Background:Acute kidney injury (AKI) is a significant concern in critically ill patients, with mortality and morbidity implications. The serum uric acid-to-albumin ratio has been proposed as a potential prognostic marker for patients with and without AKI. This study aimed to investigate the relationship between this ratio and 28-day mortality in these patient groups. Methods:A retrospective study was conducted on critically ill patients aged over 18, hospitalized in the internal medicine ICU at Osmangazi University, Eskisehir, Turkey, from May 2020 to November 2021. Patients were categorized based on the presence or absence of AKI. The primary outcome was 28-day mortality. The serum uric acid-to-albumin ratio was calculated, and its prognostic value was assessed using Receiver Operating Curve (ROC) analysis. Results:Of the 1,016 patients, 449 had AKI. The mean age was 67.1 ± 15.27 years, with 53.9% being male. The serum uric acid-to-albumin ratio was found to have significant prognostic value in predicting 28-day mortality in both groups. In the overall study group, a ratio of 2.32 mg/g predicted 28-day mortality with 71.1% specificity and 58.3% sensitivity. For patients with AKI, a ratio of 3.59 mg/g predicted mortality with 85.3% specificity and 44% sensitivity. For those without AKI, a ratio of 2.28 mg/g predicted mortality with 84.1% specificity and 39.3% sensitivity. Conclusion:The serum uric acid-to-albumin ratio is a valuable prognostic tool for predicting 28-day mortality in critically ill patients, irrespective of AKI status. Incorporating this low-cost biomarker into scoring systems could enhance patient management and outcome predictions.

OBJECTIVE:We aimed to investigate uric acid and albumin ratio (UA/A) as a marker of short-term mortality in acute kidney injury (AKI). Both uric acid and albumin are strongly correlated with the development and mortality of AKI. METHODS:The patients hospitalized from May 2019 to September 2019 for AKI were included in this study. The diagnostic odds ratio (DOR), Youden index (J), and the area under a receiver operating characteristic curve (AUROC) determined a cut-off UA/A ratio for mortality. Cox-regression analysis was performed to identify UA/A as a prognostic marker of the 30-day mortality rate. RESULTS:A total of 171 patients with an average age of 69.20±13.0 (45.6% women) were included in the study. The average UA/A ratio was 3.3±1.5 mg/g and 2.5±1.0 mg/g in the non-survivor and survivor groups, respectively (P=0.001). The best cut-off UA/A ratio associated with mortality was determined as 2.4 mg/g with a specificity of 52% and a sensitivity of 77% (DOR, 3.6; J, 28.8; AUROC, 0.644). Thirty-day cumulative survival rates of the low and high UA/A ratio groups were 85.9±4.0% and 63.7±5.0%, respectively. The estimated survival times of the low and high UA/A ratio groups were 27.7 days (95% confidence interval [CI], 26.2-29.3) and 23.9 days (95% Cl, 22.0-25.9), respectively. CONCLUSION:We found a direct correlation between 30-day mortality and UA/A ratio at initial presentation in AKI patients regardless of age, comorbidities, and clinical and laboratory findings, including albuminuria.

Outpatient renal stone formers belonging to the established urolithiasis subgroups and controls were examined with respect to urinary and serum citrate (Cit) and several associated variables. Only in the normocalciuric majority of calcium and in uric acid stone formers was Cit in 24-hour urine decreased, but was normal in 2-hour fasting morning, and in 3-hour postprandial urine following a Cit-free test meal. Serum Cit was elevated in normocalciuria, renal and resorptive hypercalciuria. This Cit constellation was associated with either normal (absorptive, renal hypercalciuria) or low (normocalciuria, uric acid stone formers) parathyroid gland function as assessed by serum parathyroid hormone and nephrogenous urinary cyclic AMP, except in patients with primary hyperparathyroidism. In 2-hour morning urine the magnesium/creatinine ratio (normocalciuria) and ammonia excretion (uric acid stone formers) were decreased, while ammonia in 24-hour urine was low in all stone formers. It is suggested that Cit metabolism is altered in renal stone disease in general, and that in normocalciuria, stone inhibitors (Cit; magnesium) may be deficient.

High concentration of citrate exists in bone of humans and all osteo-vertebrates, and citrate incorporation imparts important biomechanical and other functional properties to bone. However, which cells are responsible for citrate production in bone remains unclear and whether the citrate component changes with bone loss during osteoporosis is also not known. Here, we show that the citrate content is markedly reduced in the bone of mice or rats with age-related, ovariectomy-induced or retinoic acid-induced bone loss. Plasmic citrate is also downregulated in osteoporotic animals. Importantly, the plasmic citrate level of aged osteoporotic males is significantly lower than that of young healthy males and positively correlates with human lumbar spine bone mineral density (BMD) and total hip BMD. Furthermore, citrate production increases with in vitro osteoblastic differentiation, accompanied by upregulation of proteins involved in citrate secretion, suggesting that osteoblasts are highly specialized cells that produce citrate in bone. Our findings establish a novel relationship between citrate content and bone loss-related diseases such as osteoporosis, suggesting a critical role of bone citrate in the maintenance of the citrate balance in the circulation. Serum citrate level may thus represent a novel marker for osteoporosis.

