This study aimed to comprehensively assess epidemiologic evidence on the relation between obesity and kidney disease (KD). From 247 retrieved articles via PubMed (1980-2006), 25 cohorts, 3 cross-sectional, and 19 case-control studies met inclusion criteria. Related data were extracted using a standardized protocol. We estimated the pooled relative risk (RR) and 95% confidence interval (95% CI) of KD for each body mass index (BMI) category compared with normal weight using meta-analysis models. Population attributable risk was also calculated. Compared with normal-weight individuals (18.5<BMI<25), overweight individuals (25< or =BMI<30) had elevated risk for KD (RR=1.40; 95% CI 1.30-1.50); obese individuals were at much higher risk (RR=1.83 (1.57-2.13)). Obesity in women was associated with a higher risk than in men (RR=1.92 (1.78-2.07) vs 1.49 (1.36-1.63); P<0.001). Results from cohort studies in patient populations and cross-sectional and case-control studies all indicated a positive association between BMI and risks for KD outcomes. We estimated that 24.2% and 33.9% of KD cases among US men and women, respectively, and in industrialized countries, 13.8% in men and 24.9% in women, could be related to overweight and obesity. Obesity increases the risk for KD in the general population, and the association appears to be stronger in women than in men. Obesity adversely affects the progress of KD among patients with kidney-related diseases.

Obesity is becoming an epidemic in the United States and worldwide and increases risk for many diseases, particularly insulin resistance, type 2 diabetes mellitus, and cardiovascular disease. The mechanisms linking obesity with these diseases remain incompletely understood. Over the past 2 to 3 decades, it has been recognized that in obesity, inflammation, with increased accumulation and inflammatory polarization of immune cells, takes place in various tissues, including adipose tissue, skeletal muscle, liver, gut, pancreatic islet, and brain and may contribute to obesity-linked metabolic dysfunctions, leading to insulin resistance and type 2 diabetes mellitus. Therapies targeting inflammation have shed light on certain obesity-linked diseases, including type 2 diabetes mellitus and atherosclerotic cardiovascular disease, but remain to be tested further and confirmed in clinical trials. This review focuses on inflammation in adipose tissue and its potential role in insulin resistance associated with obesity.

Diabetic nephropathy is a major long-term complication of diabetes mellitus and one of the most common causes of end-stage renal disease. Thickening of the glomerular basement membrane, glomerular cell hypertrophy and podocyte loss are among the main pathological changes that occur during diabetic nephropathy, resulting in proteinuria. Injury to podocytes, which are a crucial component of the glomerular filtration barrier, seems to play a key role in the development of diabetic nephropathy. Recent studies have suggested that dysregulation of AMP-activated kinase protein, which is an essential cellular energy sensor, may play a fundamental role in this process. The purpose of this review is to highlight the molecular mechanisms associated with AMP-activated protein kinase (AMPK) in podocytes that are involved in the pathogenesis of diabetic nephropathy.© 2019 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

随着肥胖的全球流行，肥胖相关性肾病（ORG）发生率明显增高。ORG临床表现为不同程度的蛋白尿，少数患者进展至慢性肾功能不全甚至终末期肾病。ORG的发生与血流动力学异常、肾素-血管紧张素-醛固酮系统激活、胰岛素抵抗、脂代谢紊乱、脂肪细胞因子紊乱、微炎症作用等有关。其治疗方案多样，包括减轻体质量、降压、调节代谢等。本文对ORG的发病机制及治疗新进展，包括靶向治疗做一综述。

