The metabolic syndrome and chronic kidney disease

PURPOSE OF REVIEW: The metabolic syndrome is a constellation of physical and laboratory abnormalities including hypertension, hyperglycemia, hyperlipidemia and abdominal obesity. Over the past decade, the metabolic syndrome has emerged as a critically important risk factor for cardiovascular disease. RECENT FINDINGS: A large population-based cross-sectional analysis (the National Health and Nutrition Evaluation Survey III) found that the presence of the metabolic syndrome was associated with chronic kidney disease, defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m and was also associated with proteinuria. More recently, a prospective cohort study found that the presence of the metabolic syndrome was associated with incident chronic kidney disease by the same definition, even when excluding individuals with diabetes mellitus and hypertension. More studies are required to determine whether the relationship between the metabolic syndrome and chronic kidney disease is mainly mediated by hyperglycemia (with insulin resistance) and hypertension, or other metabolic or hemodynamic factors. SUMMARY: The metabolic syndrome is associated with chronic kidney disease. Efforts aimed at determining the mechanisms underlying this association and strategies for the prevention of chronic kidney disease (or slowing the progression of chronic kidney disease) in affected patients should be research priorities in the future.     

Impact of metabolic syndrome on the incidence of chronic kidney disease: a Chinese cohort study

Aim: Metabolic syndrome (MetS) is a major culprit in cardiovascular disease and chronic kidney disease (CKD) in Western populations. We studied the longitudinal association between MetS and incident CKD in Chinese adults. Methods: A cohort study was conducted in a nationally representative sample of 4248 Chinese adults in Taiwan. The MetS was defined according to a unified criteria set by several major organizations and CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m². Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for sex, age, body mass index (BMI) and serum levels of total cholesterol. Results: The prevalence of MetS among participants at baseline recruitment was 15.0% (637/4248). During a median follow‐up period of 5.40 years, 208 subjects (4.9%) developed CKD. The multivariate‐adjusted HR of CKD in participants with MetS compared with those without was 1.42 (95% CI = 1.03, 1.73). Additionally, there was a significantly graded relationship between the number of the MetS components and risk of CKD. Further, the relation between MetS and incident CKD was more robust in subjects with BMI >27.5 kg/m² than in those with lower BMI. Conclusion: The results suggest that the presence of MetS was significantly associated with increased risk of incident CKD in a Chinese population. These findings warrant future studies to test the impact of preventing and treating MetS on the reduction of the occurrence of CKD.     

Relationship between serum uric acid levels with chronic kidney disease in a Southeast Asian population

Aim: Elevated serum uric level has been suggested as a risk factor for chronic kidney disease (CKD). The relationship between serum uric acid level, and CKD in a Southeast Asian population was examined. Methods: In a cross‐sectional study, authors surveyed 5618 subjects, but 5546 participants were included. The glomerular filtration rate (GFR) values were calculated by the Modification of Diet in Renal Disease (MDRD) equation. CKD was defined as a GFR of less than 60 mL/min per 1.73 m². Multivariate binary logistic regression was used to determine the association between serum uric acid level and CKD. Results: The prevalence of CKD in serum uric acid quartiles: first quartile, 5.3 mg/dL or less; second quartile, 5.4–6.4 mg/dL; third quartile, 6.5–7.6 mg/dL; and fourth quartile, 7.7 mg/dL or more were 1.8%, 3.6%, 5.5% and 11.9%, respectively (P < 0.001). The mean values of estimated GFR in participants with CKD and without CKD were 53.44 ± 7.72 and 81.26 ± 12.48 mL/min per 1.73 m² respectively. In the entire participants, there were 6.76% with hypertension and 2.64% with diabetes as a comorbid disease. Compared with serum uric acid first quartile, the multivariate‐adjusted odds for CKD of the fourth, third and second quartile were 10.94 (95% confidence interval (CI), 6.62–16.08), 4.17 (95% CI, 2.51–6.92) and 2.38 (95% CI, 1.43–3.95), respectively. Conclusion: High serum uric acid level was independently associated with increased prevalence of CKD in the Southeast Asian population. Detection and treatment of hyperuricaemia should be attended as a strategy to prevent CKD.     

