Lipid Accumulation and Chronic Kidney Disease.
Gai Zhibo,Wang Tianqi,Visentin Michele,Kullak-Ublick Gerd A,Fu Xianjun,Wang Zhenguo
Nutrients
Obesity and hyperlipidemia are the most prevalent independent risk factors of chronic kidney disease (CKD), suggesting that lipid accumulation in the renal parenchyma is detrimental to renal function. Non-esterified fatty acids (also known as free fatty acids, FFA) are especially harmful to the kidneys. A concerted, increased FFA uptake due to high fat diets, overexpression of fatty acid uptake systems such as the CD36 scavenger receptor and the fatty acid transport proteins, and a reduced β-oxidation rate underlie the intracellular lipid accumulation in non-adipose tissues. FFAs in excess can damage podocytes, proximal tubular epithelial cells and the tubulointerstitial tissue through various mechanisms, in particular by boosting the production of reactive oxygen species (ROS) and lipid peroxidation, promoting mitochondrial damage and tissue inflammation, which result in glomerular and tubular lesions. Not all lipids are bad for the kidneys: polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to help lag the progression of chronic kidney disease (CKD). Lifestyle interventions, especially dietary adjustments, and lipid-lowering drugs can contribute to improve the clinical outcome of patients with CKD.
10.3390/nu11040722
Association of metabolic syndrome and chronic kidney disease.
Obesity reviews : an official journal of the International Association for the Study of Obesity
The prevalence of kidney disease is increasing rapidly worldwide, reflecting rising rates of obesity, diabetes, and associated metabolic syndrome (MetS). Chronic kidney disease and related comorbidities such as obesity, diabetes, and hypertension place a significant financial burden on healthcare systems. Despite the widespread use of RAAS inhibitors, intensive blood pressure and glycemic control, and newer therapeutic options consisting of sodium/glucose cotransporter-2 (SGLT-2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists, a significant risk of progression to end-stage renal disease remains in the high-risk obese and diabetic population. The MetS is a cluster of cardiovascular risk factors that adversely affect the development and progression of chronic kidney failure. According to the criteria of the World Health Organization, it is defined by visceral adiposity, impaired glucose tolerance or insulin resistance, atherogenic dyslipidemia, raised blood pressure, and microalbuminuria with a albumin-to-creatinine ratio ≥30 mg/g. At molecular level MetS is marked by a proinflammatory state and increased oxidative stress leading to various pathophysiological changes causing endothelial dysfunction and a hypercoagulable state. Because the kidney is a highly vascularized organ, it is especially susceptible for those microvascular changes. Therefore, the MetS and its individual components are associated with the premature development, acceleration, and progression of chronic kidney disease. Therefore, it is becoming increasingly important to elucidate the underlying mechanisms of MetS-associated chronic kidney disease in order to develop new strategies for preventing and slowing the progression of renal disease. In this review, we will elucidate (i) the renal structural, hemodynamic, and metabolic changes that occur in obesity and obesity-related kidney injury; (ii) the clinicopathological characteristics of obesity-related kidney injury, primarily focusing on obesity-associated glomerulopathy; (iii) the potential additional factors or predisposing factors that may turn patients more susceptible to renal structural or functional compensatory failure and subsequent injury.
10.1111/obr.13649
Degree of joint risk factor control and incident chronic kidney disease among individuals with obesity.
Diabetes, obesity & metabolism
AIM:To investigate the extent to which joint risk factor control might attenuate the excess risk of chronic kidney disease (CKD) in participants with obesity. PATIENTS AND METHODS:We included a total of 97 538 participants who were obese at baseline and matched 97 538 normal weight control participants from the UK Biobank in the analysis. The degree of joint risk factor control was assessed based on six major CKD risk factors, including blood pressure, glycated haemoglobin, low-density lipoprotein cholesterol, albuminuria, smoking and physical activity. The Cox proportional hazards models were used to estimate associations between the degree of risk factor control and risk of CKD, following participants from their baseline assessment until the occurrence of CKD, death, or the end of the follow-up period. RESULTS:Among participants with obesity, joint risk factor control showed an association with a stepwise reduction of incident CKD risk. Each additional risk factor control corresponded to an 11% (hazard ratio: 0.89; 95% confidence interval: 0.86-0.91) reduced risk of CKD among participants with obesity, with the optimal controlling of all six risk factors associated with a 49% (hazard ratio: 0.51; 95% confidence interval: 0.43-0.61) decrease in risk of CKD. Furthermore, in individuals with obesity who jointly controlled all six risk factors, the excess risk of CKD associated with obesity was effectively neutralized compared with normal weight control subjects. Notably, the protective correlations between the degree of joint risk factor control and the incidence of CKD were more pronounced in men compared with women, in individuals with a lower healthy food score versus a higher score, and among diabetes medication users as opposed to non-users (p = 0.017, 0.033 and 0.014, respectively). CONCLUSION:The joint risk factor control is associated with an inverse association of CKD risk in an accumulative manner among individuals with obesity. Achieving ideal control over risk factors may effectively counterbalance the excessive risk of CKD typically associated with obesity.