目的 通过评估高脂饮食（high-fat diet，HFD）诱导的肥胖相关肾病C57BL/6J小鼠肾周脂肪组织炎症，进一步探讨其可能机制。 方法 将12只8~10周龄雄性C57BL/6J小鼠，采用简单随机抽样方法分为正常饲料饮食组（ND组，n=6）和高脂饲料饮食组（HFD组，n=6），喂养14周后，采集血液，剥离双肾，HE、PAS、Masson染色观察肾脏及肾周脂肪的病理改变；实时荧光定量PCR法检测肾周脂肪肿瘤坏死因子α（TNF-α）、M1型巨噬细胞标志物CD11c、白细胞介素（IL）-1β、单核细胞趋化蛋白-1（MCP-1）、IL-10、转化生长因子-β1、M2型巨噬细胞标志物CD206、纤维连接蛋白1 mRNA的表达量；免疫组化法检测肾脏及肾周脂肪巨噬细胞标志物F4/80、CD68及白细胞共同抗原（leukocyte common antigen，LCA）的表达。 结果 喂养14周后，HFD组体重明显高于ND组[（35.83±1.19）g比（24.06±0.37）g，P&lt;0.05]。HFD组小鼠肾周脂肪细胞增生肥大，并伴有肾小球增生肥大、系膜基质增生扩张及肾间质纤维化等病理学改变（均P&lt;0.05），随机血糖、血脂、血肌酐及尿素氮水平明显高于ND组（均P&lt;0.05）。肾周脂肪组织M1型巨噬细胞相关TNF-α、CD11c、IL-1β、MCP-1的mRNA相对表达量明显高于ND组（均P&lt;0.05），且免疫组化显示HFD组肾周脂肪组织F4/80、CD68 及LCA的表达亦显著高于ND组（均P&lt;0.05），表明HFD组肾周脂肪巨噬细胞和炎细胞显著多于ND组。Pearson相关分析结果显示，肾周脂肪平均面积与肾周脂肪组织内巨噬细胞数量、肾小球截面积等多个形态学指标以及尿素氮等肾功能指标呈正相关（均P&lt;0.05）。 结论 高脂饮食诱导的肥胖相关肾病C57BL/6J小鼠模型建模成功，且肾周脂肪组织确实存在明显的炎性反应，巨噬细胞发生明显极化，主要向M1型巨噬细胞促炎方向极化。

Unlike native high-density lipoprotein (HDL), oxidized HDL exerts adverse effects in a number of diseases, including chronic kidney disease (CKD); however, the mechanisms involved in this process remain unclear. In the present study, we investigated the effects of oxidized HDL on renal tubular cells, which play an important role in the progression of CKD. Human renal proximal tubule epithelial cells (HK-2) were cultured and stimulated with various concentrations of oxidized HDL in the absence or presence of CD36 siRNA. The results revealed that oxidized HDL enhanced the production of reactive oxygen species (ROS) and upregulated the expression of pro-inflammatory factors in the HK-2 cells in a dose-dependent manner. Incubation with oxidized HDL also increased the apoptosis of the HK-2 cells and reduced their migration ability in a dose‑dependent manner. Src family kinase, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) were activated following stimulation with oxidized HDL. All these effects mediated by oxidized HDL on HK-2 cells were markedly attenuated by transfection with with CD36 siRNA pior to stimulation with oxidized HDL. These findings suggest that oxidized HDL enhances the pro-inflammatory properties and impairs the function of HK-2 cells, mainly through the scavenger receptor, CD36, as well as through the Src, MAPK and NF-κB pathways.

Obesity is an independent risk factor for chronic kidney disease (CKD). The mechanisms linking obesity and CKD include systemic changes such as high blood pressure and hyperglycemia, and intrarenal effects relating to lipid accumulation. Normal lipid metabolism is integral to renal physiology and disturbances of renal lipid and energy metabolism are increasingly being linked with kidney disease. AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) are important regulators of fatty acid oxidation, which is frequently abnormal in the kidney with CKD. A high fat diet reduces renal AMPK activity, thereby contributing to reduced fatty acid oxidation and energy imbalance, and treatments to activate AMPK are beneficial in animal models of obesity-related CKD. Studies have found that the specific cell types affected by excessive lipid accumulation are proximal tubular cells, podocytes, and mesangial cells. Targeting disturbances of renal energy metabolism is a promising approach to addressing the current epidemic of obesity-related kidney disease.

Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet-host-microbe interactions.