Experimental models suggest an important role for mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD) and acute kidney injury (AKI), but little is known regarding the impact of common mitochondrial genetic variation on kidney health. We sought to evaluate associations of inherited mitochondrial DNA (mtDNA) variation with risk of CKD and AKI in a large population-based cohort. We categorized UK Biobank participants who self-identified as white into eight distinct mtDNA haplotypes, which were previously identified based on their associations with phenotypes associated with mitochondrial DNA copy number, a measure of mitochondrial function. We used linear and logistic regression models to evaluate associations of these mtDNA haplotypes with estimated glomerular filtration rate by serum creatinine and cystatin C (eGFR, N = 362,802), prevalent (N = 416 cases) and incident (N = 405 cases) end-stage kidney disease (ESKD), AKI defined by diagnostic codes (N = 14,170 cases), and urine albumin/creatinine ratio (ACR, N = 114,662). The mean age was 57 ± 8 years and the mean eGFR was 90 ± 14 ml/min/1.73 m. MtDNA haplotype was significantly associated with eGFR (p = 2.8E-12), but not with prevalent ESKD (p = 5.9E-2), incident ESKD (p = 0.93), AKI (p = 0.26), or urine ACR (p = 0.54). The association of mtDNA haplotype with eGFR remained significant after adjustment for diabetes mellitus and hypertension (p = 1.2E-10). When compared to the reference haplotype, mtDNA haplotypes I (β = 0.402, standard error (SE) = 0.111; p = 2.7E-4), IV (β = 0.430, SE = 0.073; p = 4.2E-9), and V (β = 0.233, SE = 0.050; p = 2.7E-6) were each associated with higher eGFR. Among self-identified white UK Biobank participants, mtDNA haplotype was associated with eGFR, but not with ESKD, AKI or albuminuria.

OBJECTIVES:This study aimed to assess the current incidence and risk factors for polymyxin B-associated acute kidney injury (AKI) in Chinese hospitals for a more effective clinical use for polymyxin B. METHODS:This multicenter, retrospective cohort study included patients from 14 Chinese teaching hospitals who received polymyxin B therapy. Univariate and multivariate logistic regression models were used to determine the factors associated with polymyxin B-associated incident AKI. Furthermore, a multivariate logistic regression model was used to identify the independent risk factors for AKI. RESULTS:A total of 251 patients were included in the analysis. The overall incidence of AKI was 33.5%. A multivariate logistic regression model identified the loading dose (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.01-3.38; P = 0.0491) and the use of two or more nephrotoxic drugs (HR, 3.56; 95% CI, 1.55-8.18; P = 0.0029) as independent risk factors for the occurrence of AKI. Meanwhile, the estimated glomerular filtration rate had a protective effect (HR, 0.99; 95% CI, 0.98-0.99; P = 0.0006) on the occurrence of AKI. The daily dose, cumulative dose, and treatment duration of polymyxin B did not affect the occurrence of AKI. CONCLUSIONS:The use of polymyxin B loading doses and the combined use of multiple nephrotoxic drugs are independent risk factors for polymyxin B-associated AKI. The severity of AKI may be higher in patients with elevated baseline creatinine levels.

PURPOSE:The incidence, patient features, risk factors and outcomes of surgery-associated postoperative acute kidney injury (PO-AKI) across different countries and health care systems is unclear. METHODS:We conducted an international prospective, observational, multi-center study in 30 countries in patients undergoing major surgery (> 2-h duration and postoperative intensive care unit (ICU) or high dependency unit admission). The primary endpoint was the occurrence of PO-AKI within 72 h of surgery defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints included PO-AKI severity and duration, use of renal replacement therapy (RRT), mortality, and ICU and hospital length of stay. RESULTS:We studied 10,568 patients and 1945 (18.4%) developed PO-AKI (1236 (63.5%) KDIGO stage 1500 (25.7%) KDIGO stage 2209 (10.7%) KDIGO stage 3). In 33.8% PO-AKI was persistent, and 170/1945 (8.7%) of patients with PO-AKI received RRT in the ICU. Patients with PO-AKI had greater ICU (6.3% vs. 0.7%) and hospital (8.6% vs. 1.4%) mortality, and longer ICU (median 2 (Q1-Q3, 1-3) days vs. 3 (Q1-Q3, 1-6) days) and hospital length of stay (median 14 (Q1-Q3, 9-24) days vs. 10 (Q1-Q3, 7-17) days). Risk factors for PO-AKI included older age, comorbidities (hypertension, diabetes, chronic kidney disease), type, duration and urgency of surgery as well as intraoperative vasopressors, and aminoglycosides administration. CONCLUSION:In a comprehensive multinational study, approximately one in five patients develop PO-AKI after major surgery. Increasing severity of PO-AKI is associated with a progressive increase in adverse outcomes. Our findings indicate that PO-AKI represents a significant burden for health care worldwide.