10.1111/dom.15874
How obesity and metabolic syndrome affect cardiovascular events, progression to kidney failure and all-cause mortality in chronic kidney disease.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
BACKGROUND:Obesity and metabolic syndrome (MetS) are prevalent among chronic kidney disease (CKD) patients. However, it is unclear whether obesity without MetS is associated with a higher risk of adverse clinical outcomes in CKD patients. METHODS:We searched the National Health Insurance Service database of Korea for patients who underwent national health screenings in 2009-11 and identified 59 725 CKD patients. Obesity was defined as a body mass index ≥25 kg/m2. MetS was defined as the presence of three or more metabolic risks. RESULTS:The cumulative event rate of cardiovascular (CV) events, progression to end-stage kidney disease (ESKD) and all-cause mortality was the lowest among obese patients without MetS (all P < .001). In multivariable analysis, obese (versus non-obese) patients without MetS were not at increased risks of CV events [adjusted hazard ratio (HR) 1.02 (95% confidence interval 0.94-1.11)] or progression to ESKD [0.92 (0.77-1.09)]. Their risk of all-cause mortality was significantly decreased [0.82 (0.75-0.90)]. These findings were consistently observed in overweight, obese and morbidly obese patients without MetS. Moreover, despite a linear increase in HR for each additional metabolic abnormality in both obese and non-obese patients, the slope of HR increase for CV events was significantly slower in obese patients (P for interaction = .038). CONCLUSIONS:Obesity without MetS did not increase the risk of CV complications or progression to ESKD. The healthy effect of obesity on all-cause mortality risk and its weakening effect on the association between metabolic hazards and CV risk should be considered in CKD patients.
10.1093/ndt/gfad214
Renal Endocannabinoid Dysregulation in Obesity-Induced Chronic Kidney Disease in Humans.
International journal of molecular sciences
The endocannabinoid system (ECS) regulates various physiological processes, including energy homeostasis and kidney function. ECS upregulation in obese animals and humans suggests a potential link to obesity-induced chronic kidney disease (CKD). However, obesity-induced ECS changes in the kidney are mainly studied in rodents, leaving the impact on obese humans unknown. In this study, a total of 21 lean and obese males (38-71 years) underwent a kidney biopsy. Biochemical analysis, histology, and endocannabinoid (eCB) assessment were performed on kidney tissue and blood samples. Correlations between different parameters were evaluated using a comprehensive matrix. The obese group exhibited kidney damage, reflected in morphological changes, and elevated kidney injury and fibrotic markers. While serum eCB levels were similar between the lean and obese groups, kidney eCB analysis revealed higher anandamide in obese patients. Obese individuals also exhibited reduced expression of cannabinoid-1 receptor (CB1R) in the kidney, along with increased activity of eCB synthesizing and degrading enzymes. Correlation analysis highlighted connections between renal eCBs, kidney injury markers, obesity, and related pathologies. In summary, this study investigates obesity's impact on renal eCB "tone" in humans, providing insights into the ECS's role in obesity-induced CKD. Our findings enhance the understanding of the intricate interplay among obesity, the ECS, and kidney function.
10.3390/ijms241713636
Recent advances in the treatment of patients with obesity and chronic kidney disease.