The feasibility and benefits of lifestyle intervention in chronic kidney disease (CKD) patients who are obese has not been well studied. We examined the early effects of an exercise plus weight loss intervention on body composition, exercise capacity, metabolic parameters and kidney function in obese subjects with CKD.Nine subjects (median age 57 years, body mass index (BMI) 43.9) underwent a lifestyle intervention program that included supervised aerobic exercise (i.e. ∼85% maximum heart rate) and dietary counseling (500 kcal reduction in daily caloric intake). Body composition (iDXA), exercise capacity (maximal oxygen consumption), quality of life, insulin resistance (Matsuda index), inflammation (high sensitivity C-reactive protein), adipokines (leptin and total adiponectin) and kidney function (iothalamate glomerular filtration rate) were measured at baseline and after 12 weeks of the intervention. Changes in parameters were compared using the Wilcoxon signed-rank test.After 12 weeks of intervention, there was a significant decrease in BMI and fat mass (median -4.9 kg (25th-75th percentile -5.9 to -3.0)). There was a significant increase in exercise capacity (3.7 ml/kg/min (3.0-4.7)), along with improvements in insulin sensitivity (0.55 (0.43-1.2)), total adiponectin (780.9 μg/ml (262.1-1,497.1)) and leptin (-5.1 ng/ml (-14.5 to -3.3)). There were improvements in biomarkers of kidney disease very quality of life measures, but kidney function remained unchanged.Lifestyle modification is feasible in obese patients with CKD and produces weight loss that is related to improvements in exercise capacity, insulin resistance and adipokines. Whether lifestyle-induced weight loss and fitness can be sustained and whether it will mediate improvements in kidney function over time merits further investigation.© 2015 S. Karger AG, Basel.

Obesity-related glomerulopathy (ORG) and other obesity-associated kidney diseases pose a major challenge to the treating nephrologist. We review the benefits of weight loss and optimal management of ORG and kidney disease in the setting of obesity. Therapeutic strategies in ORG were limited mainly in the past to weight loss through lifestyle interventions and bariatric surgery, antihypertensive treatment, and renin-angiotensin-aldosterone system blockade. Current approaches to obtain the desired weight loss include novel pharmacologic therapies that have been approved for the treatment of diabetes while offering kidney protection, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1-receptor agonists. This review focuses on the nephroprotective role of the renin-angiotensin-aldosterone system blockade and of these new pharmacologic agents, and on the renal effects of bariatric surgery in chronic kidney disease.Copyright © 2021. Published by Elsevier Inc.

Obesity prevalence continues to increase worldwide, accompanied by a rising tide of hypertension, diabetes, and chronic kidney disease (CKD). Although body mass index is typically used to assess obesity in clinical practice, altered body composition (eg, reduced muscle mass and increased visceral adiposity) are common among patients with CKD. Weight loss achieved through behavioral modification or medications reduces albuminuria and in some cases slows the decline in estimated glomerular filtration rate. Use of medications that promote weight loss with favorable cardiovascular risk profiles should be promoted, particularly in patients with type 2 diabetes, obesity, and CKD. For those who fail to achieve weight loss through lifestyle modification, bariatric surgery should be considered because observational studies have shown reductions in risk for estimated glomerular filtration rate decline and kidney failure. Uncertainty persists on the risk to benefit ratio of intentional weight loss in patients with kidney failure due to the lack of prospective trials and limitations of observational data. Regardless, sleeve gastrectomy is increasingly being used for patients with kidney failure and severe obesity, with success in achieving sustained weight loss, improved access to kidney transplantation, and favorable posttransplantation outcomes. More research is needed assessing long-term cardiovascular and kidney outcomes of most weight loss medications.Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Obesity causes renal problems including albuminuria. Bariatric surgery (BS) improves albuminuria. We investigated whether albuminuria is reduced by weight loss per se or by improved systemic inflammation induced by weight loss after BS.Patients older than 18 years who received BS in Soonchunhyang University Hospital from 01 January 2011 to 31 December 2011 were included. Other inclusion criteria included body mass index (BMI) ≥ 30 kg/m, creatinine level ≤ 1.0 mg/dL, and no overt proteinuria (trace amount or undetectable by dipstick). The patients were followed at 1 and 6 months after BS.Forty-three patients were analyzed. Three patients were men, 10 patients had diabetes, and 12 patients had hypertension. All patients had normal renal function (creatinine ≤ 1.0 mg/dL), and estimated glomerular filtration rate was 115.7 ± 16.5 mL/min/1.73 m. There were significant reductions in body weight, BMI, high-sensitivity C-reactive protein (hs-CRP), and urine albumin-to-creatinine ratio (ACR). There were positive correlations between delta hs-CRP and delta body weight (r = 0.349, p = 0.043) or delta body mass index (BMI, r = 0.362, p = 0.035); between hs-CRP and body weight (r = 0.374, p = 0.001), BMI (r = 0.431, p < 0.001). Multivariate analysis using a linear mixed model demonstrated that hs-CRP (β = 0.5364, p = 0.026) was an independent risk factor affecting ACR.Our study suggests that BS can reduce albuminuria in patients with severe obesity and normal kidney function by reducing systemic inflammation.

