be J-shaped, with optimal systolic BP values between 120 and 140 mm Hg. 10.1161/JAHA.117.006745
    Serum bilirubin level and its impact on the progression of chronic kidney disease. Uludag Koray,Oguzhan Nilufer,Arıkan Tamer,Boz Gulsah International urology and nephrology PURPOSE:To examine whether an elevated serum total bilirubin level affects the decline in renal function or new-onset chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (DM2). METHODS:This was a longitudinal observational study in patients who presented at the University of Health Sciences Hospital in Kayseri. Five hundred twenty-nine patients with DM2 who had conserved renal function were enrolled (estimated glomerular filtration rate > 60 ml/min/1.73 m). Arising CKD stage 3 was the outcome measure. The patients were separated into three groups based on the total serum bilirubin levels. The first group (G1) ranged from 0.1 to 0.3, the second (G2) 0.4-0.5, and the third (G3) 0.6-0.9 mg/dl. The effect of total serum bilirubin levels on CKD 3 development was assessed using Cox proportional hazards regression. RESULTS:The risk of the CKD stage 3 development was highest in G1 who has the lowest serum total bilirubin levels (G1 vs. G3; hazard ratio [HR], 2.02; 95% confidence interval [CI] 1.21-3.36; p = 0.007). In addition, G2 had a significant risk of CKD stage 3 development (G2 vs. G3; hazard ratio [HR], 1.58; 95% confidence interval [CI] 1.08-2.32; p = 0.018). In the adjusted analysis, compared to G2 and G3, G1 had the highest risk (G1 vs. G3; hazard ratio [HR], 2.20; 95% confidence interval [CI] 1.29-3.77; p = 0.004). Similarly, G2 had a higher risk compared to G3 (hazard ratio [HR], 1.57; 95% confidence interval [CI] 1.05-2.34; p = 0.028). CONCLUSIONS:Serum bilirubin may predict the progression of CKD in patients with type 2 diabetes and preserved kidney function. 10.1007/s11255-018-1923-9
    Low serum bilirubin level predicts the development of chronic kidney disease in patients with type 2 diabetes mellitus. Ahn Kang Hee,Kim Sang Soo,Kim Won Jin,Kim Jong Ho,Nam Yun Jeong,Park Su Bin,Jeon Yun Kyung,Kim Bo Hyun,Kim In Joo,Kim Yong Ki The Korean journal of internal medicine BACKGROUND/AIMS:We evaluated whether serum bilirubin levels can predict the development of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM). METHODS:This was a retrospective observational longitudinal study of patients presenting at the Pusan National University Hospital. A total of 349 patients with T2DM and preserved kidney function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m) were enrolled. The main outcome was the development of CKD stage 3 or greater. The patients were divided into four groups according to the quartiles of the total serum bilirubin levels at baseline. RESULTS:The group with the lowest range of total serum bilirubin level (Q1) showed the highest cumulative incidence of CKD stage 3 or greater than that of the other lower quartiles (Q1 vs. Q4; hazard ratio [HR], 6.75; 95% confidence interval [CI], 1.54 to 29.47; = 0.011). In multivariate analysis, the risk of developing CKD stage 3 or greater was higher in the second lowest quartile of the serum bilirubin level than that in the highest quartile of the serum bilirubin level (Q2 vs. Q4; HR, 9.36; 95% CI, 1.33 to 65.73; = 0.024). In the normoalbuminuria subgroup (n = 236), multivariate analysis showed that the risk of developing CKD stage 3 or greater was higher in the lowest quartile of the serum bilirubin level than that in the highest quartile of the serum bilirubin level (Q1 vs. Q4; HR, 7.36; 95% CI, 1.24 to 35.82; = 0.019). CONCLUSIONS:Serum bilirubin might be an early clinical marker for predicting the progression of CKD in patients with T2DM and preserved renal function. 10.3904/kjim.2015.153
    Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy. Kim Kyeong-Seok,Lee Jin-Sol,Park Jae-Hyeon,Lee Eun-Young,Moon Jong-Seok,Lee Sang-Kyu,Lee Jong-Sil,Kim Jung-Hwan,Kim Hyung-Sik Biomedicines Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy. 10.3390/biomedicines9050457
    Evidence of Early Diabetic Nephropathy in Pediatric Type 1 Diabetes. Mamilly Leena,Mastrandrea Lucy D,Mosquera Vasquez Claudia,Klamer Brett,Kallash Mahmoud,Aldughiem Ahmad Frontiers in endocrinology Background:Diabetic nephropathy (DN) is one of the most common microvascular complications in type 1 diabetes Mellitus (T1D). Urinary markers of renal damage or oxidative stress may signal early stages of DN. The association of these markers with blood pressure (BP) patterns and glycemic variability (GV) in children is yet to be explored. Methods:Subjects between the ages of 10 and 21 years with T1D were enrolled. Continuous glucose monitoring (CGM) and ambulatory blood pressure monitoring (ABPM) were performed on each subject. Urine samples were collected and analyzed