Annals of medicine
Obesity is a chronic disease characterised by excess adiposity, which impairs health. The high prevalence of obesity raises the risk of long-term medical complications including type 2 diabetes and chronic kidney disease. Several studies have focused on patients with obesity, type 2 diabetes and chronic kidney disease due to the increased prevalence of diabetic kidney disease. Several randomized controlled trials on sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 analogues, and bariatric surgery in diabetic kidney disease showed renoprotective effects. However, further research is critical to address the treatment of patients with obesity and chronic kidney disease to lessen morbidity.Key messageObesity is a driver of chronic kidney disease, and type 2 diabetes, along with obesity, accelerates chronic kidney disease.Several randomized controlled trials on sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 analogues, and bariatric surgery in diabetic kidney disease demonstrate the improvement of renal outcomes.There is a need to address the treatment of patients with obesity and CKD to lessen morbidity.
10.1080/07853890.2023.2203517
Anti-obesity pharmacotherapy in adults with chronic kidney disease.
Kidney international
Obesity is a leading risk factor for the development and progression of kidney disease and a major barrier to optimal management of patients with chronic kidney disease. While in the past anti-obesity drugs offered only modest weight loss efficacy in exchange for various safety and tolerability risks, a wave of safer, more tolerable, and more effective treatment options is transforming the management of obesity. This review evaluates current and future pharmacologic anti-obesity therapy in adults through a kidney-oriented lens. It also explores the goals of anti-obesity treatment, describes the underlying putative mechanisms of action, and raises important scientific questions that deserve further exploration in people with chronic kidney disease.
10.1016/j.kint.2023.10.014
Obesity Management and Chronic Kidney Disease.
Chen Yang,Dabbas Walaa,Gangemi Antonio,Benedetti Enrico,Lash James,Finn Patricia W,Perkins David L
Seminars in nephrology
Obesity is one of the risk factors for the development and progression of chronic kidney disease (CKD). Several studies have shown the association between increased body mass index and kidney function decline. Obesity leads to CKD directly by acting as an independent risk factor and indirectly through increasing risks for diabetes, hypertension, and atherosclerosis, a group of well-established independent risk factors for CKD. Alterations in renal hemodynamics, inflammation, and in hormones and growth factors results in hyperfiltration injury and focal segmental glomerulosclerosis. In recent years, many studies have shown that the gut microbiome may play a role in the pathogenesis of obesity. Dysbiosis has been noted in obese subjects in both human and animal studies. Changes in the gut microbiome in obese patients promote weight gain by effectively extracting energy from diet, and induction of low-grade inflammation. Evidence also points to the role of inflammation within the adipose tissue in obesity as a key factor in the pathogenesis of obesity-related complications. Thus, obesity is the net result of complex interactions between behavioral, genetic, and environmental factors. In terms of management, conservative approaches are often the first option, but they often are unsuccessful in achieving and/or maintaining weight loss, particularly in severe obesity. Consequently, nonmedical management with bariatric surgery is the most effective treatment option for morbid obesity and has shown mitigation of multiple risk factors for the progression of CKD. The most frequently performed interventions are vertical sleeve gastrectomy and Roux-en-Y gastric bypass. Studies have shown that bariatric surgery is associated with beneficial effects on CKD by mitigating its risk factors by weight loss, reducing insulin resistance, hemoglobin A1c, and proteinuria, in addition to positive long-term outcomes. Because of the epidemic of obesity, the prevalence of obesity in kidney transplant recipients also is increasing. The maximal body mass index (BMI) threshold for kidney transplantation is not clear. The Organ Procurement Transplant Network/Scientific Registry of Transplant Recipients 2019 annual data report showed that the proportion of kidney transplant recipient candidates with a BMI of 30 kg/m or greater is increasing steadily. Morbid obesity is linked to adverse graft outcomes including delayed graft function, primary nonfunction, and decreased graft survival. Obesity is also an independent risk factor for cardiovascular death in kidney transplant recipients, suggesting that these patients should not be excluded from transplantation based on their BMI because transplantation is associated with lower mortality compared with dialysis. However, many centers exclude obese patients (with different BMI cut-off values) from transplantation to avoid postoperative complications. To minimize the surgical complications of kidney transplantation in obese patients, our center has adopted the robot-assisted kidney transplantation procedure. Our data show that this approach is comparable with historical nonobese controls in the United Network for Organ Sharing database in terms of patient and graft survival. Another surgical option for this group of patients at our center is a combined robotic sleeve gastrectomy and robotic-assisted kidney transplant. In a recent study, this approach showed promising results in terms of weight loss, patient survival, and graft survival, and might become more common in the future.