Prevalence of chronic kidney disease in adults with metabolic syndrome

The burden of chronic kidney disease (CKD) and other non- communicable diseases continues to rise globally, and recent studies suggest that metabolic syndrome (MS) may add to this burden by contributing to the development of CKD. Given that reports on the prevalence of CKD in patients with MS in this environment are scanty, this study was undertaken with the sole aim of determining the prevalence of CKD in subjects with MS as defined by the International Diabetes Federation (IDF) and the National Cholesterol Education Project Adult Treatment Panel III (NCEP ATP III). A total of 240 consenting adults (18-70 years) attending the general out- patient clinic of the General Hospital Okrika for various ailments were studied. Subjects were screened for MS as per the above- mentioned criteria. Estimated GFR (eGFR) was determined with Modification of Diet for Renal Disease (MDRD) formula and CKD was defined as eGFR less than 60 mL/min/1.73 m2 . Data was analyzed using SPSS version 12.0 and Epi info version 4.06d; P <0.05 was considered as significant. A total of 88 males and 152 females were screened for MS by both criteria. Eighty- four (35.0%) of 240 subjects had MS as defined by NCEP ATP III, while 85 (35.4%) had MS as defined by the IDF. The subjects were predominantly females, and mean age was between 54.74 ± 15.30 and 55.60 ± 14.81 years. Four of the 84 (4.8%) subjects with MS by NCEP ATP III definition had CKD while three of the 85 (3.5%) subjects with MS by IDF definition had CKD. Among subjects without MS by either definition, the prevalence of CKD was four of 140 (2.9%). Although the prevalence of CKD was higher among subjects with MS by ATP III compared with those with MS as defined by IDF and subjects without MS, the differences were not statistically significant (X2 = 0.14; P = 0.710). A comparison of MS subjects without CKD and those with CKD did not show any significant difference in age, waist circumference, body mass index, blood pressure, fasting blood glucose and lipid profile (P > 0.05). CKD was more common in subjects with MS compared with those without, although the difference was not statistically significant. The prevalence of CKD in subjects with MS in our study population did not differ significantly when the different MS definitions were employed.     

Association between metabolic syndrome and chronic kidney disease in the Korean population

Aim:   We performed a retrospective study to examine the association between the metabolic syndrome (MS) and risk for the development of chronic kidney disease (CKD).
Methods:   This cohort study included 60 921 healthy adults recruited from two health promotion centres. Anthropometric measures, blood pressure, fasting glucose, lipid profile and serum creatinine were evaluated. The glomerular filtration rate was estimated (eGFR) using the abbreviated equation developed by the Modification of Diet in Renal Disease (MDRD) formula. CKD was defined as an eGFR of <60 mL/min per 1.73 m² or the presence of proteinuria.
Results:   The prevalence of MS and CKD was 19.0% and 7.2% respectively. Those with MS had a higher prevalence of CKD (11.0% vs 6.3%, P  < 0.001) than those without MS. As the number of MS components increased, the prevalence of CKD increased and the eGFR decreased. The multiple linear analyses showed that each of the components of the MS was negatively correlated with the eGFR. Unadjusted and multivariate adjusted associations were identified between MS and CKD. Individuals with MS had a multivariate adjusted odds ratio of 1.680 (95% confidence interval, 0.566–1.801) for CKD compared with those without MS.
Conclusion:   Our findings, which were obtained from a large Korean cohort, suggest that MS was associated with CKD.     

Association between the metabolic syndrome and chronic kidney disease in Chinese adults.

BACKGROUND: The metabolic syndrome is a common risk factor for cardiovascular and chronic kidney disease (CKD) in Western populations. We examined the relationship between the metabolic syndrome and risk of CKD in Chinese adults. METHODS: A cross-sectional survey was conducted in a nationally representative sample of 15 160 Chinese adults aged 35-74 years. The metabolic syndrome was defined as the presence of three or more of the following risk factors: elevated blood pressure, low high density lipoprotein (HDL)-cholesterol, high triglycerides, elevated plasma glucose and abdominal obesity. CKD was defined as an estimated glomerular filtration rate<60 ml/min/1.73 m2 and elevated serum creatinine was defined as >or=1.14 mg/dl in men and >or=0.97 mg/dl in women (>or=95th percentile of serum creatinine in Chinese men and women aged 35-44 years without hypertension or diabetes, respectively). RESULTS: The multivariate-adjusted odds ratios [95% confidence interval (CI)] of CKD and elevated serum creatinine in participants with compared to those without the metabolic syndrome were 1.64 (1.16, 2.32) and 1.36 (1.07, 1.73), respectively. Compared to participants without any components of the metabolic syndrome, the multivariate-adjusted odds ratios (95% CI) of CKD were 1.51 (1.02, 2.23), 1.50 (0.97, 2.32), 2.13 (1.30, 3.50) and 2.72 (1.50, 4.93) for those with 1, 2, 3, and 4 or 5 components, respectively. The corresponding multivariate-adjusted odds ratios (95% CI) of elevated serum creatinine were 1.11 (0.88, 1.40), 1.39 (1.07, 2.04), 1.47 (1.06, 2.04) and 2.00 (1.32, 3.03), respectively. CONCLUSIONS: These findings suggest that the metabolic syndrome might be an important risk factor for CKD in Chinese adults.     