for albumin, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) and pentosidine. Results:The study included 21 subjects (62% female) with median age of 16.8 (IQR: 14.5, 18.9). Median HbA1C was 8.4 (IQR: 7.5, 9.3). While microalbuminuria was negative in all but one case (4.8%), urinary NGAL/Cr and pentosidine/Cr ratios were significantly elevated (P<0.001) in diabetic patients despite having normal microalbuminuria, and they correlated significantly with level of microalbumin/Cr (r=0.56 [CI: 0.17, 0.8] and r=0.79 [CI: 0.54, 0.91], respectively). Using ABPM, none had hypertension, however, poor nocturnal systolic BP dipping was found in 48% of cases (95% CI: 28-68%). Urinary NGAL/Cr negatively correlated with nocturnal SBP dipping (r=-0.47, CI: -0.76, -0.03). Urine NGAL/Cr also showed a significant negative correlation with HbA1c measurements, mean blood glucose, and high blood glucose index (r=-0.51 [CI: -0.78, -0.09], r=-0.45 [CI: -0.74, -0.03], and r=-0.51 [CI: -0.77, -0.1], respectively). Median urinary NGAL/Cr and pentosidine/Cr ratios were higher in the high GV group but were not significantly different. Discussion:This pilot study explores the role of ABPM and urinary markers of tubular health and oxidative stress in early detection of diabetic nephropathy. GV may play a role in the process of this diabetic complication. 10.3389/fendo.2021.669954
    Oxidative Stress Markers in Chronic Kidney Disease with Emphasis on Diabetic Nephropathy. Vodošek Hojs Nina,Bevc Sebastjan,Ekart Robert,Hojs Radovan Antioxidants (Basel, Switzerland) Diabetes prevalence is increasing worldwide, especially through the increase of type 2 diabetes. Diabetic nephropathy occurs in up to 40% of diabetic patients and is the leading cause of end-stage renal disease. Various factors affect the development and progression of diabetic nephropathy. Hyperglycaemia increases free radical production, resulting in oxidative stress, which plays an important role in the pathogenesis of diabetic nephropathy. Free radicals have a short half-life and are difficult to measure. In contrast, oxidation products, including lipid peroxidation, protein oxidation, and nucleic acid oxidation, have longer lifetimes and are used to evaluate oxidative stress. In recent years, different oxidative stress biomarkers associated with diabetic nephropathy have been found. This review summarises current evidence of oxidative stress biomarkers in patients with diabetic nephropathy. Although some of them are promising, they cannot replace currently used clinical biomarkers (eGFR, proteinuria) in the development and progression of diabetic nephropathy. 10.3390/antiox9100925
    Multifunctional agents based on benzoxazolone as promising therapeutic drugs for diabetic nephropathy. Zhang Xin,Chen Huan,Lei Yanqi,Zhang Xiaonan,Xu Long,Liu Wenchao,Fan Zhenya,Ma Zequn,Yin Zhechang,Li Lingyun,Zhu Changjin,Ma Bing European journal of medicinal chemistry Diabetic nephropathy (DN) is resulted from activations of polyol pathway and oxidative stress by abnormal metabolism of glucose, and no specific medication is available. We designed a novel class of benzoxazolone derivatives, and a number of individuals were found to have significant antioxidant activity and inhibition of aldose reductase of the key enzyme in the polyol pathway. The outstanding compound (E)-2-(7-(4-hydroxy-3-methoxystyryl)-2-oxobenzo[d]oxazol-3(2H)-yl)acetic acid was identified to reduce urinary proteins in diabetic mice suggesting an alleviation in the diabetic nephropathy, and this was confirmed by kidney hematoxylin-eosin staining. Further investigations showed blood glucose normalization, declined in the polyol pathway and lipid peroxides, and raised glutathione and superoxide dismutase activity. Thus, we suggest a therapeutic function of the compound for DN which could be attributed to the combination of hypoglycemic, aldose reductase inhibition and antioxidant. 10.1016/j.ejmech.2021.113269
    Diabetic nephropathy: A twisted thread to unravel. Dagar Neha,Das Pamelika,Bisht Priya,Taraphdar Amit Kumar,Velayutham Ravichandiran,Arumugam Somasundaram Life sciences Diabetic nephropathy (DN), a persistent microvascular problem of diabetes mellitus is described as an elevated level of albumin excretion in urine and impaired renal activity. The morbidity and mortality of type-1 diabetics and type-2 diabetics due to end stage renal disease is also a result of the increased prevalence of DN. DN typically occurs as a consequence of an association among metabolic and hemodynamic variables, activating specific pathways leading to renal injury. According to current interventions, intensive glucose regulation decreases the threat of DN incidence and growth, and also suppressing the renin-angiotensin system (RAS) is a significant goal for hemodynamic and metabolism-related deformities in DN. However, the pathogenesis of DN is multifactorial so novel approaches other than glucose and blood pressure control are required for treatment. This review briefly summarizes the reported pathogenesis of DN, current interventions for its treatment, and possible novel interventions to unweave the thread of DN. 10.1016/j.lfs.2021.119635