10.1016/j.semnephrol.2021.06.010
Obesity and chronic kidney disease.
Nehus Edward
Current opinion in pediatrics
PURPOSE OF REVIEW:To review recent advances in the epidemiology, pathophysiology, clinical features, and treatment of obesity-related kidney disease. RECENT FINDINGS:Studies have confirmed that obesity is associated with increased risk of developing chronic kidney disease (CKD). This risk extends to those who are metabolically healthy, indicating that obesity per se contributes to CKD independent of the metabolic syndrome. Recent developments in the pathophysiology of obesity-related kidney disease indicate that chronic inflammation and abnormal lipid metabolism contribute to kidney cell injury. Children with severe obesity have increased prevalence of early kidney abnormalities, including albuminuria, decreased kidney function, and elevated biomarkers of early kidney injury. For these patients, bariatric surgery has emerged as a treatment option to consider. Longitudinal studies in children and adults have demonstrated that in patients with obesity-related kidney disease, kidney function and albuminuria improve following bariatric surgery. SUMMARY:The injurious renal effects of obesity are present in childhood, although the natural history and clinical spectrum of obesity-related kidney disease in children are not known. In obese children with early kidney disease, identification of kidney injury, implementation of preventive strategies, and prompt treatment are essential to improving clinical outcomes.
10.1097/MOP.0000000000000586
Obesity and chronic kidney disease.
American journal of physiology. Endocrinology and metabolism
The prevalence of obesity has increased dramatically during the past decades, which has been a major health problem. Since 1975, the number of people with obesity worldwide has nearly tripled. An increasing number of studies find obesity as a driver of chronic kidney disease (CKD) progression, and the mechanisms are complex and include hemodynamic changes, inflammation, oxidative stress, and activation of the renin-angiotensin-aldosterone system (RAAS). Obesity-related kidney disease is characterized by glomerulomegaly, which is often accompanied by localized and segmental glomerulosclerosis lesions. In these patients, the early symptoms are atypical, with microproteinuria being the main clinical manifestation and nephrotic syndrome being rare. Weight loss and RAAS blockers have a protective effect on obesity-related CKD, but even so, a significant proportion of patients eventually progress to end-stage renal disease despite treatment. Thus, it is critical to comprehend the mechanisms underlying obesity-related CKD to create new tactics for slowing or stopping disease progression. In this review, we summarize current knowledge on the mechanisms of obesity-related kidney disease, its pathological changes, and future perspectives on its treatment.
10.1152/ajpendo.00179.2022
Obesity, Chronic Kidney Disease, and Kidney Transplantation: An Evolving Relationship.
Azhar Ambreen,Hassan Nabeel,Tapolyai Mihaly,Molnar Miklos Z
Seminars in nephrology
Obesity has a fundamental role in driving the global kidney disease burden. The perplexing relationship of obesity with chronic kidney disease remains debated. However, a thorough understanding of the interplay of obesity in conjunction with chronic kidney disease and appropriate management options is lacking, leading to further increases in morbidity and mortality. Moreover, underutilization of bariatric procedures and unrealistic expectations of weight reduction based on body mass index, leading to poor access to kidney transplantation, are fueling the fire. In this review, we summarize the available data related to the obesity and chronic kidney disease association and its novel management options.
10.1016/j.semnephrol.2021.03.013
Obesity and chronic kidney disease.
Eknoyan G
Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia
Obesity is associated with the early onset of glomerulomegaly, hemodynamic changes of a hyperfiltering kidney, and increased albuminuria, which are potentially reversible with weight loss. However, pathologic lesions of focal segmental glomerulosclerosis develop in experimental models of sustained obesity, and are observed in morbidly obese humans presenting with massive proteinuria. In addition, several observational, cross sectional and longitudinal studies document that obesity is as an independent risk factor for the onset, aggravated course, and poor outcomes of chronic kidney disease, even after adjustment for confounding co-morbidities including metabolic syndrome, diabetes and hypertension, the major causes of chronic kidney disease. Early dietary intervention to reduce weight, and where necessary bariatric surgery, should be considered in the management of overweight and obese chronic kidney disease (CKD) patients.
10.3265/Nefrologia.pre2011.May.10963