代谢综合征及其代谢因子与慢性肾损害相关性的临床研究

目的 探讨代谢综合征及其各组成因子与包括轻度肾损害在内的慢性肾损害的相关性&#65377; 方法 收集我院2003年1月至2003年12月心内科&#65380; 肾内科和内分泌科符合入选标准的住院患者966例进行回顾性分析&#65377;按有&#65380; 无慢性肾脏病(CKD)或轻度肾损害分组, 比较代谢综合征各因素与慢性肾脏损害的关系&#65377; 统计学处理包括单变量t检验&#65380;卡方检验和Logistic多因素回归分析&#65377;结果 (1)CKD组的年龄&#65380; 身体质量指数(BMI)&#65380; 总胆固醇(TC)&#65380; 甘油三酯(TG)&#65380; 高血糖&#65380; 高血压和尿酸水平, 冠心病&#65380; 脑卒中的患病率均高于无CKD组, 而高密度脂蛋白(HDL)水平明显低于无CKD组患者; (2)随着代谢综合征因子数量的增多, CKD发病率上升; (3)代谢综合征中各因子并存较各因子单独存在的CKD的危险性增加, 与高血糖并存的频率最高; (4)BMI增加也是CKD的重要危险因素; (5)高血糖患者发生轻度肾损害的风险最大(优势比OR=7.698)&#65377;结论 代谢综合征及其各组成因子是包括轻度肾损害在内的CKD的重要危险因素&#65377;随着代谢综合征因子的增多, CKD的危险也随之增加&#65377; 除了高血糖和高血压, BMI增加也是其中重要的影响因子&#65377;     

Activation of the aldosterone/mineralocorticoid receptor system in chronic kidney disease and metabolic syndrome

Recent clinical and experimental studies have shown that aldosterone is a potent inducer of proteinuria and that mineralocorticoid receptor (MR) antagonists confer efficient antiproteinuric effects. We identified glomerular epithelial cells (podocytes) as novel targets of aldosterone; activation of MR injures podocytes possibly via oxidative stress, resulting in disruption of glomerular filtration barrier, proteinuria, and progression of chronic kidney disease. We also demonstrated that SHR/cp, a rat model of metabolic syndrome, was susceptible to podocyte injury and proteinuria. Aldosterone excess caused by adipocyte-derived aldosterone-releasing factors was suggested to underlie the nephropathy. High salt intake augmented MR activation in the kidney and exacerbated the nephropathy. Furthermore, we identified an alternative pathway of MR activation by small GTPase Rac1. RhoGDIα knockout mice, a model with Rac1 activation in the kidney, showed albuminuria, podocyte injury, and glomerulosclerosis. Renal injury in the knockout mice was accompanied by enhanced MR signaling in the kidney despite normoaldosteronemia, and was ameliorated by an MR antagonist, eplerenone. Moreover, Rac-specific inhibitor significantly reduced the nephropathy, concomitantly with repression of MR activation. In vitro transfection studies provided direct evidence of Rac1-mediated MR activation. In conclusion, our findings suggest that MR activation plays a pivotal role in the pathogenesis of chronic kidney disease in metabolic syndrome, and that MR may be activated both aldosterone dependently (via aldosterone-releasing factors) and independently (via Rac1). MR antagonists are promising antiproteinuric drugs in metabolic syndrome, although long-term effects on renal outcomes, mortality, and safety need to be established.     