    Association of Vitamin D Deficiency with Diabetic Nephropathy. Hong So-Hyeon,Kim Young Bin,Choi Hoon Sung,Jeong Tae-Dong,Kim Jin Taek,Sung Yeon Ah Endocrinology and metabolism (Seoul, Korea) BACKGROUND:Low 25-hydroxyvitamin D (25OHD) levels are associated with the incidence of type 2 diabetes mellitus (T2DM). However, the association between 25OHD and metabolic health status or diabetic complications is inconclusive. We evaluated this relationship between vitamin D status and metabolic parameters and complications of T2DM. METHODS:This study included 1,392 patients with T2DM who visited Eulji and Ewha Diabetes Center between January 2011 and August 2016. Anthropometric parameters and laboratory tests including glycated hemoglobin (HbA1c), lipid profile, liver and kidney function, and urinary albumin-to-creatinine ratio (UACR) were evaluated. Diabetic macro- and microvascular complications were determined through a medical record review. Serum 25OHD concentrations were measured by chemiluminescent immunoassay. RESULTS:The mean 25OHD level was 16.8±9.6 ng/mL. Vitamin D deficiency (&lt;20 ng/mL) and severe deficiency (&lt;10 ng/mL) were observed in 990 (71.1%) and 351 (25.2%) participants, respectively. 25OHD level was positively correlated with age and highdensity lipoprotein cholesterol (HDL-C) level and negatively correlated with HbA1c, triglyceride level, and UACR. HDL-C and UACR were significantly associated with 25OHD after adjusting for other variables. Vitamin D deficiency was independently related to nephropathy after adjusting for confounding variables. CONCLUSION:Vitamin D deficiency was common among Korean T2DM patients; it was independently associated with microalbuminuria and HDL level, and positively related to diabetic nephropathy. 10.3803/EnM.2020.826
    Assessment of renal function in living kidney donors before and after nephrectomy: A Japanese prospective, observational cohort study. Kakuta Yoichi,Imamura Ryoichi,Okumi Masayoshi,Horio Masaru,Isaka Yoshitaka,Ichimaru Naotsugu,Takahara Shiro,Nonomura Norio,Tanabe Kazunari International journal of urology : official journal of the Japanese Urological Association OBJECTIVE:To investigate the utility of estimated glomerular filtration rate for assessing kidney function in living kidney donors before and after nephrectomy. METHODS:A total of 101 donors underwent inulin clearance measurements before and 1 year after nephrectomy. The mean of three inulin clearance values was used as the measured glomerular filtration rate. Estimated glomerular filtration rate based on serum creatinine and cystatin C levels was calculated using the Japanese estimated glomerular filtration rate equation, Chronic Kidney Disease Epidemiology Collaboration formula and new full age spectrum equation. Age-adjusted chronic kidney disease was defined as glomerular filtration rate <75 mL/min/1.73m for donors aged <40 years, <60 mL/min/1.73m for donors aged 40-65 years and <45 mL/min/1.73m for donors aged >65 years. RESULTS:The postoperative measured glomerular filtration rate <60 mL/min/1.73m and age-adjusted chronic kidney disease rate were 36.0% and 27.0%, respectively. In younger donors (aged <50 years), postoperative measured glomerular filtration rate <60 mL/min/1.73m and age-adjusted chronic kidney disease rates were 5.3% and 26.3%, respectively. In older donors (aged >70 years), postoperative measured glomerular filtration rate <60 mL/min/1.73m and age-adjusted chronic kidney disease rates were 75.0% and 33.3%, respectively. Donor age and measured glomerular filtration rate were significant predictors of postoperative measured glomerular filtration rate. The Japanese estimated glomerular filtration rate equation based on creatinine and cystatin C showed the strongest correlation with measured glomerular filtration rate. However, the Japanese estimated glomerular filtration rate equation based on creatinine overestimated the prevalence of measured glomerular filtration rate <60 mL/min/1.73m , whereas the Japanese estimated glomerular filtration rate based on cystatin C underestimated it. CONCLUSIONS:Aged donors might have an increased risk of lower glomerular filtration rate after donor nephrectomy; post-surgery, long-term monitoring of renal function is recommended. Measurement of glomerular filtration rate should be carried out for donors, especially pre-surgery. A more precise glomerular filtration rate equation is required in the future. 10.1111/iju.13923