INTRODUCTION:Acute kidney injury (AKI) is frequent in critically ill COVID-19 patients and is associated with a higher mortality risk. By increasing intrathoracic pressure, positive pressure ventilation (PPV) may reduce renal perfusion pressure by reducing venous return to the heart or by increasing renal venous congestion. This study's aim was to evaluate the association between AKI and haemodynamic and ventilatory parameters in COVID-19 patients with ARDS. METHODS:This is a single-centre retrospective observational study. Consecutive patients diagnosed with COVID-19 who met ARDS criteria and required invasive mechanical ventilation were enrolled. The relationship between respiratory and haemodynamic parameters influenced by PPV and AKI development was evaluated. AKI was defined according to KDIGO criteria. AKI recovery was evaluated a month after ICU admission and patients were classified as "recovered," if serum creatinine (sCr) value returned to baseline, or as having "acute kidney disease" (AKD), if criteria for AKI stage 1 or greater persisted. The 6-month all-cause mortality was collected. RESULTS:A total of 144 patients were included in the analysis. AKI occurred in 69 (48%) patients and 26 (18%) required renal replacement therapy. In a multivariate logistic regression analysis, sex, hypertension, cumulative dose of furosemide, fluid balance, and plateau pressure were independently associated with AKI. Mortality at 6 months was 50% in the AKI group and 32% in the non-AKI group (p = 0.03). Among 36 patients who developed AKI and were discharged alive from the hospital, 56% had a full renal recovery after a month, while 14%, 6%, and 14% were classified as having an AKD of stage 0, 2, and 3, respectively. CONCLUSIONS:In our cohort, AKI was independently associated with multiple variables, including high plateau pressure, suggesting a possible role of PPV on AKI development. Further studies are needed to clarify the role of mechanical ventilation on renal function.

PURPOSE:It is unclear whether preoperative serum uric acid (SUA) elevation may play a role in the development of acute kidney injury (AKI) associated with cardiac surgery (CSA-AKI). We conducted a cohort study to evaluate the influence of preoperative hyperuricemia on AKI in patients at high risk for developing SC-AKI. DESIGN:Multicenter prospective international cohort study. SETTING:Fourteen university hospitals in Spain and the United Kingdom. PARTICIPANTS:We studied 261 consecutive patients at high risk of developing CSA-AKI, according to a Cleveland score ≥ 4 points, from July to December 2017. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:AKIN criteria were used for the definition of AKI. Multivariable logistic regression models and propensity score-matched pairwise analysis were used to determine the adjusted association between preoperative hyperuricemia (≥7 mg/dL) and AKI. Elevated preoperative AUS (≥7 mg/dL) was present in 190 patients (72.8%), whereas CSA-AKI occurred in 145 patients (55.5%). In multivariable logistic regression models, hyperuricemia was not associated with a significantly increased risk of AKI (adjusted Odds Ratio [OR]: 1.58; 95% confidence interval [CI]: 0.81-3; P = .17). In propensity score-matched analysis of 140 patients, the hyperuricemia group experienced similar adjusted odds of AKI (OR 1.05, 95%CI 0.93-1.19, P = .37). CONCLUSIONS:Hyperuricemia was not associated with an increased risk of AKI in this cohort of patients undergoing cardiac surgery at high risk of developing CSA-AKI.

The risk factors, especially laboratory indicators, of prognosis after acute kidney injury (AKI) remain unclear. We conducted a retrospective survey of Chinese People's Liberation Army General Hospital from January 1, 2012 to December 31, 2012 according to the AKI diagnosis standard issued by Kidney Disease Improving Global Outcomes. The epidemiological features and factors influencing hospital mortality and renal function recovery were evaluated through logistic regression analysis. Among 77 662 cases of hospitalized patients, 1387 suffered from AKI. The incidence rate and mortality of AKI were 1.79% and 14.56%, respectively. Multivariate logistic regression analysis revealed that high AKI stage, age greater than 80 years, neoplastic disease, low cardiac output, increased white blood cell count, and decreased platelet count and serum albumin levels were the risk factors affecting the mortality of AKI patients. Conversely, body mass index between 28 and 34.9 was a protective factor. Increased AKI stage, tumor disease, post-cardiopulmonary resuscitation, and RRT were the risk factors of renal function recovery upon discharge. In addition to traditional risk factors, white blood cell count, platelet count, albumin, and BMI were the predictors of the mortality of AKI patients. No laboratory indicators were found to be the risk factors of renal function recovery in AKI patients.

BACKGROUND:Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS:In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS:We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. CONCLUSIONS:Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.).