Pseudoexfoliation syndrome in chronic kidney disease patients

Abstract

This study was performed to determine whether chronic kidney disease (CKD) is associated with an increased risk of pseudoexfoliation (PEX) syndrome. This is an age-matched case control study evaluating frequency of PEX in patients over age 40 with the diagnosis of stage 1–4 CKD and those undergoing hemodialysis (HD). Subjects over age 40 with hypertension and/or diabetes mellitus (DM) and normal kidney functions were studied as a control group. CKD was diagnosed as decreased glomerular filtration rate (GFR) of less than 60?mL/min/1.73?m² for at least 3 months. Study groups were arranged as group 1 consisting of HD receiving CKD patients, group 2 consisting of CKD patients who do not need HD and group 3 as a control. Demographic properties and the prevalence of PEX were evaluated and compared between groups. Because of the effect of DM on PEX occurrence, it was also evaluated after exclusion of diabetic patients. A total of 101 cases in group 1, 106 cases in group 2 and 117 cases in group 3 were included in the study. Pseudoexfoliation was found in 7 (6.9%) patients in group 1, 5 (4.7%) patients in group 2 and 7 (5.9%) patients in group 3 (p?>?0.05). After exclusion of diabetic patients the prevalence of PEX changed as 4 (5.6%) in group 1, 2 (4.4%) in group 2 and 1 (1.8%) in group 3 (p?>?0.05). In conclusion, CKD was not associated with increased prevalence of PEX in this study.     

队列研究在慢性肾脏病流行病学研究中的重要性

近10余年来,慢性肾脏病(CKD)的流行病学研究成为肾脏病领域的热点.在这一趋势的带动下,我国各个地区陆续开展了若干关于CKD患病率的横断面研究,为评估我国CKD患病现状提供了大量数据.来自北京、上海、广州3个大城市的研究显示成年人群中CKD患病率为11.8%～13.0%[1-3],与美国的水平接近.CKD的相关因素包括传统危险因素,如高血压、糖尿病、老年等,此外还有具中国特色的危险因素,如肾毒性药物等.时至今日,在此领域国际上已经鲜见针对患病率的横断面研究,取而代之的是各种队列研究提供的关于CKD危险因素、疾病进展、并发症发生等的诸多证据.我们介绍队列研究这一流行病学研究的经典方法,并阐述开展队列研究的注意事项.     

Risks of chronic metabolic acidosis in patients with chronic kidney disease

Risks of chronic metabolic acidosis in patients with chronic kidney disease. Metabolic acidosis is associated with chronic renal failure (CRF). Often, maintenance dialysis therapies are not able to reverse this condition. The major systemic consequences of chronic metabolic acidosis are increased protein catabolism, decreased protein synthesis, and a negative protein balance that improves after bicarbonate supplementation. Metabolic acidosis also induces insulin resistance and a decrease in the elevated serum leptin levels associated with CRF. These three factors may promote protein catabolism in maintenance dialysis patients. Available data suggest that metabolic acidosis is both catabolic and anti-anabolic. Several clinical studies have shown that correction of metabolic acidosis in maintenance dialysis patients is associated with modest improvements in nutritional status. Preliminary evidence indicates that metabolic acidosis may play a role in beta2-microglobulin accumulation, as well as the hypertriglyceridemia seen in renal failure. Interventional studies for metabolic acidosis have yielded inconsistent results in CRF and maintenance hemodialysis patients. In chronic peritoneal dialysis patients, the mitigation of acidemia appears more consistently to improve nutritional status and reduce hospitalizations. Large-scale, prospective, randomized interventional studies are needed to ascertain the potential benefits of correcting acidemia in maintenance hemodialysis patients. To avoid adverse events, an aggressive management approach is necessary to correct metabolic acidosis. Clinicians should attempt to adhere to the National Kidney Foundation Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines for maintenance dialysis patients. The guidelines recommend maintenance of serum bicarbonate levels at 22 mEq/L or greater.     

Uremia-related metabolic cardiac risk factors in chronic kidney disease

Growing evidence has been gathered over the last 15 years regarding the role of nontraditional or uremia-related risk factors in the pathogenesis of atherosclerosis in subjects with renal failure. Among those factors, dyslipidemia, inflammation, hyperhomocysteinemia, and oxidant stress have been extensively studied. However, the clinical significance of many of these factors remains controversial in light of reported studies. In this article, the existing evidence regarding the role of uremia-related risk factors in the pathogenesis of atherosclerosis is reviewed, with special emphasis on prevalence, cardiac risk, and management in patients with chronic kidney disease (CKD). Consensus treatment recommendations are provided for risk factors for which there is evidence to support preventive or therapeutic interventions.     