Postoperative acute kidney injury (AKI) following bariatric surgery has not been well studied. The aim of this study is to identify factors associated with risk of AKI.The medical records of adult patients who underwent bariatric surgery between March 1, 2005 and March 31, 2011 at the Mayo Clinic were reviewed to identify patients who experienced AKI, defined as postoperative increase in serum creatinine (sCr) by 0.3 mg/dL within 72 h. For each AKI case, two controls were matched for surgical approach (laparotomy vs. laparoscopic). A chart review was conducted and conditional logistic regression analyses were performed to identify risk factors for AKI.There were 1,227 patients who underwent bariatric surgery, and of these, 71 developed AKI (5.8 %). The median sCr increase was 0.4 (interquartile range 0.3-0.6) mg/dL. Independent patient factors associated with increased risk included higher body mass index [odds ratio (OR) 1.24, 95 % CI 1.06-1.46 per 5 unit increase, P = 0.01] and medically treated diabetes mellitus (OR 2.77, 1.36-5.65, P = 0.01). Patients experiencing AKI had higher rates of blood transfusions (P < 0.01), postsurgical complications (P < 0.01), and longer hospital stays (P < 0.01). Another 30 patients developed kidney injury after 72 postoperative hours, usually in the setting of dehydration.Kidney injury following bariatric surgery is not uncommon and is associated with higher body mass index and diabetes. Further, there should be a high risk of suspicion for kidney injury in postoperative patients developing volume depletion.

The prevalence of obesity among patients with chronic kidney disease continues to increase as a reflection of the trend observed in the general population. Factors affecting the access to the waiting list and the transplantability of this specific population will be analysed. From observational studies, kidney transplantation in obese patients carries an increased risk of surgical complications compared to the nonobese population; therefore, many centres have been reluctant to proceed with transplantation, despite this treatment modality confers a survival advantage over dialysis. As a consequence, obese patients continue to face decreased access to the waiting list, with a lower likelihood of being transplanted and higher waiting times when compared to the nonobese candidates. In this review will be described the current strategies for treatment of obesity in different settings (pretransplant, at transplant and post-transplant). Obesity represents a risk factor for surgical complications but not a contraindication for kidney transplantation; outcomes could be greatly improved with its multidisciplinary and multimodal treatment. The modern technology with minimally invasive techniques, mainly using robotic platform, allows a reduction in the surgical complications rate, with graft and patient survival rates comparable to the nonobese counterpart.© 2019 Steunstichting ESOT.

The epidemiological studies indicate that the problem of obesity and associated metabolic syndrome affects the steadily increasing population. The obesity also applies to the patients with the end-stage renal failure requiring renal replacement therapy. Morbid obesity is a contraindication to renal transplantation procedure. A significant excess weight greatly increases the waiting time for transplantation, increases the risk of surgical complications, including complications due to cardiovascular and metabolic disorders. The combination of these risk factors with the immunosuppressive therapy may worsen the symptoms associated with the renal failure, contribute to the deterioration of graft function, shorten the survival, and increase the risk of patient death.In this paper we described the first Polish case of kidney transplantation, in a patient after bariatric surgery. The patient was disqualified from kidney transplantation because of obesity and referred to our department for metabolic surgery and weight reduction before potential kidney transplantation. 10 months post the bariatric surgery patient was selected as a kidney transplant recipient from a deceased donor. Both procedures have been performed in this same center.Bariatric surgery procedures are safe and effective in patients with end-stage renal disease. Bariatric procedures may be considered as a procedural bridge for a group of morbidly obese patients with renal failure, allowing them to be qualified for transplantation.