Transition from acute kidney injury to chronic kidney disease: a single-centre cohort study

Background

The incidence of acute kidney injury (AKI) is increasing. AKI is currently recognised as an inducer of chronic kidney disease (CKD) and this is known as the ‘AKI–CKD transition’. This study aimed to evaluate the rate of decline in estimated glomerular filtration rate (eGFR) associated with AKI events in individuals with and without pre-existing CKD.

Methods

Inpatients aged 18–80 years were retrospectively enrolled. AKI was diagnosed according to the kidney disease improving global outcomes (KDIGO) criteria using serum creatinine levels. Patients with a history of AKI events were divided into four groups according to eGFR before and after the AKI events. In each group, the eGFR levels after an AKI event were compared to those before the AKI event. Patients were further divided into eight groups according to clinical background based on underlying diseases, medications, and surgical history.

Results

We analysed data from 9651 patients with AKI. Not surprisingly, we found that eGFR levels during the first AKI event were significantly lower than levels before the event in each group. Furthermore, eGFR levels after the first AKI event were significantly lower than those before the first AKI event, and the eGFR levels after the second AKI event were significantly lower than those after the first AKI event. These trends were similar in each group irrespective of clinical background.

Conclusions

Our study revealed that AKI events can cause a decline in kidney function and, as more AKI events occur, acceleration of this decline.

     

A polygenic score for reduced kidney function and adverse outcomes in a cohort with chronic kidney disease

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The impact of inflammation on metabolic regulation in chronic kidney disease: a review.

Chronically uremic patients are characterized by a low-grade systemic inflammation that reflects the consequences of an unbalanced production of proinflammatory and anti-inflammatory cytokines and contributes to the progression of atherosclerotic vascular disease and malnutrition. The causes of inflammation in end-stage kidney disease have been studied in details. Nonetheless, the degree of activation of the systemic inflammatory response shows great interindividual variability that cannot be explained by renal disease or dialysis. The amount of cytokine that is produced on a definite stimulus varies among individuals. Single nucleotide polymorphisms in the promoter or coding regions of cytokine genes lead to high or low productions of these mediators and may genetically explain this heterogeneity. The "low-producer" genotypes for the anti-inflammatory cytokine interleukin-10 are more permissive for a greater level of systemic inflammation and for increased cardiovascular morbidity and mortality in patients on hemodialysis. Potential pharmacologic and nutritional approaches for treatment of systemic inflammation have been identified in recent years. In addition, physical exercise training may reduce the systemic inflammatory response. Definition of the relationships between different cytokine gene polymorphisms and systemic inflammation in chronically uremic patients will improve efficacy of targeted anti-inflammatory treatments.     

Prognosis and risk factors of chronic kidney disease progression in patients with diabetic kidney disease and non-diabetic kidney disease: a prospective cohort CKD-ROUTE study

Diabetic kidney disease (DKD) is emerging rapidly as the leading cause of chronic kidney disease (CKD) worldwide. In this 3-year prospective, multicenter cohort study, a total of 1138 pre-dialysis CKD patients were recruited. Patients were categorized into two groups according to the etiologies of DKD and non-diabetic kidney disease (NDKD). Propensity score matching was performed to adjust for confounding factors, resulting in 197 patients being assigned to DKD and NDKD groups, respectively. The primary endpoints were 50% estimated glomerular filtration rate (eGFR) decline and initiation of kidney replacement therapy (KRT). The secondary endpoints were all-cause death and the development of cardiovascular disease (CVD) events. We found that DKD patients have a higher risk to develop 50% eGFR decline endpoint (HR:2.30, 95%CI [1.48–3.58], p < 0.001) and KRT endpoint (HR:1.64, 95%CI [1.13–2.37], p < 0.05) than NDKD patients. The 3-year cumulative incidence of 50% eGFR decline and KRT endpoint was significantly higher in DKD patients (26.90% vs.13.71% and 35.03% vs. 22.34%, respectively). The Cox regression analyses showed that the increased systolic blood pressure (SBP), DKD, decreased serum albumin (Alb), and higher CKD stages were risk factors for the 50% eGFR decline endpoint; the increased SBP, DKD, decreased serum Alb, serum creatinine (Scr), higher CKD stages, presence of proteinuria and CVD were risk factors for KRT endpoint; the increased age, decreased hemoglobin (Hb), decreased serum Alb were risk factors for all-cause death endpoint; the increased age, decreased serum Alb were risk factors for CVD events endpoint. Appropriate preventive or therapeutic interventions should be taken to control these predictive factors to delay the development of CKD complications, thereby improving the prognosis and reducing the disease burden of the high-risk populations.