Chang et al. (2016) report a significantly lower risk of decline in estimated glomerular filtration rate among obese adults who underwent bariatric surgery compared with a matched nonsurgical cohort. In this propensity-matched analysis, data on confounding variables such as albuminuria, psychosocial, and medical conditions that precluded surgery in the comparator arm and health insurance are lacking. Furthermore, creatinine-based estimated glomerular filtration rate is not an accurate measure of kidney function after intentional weight loss. Although the study is interesting, physicians need to carefully weigh the risks versus benefits of bariatric surgery among obese adults at risk of kidney disease.Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P <.05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776).Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Gut microbiota has evolved along with their hosts and is an integral part of the human body. Microbiota acquired at birth develops in parallel as the host develops and maintains its temporal stability and diversity through adulthood until death. Recent developments in genome sequencing technologies, bioinformatics and culturomics have enabled researchers to explore the microbiota and in particular their functions at more detailed level than before. The accumulated evidences suggest that though a part of the microbiota is conserved, the dynamic members vary along the gastrointestinal tract, from infants to elderly, primitive tribes to modern societies and in different health conditions. Though the gut microbiota is dynamic, it performs some basic functions in the immunological, metabolic, structural and neurological landscapes of the human body. Gut microbiota also exerts significant influence on both physical and mental health of an individual. An in-depth understanding of the functioning of gut microbiota has led to some very exciting developments in therapeutics, such as prebiotics, probiotics, drugs and faecal transplantation leading to improved health.

The history of fecal microbiota transplantation (FMT) dates back even to ancient China. Recently, scientific studies have been looking into FMT as a promising treatment of various diseases, while in the process teaching us about the interaction between the human host and its resident microbial communities. Current research focuses mainly on Clostridium difficile infections, however interest is rising in other areas such as inflammatory bowel disease (IBD) and the metabolic syndrome. With regard to the latter, the intestinal microbiota might be causally related to the progression of insulin resistance and diabetes. FMT in metabolic syndrome has proven to be an intriguing method to study the role of the gut microbiota and open the way to new therapies by dissecting in whom insulin resistance is driven by microbiota. In this article we review the history of FMT, the present evidence on its role in the pathophysiology of metabolic syndrome and its efficacy, limitations and future prospects.

Targeting gut microbiota has shown promise to prevent experimental acute kidney injury (AKI). However, this has not been studied in relation to accelerating recovery and preventing fibrosis. Here, we found that modifying gut microbiota with an antibiotic administered after severe ischemic kidney injury in mice, particularly with amoxicillin, accelerated recovery. These indices of recovery included increased glomerular filtration rate, diminution of kidney fibrosis, and reduction of kidney profibrotic gene expression. Amoxicillin was found to increase stool Alistipes, Odoribacter and Stomatobaculum species while significantly depleting Holdemanella and Anaeroplasma. Specifically, amoxicillin treatment reduced kidney CD4T cells, interleukin (IL)-17 CD4T cells, and tumor necrosis factor-α double negative T cells while it increased CD8T cells and PD1CD8T cells. Amoxicillin also increased gut lamina propria CD4T cells while decreasing CD8T and IL-17CD4T cells. Amoxicillin did not accelerate repair in germ-free or CD8-deficient mice, demonstrating microbiome and CD8T lymphocytes dependence for amoxicillin protective effects. However, amoxicillin remained effective in CD4-deficient mice. Fecal microbiota transplantation from amoxicillin-treated to germ-free mice reduced kidney fibrosis and increased Foxp3CD8T cells. Amoxicillin pre-treatment protected mice against kidney bilateral ischemia reperfusion injury but not cisplatin-induced AKI. Thus, modification of gut bacteria with amoxicillin after severe ischemic AKI is a promising novel therapeutic approach to accelerate recovery of kidney function and mitigate the progression of AKI to chronic kidney disease.Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.