Factors influencing the development of end-stage renal disease

Epidemiological evidence is needed to design effective strategies for preventing chronic kidney disease (CKD) and end-stage renal disease (ESRD). Several types of health check are routinely performed in Japan, including the screening of asymptomatic individuals, but the potential benefits of these procedures remain unknown. We evaluated the predictors of ESRD, using community-based mass screening and a dialysis registry. This approach revealed the significance of proteinuria, hypertension, obesity, anemia, and high fasting plasma glucose levels (which indicate diabetes mellitus; DM), for the risk of developing ESRD. Lifestyle-related factors, such as smoking, alcohol consumption, and low levels of exercise, are also associated with these conditions and, in particular, with a high risk of ESRD. Over-nutrition and low levels of exercise can ultimately lead to DM, hypertension, hyperlipidemia, and obesity, and are important risk factors worldwide for cardiovascular diseases, CKD, and ESRD. The early detection and treatment of predictors of ESRD, along with appropriate treatment for CKD, may decrease the incidence of ESRD. In addition, the economic burden caused by the costs of dialysis presents a compelling argument for implementing a cost-effective preventive strategy against ESRD.     

Weight gain after kidney donation: Association with increased risks of type 2 diabetes and hypertension

In the general population, obesity is associated with an increased risk of developing hypertension (HTN), type 2 diabetes mellitus (DM), and end‐stage renal disease (ESRD). Therefore, most transplant centers have a body mass index (BMI) threshold for accepting living kidney donors. But there have been no studies of postdonation weight gain trends and any associated risks. We tracked serial BMIs in 940 donors for a median (IQ range) follow‐up of 22.3 (15.4‐35.8) years. We studied the impact of postdonation weight gain in a model adjusted for family history of HTN or DM. Donor characteristics included age, sex, smoking, fasting blood glucose, eGFR, systolic and diastolic BP, and BMI at time of donation and time postdonation. Postdonation weight gain was associated with a significant increase in the relative risk of developing HTN RR 1.93 (95% CI 1.51‐2.46) (P < 0.001) and/or DM RR 4.18 (95% CI 2.05‐8.5) (P < 0.0001), but not (to date) cardiovascular disease (CVD), reduced eGFR or death. Like the general population, donors gained weight as they aged; a higher BMI was associated with higher incidence of DM and HTN. Postdonation care should include ongoing counseling on the risks of substantial weight gain.     

Meta-analysis of the relationship between ACE I/D gene polymorphism and end-stage renal disease in patients with diabetic nephropathy

Aims: Diabetic nephropathy (DN) is the major cause for end‐stage renal disease (ESRD) and the pathogenesis for DN developing into ESRD is not clear at present. Results from published studies on the relationship between angiotensin‐converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and ESRD risk in DN patients are still conflicting. This meta‐analysis was performed to evaluate the association between ACE I/D gene polymorphism and ESRD risk in DN patients. Methods: Association studies were identified from the databases of PubMed, Embase and Cochrane Library on 1 October 2011, and eligible investigations were identified and synthesized using the meta‐analysis method. Results were expressed using odds ratios (OR) for dichotomous data and 95% confidence intervals (CI) were also calculated. Results: Twelve studies reporting the relation between ACE I/D gene polymorphism and ESRD risk in DN patients were identified. In overall populations, there was a notable association between D allele or DD genotype and ESRD susceptibility (D: OR = 1.32, 95% CI: 1.11–1.56, P = 0.002; DD: OR = 1.67, 95% CI: 1.25–2.21, P = 0.0004). In the sub‐group analysis according to ethnicity, D allele or DD genotype was associated with ESRD risk in Asians. In Caucasians, the association of DD genotype with ESRD risk was observed, but the D allele was not. Furthermore, ACE I/D gene polymorphism was associated with ESRD risk in patients with DN due to diabetes mellitus type 2, but the association was not found for patients with DN due to diabetes mellitus type‐1. Conclusions: Our results indicate that D allele or DD homozygous is associated with the ESRD susceptibility in DN patients. However, more investigations are required to further this association.     

Renal Consequences of Diabetes After Kidney Donation

Whether diabetes after kidney donation is associated with an accelerated GFR decay in the remaining kidney has not been studied. We determined the incidence of diabetes in kidney donors, and compared GFR change over time in diabetic to nondiabetic donors, in addition to the effect of diabetes mellitus (DM) on the development of proteinuria, hypertension, and end‐stage renal disease (ESRD). Of the 4014 donors, 309 (7.7%) developed diabetes at a median age of 56.0 years and after a median of 18 years after donation. The difference in annual estimated GFR (eGFR) change between diabetic and nondiabetic donors in the 7 years before the development of DM was ?0.08 mL/min/year; p = 0.51. After DM development, the difference was ?1.10 mL/min/year for diabetic donors with hypertension and proteinuria, p < 0.001; ?0.19 for diabetic donors with hypertension but no proteinuria, p = 0.29; ?0.75 mL/min/year for diabetic donors with proteinuria but no hypertension, p = 0.19; and ?0.09 mL/min/year for diabetic donors without proteinuria or hypertension, p = 0.63. When DM was considered as a time‐dependent covariate, it was associated with the development of proteinuria (hazard ratio [HR] 2.65, 95% confidence interval [CI] 1.89–3.70; p < 0.001) and hypertension (HR 2.19, 95% CI 1.74–2.75; p < 0.001). It was not, however, associated with ESRD. eGFR decline after DM development exceeds that of nondiabetic donors only in diabetic donors with concomitant proteinuria and hypertension.     

Risk factor profiles based on estimated glomerular filtration rate and dipstick proteinuria among participants of the Specific Health Check and Guidance System in Japan 2008

Background

Estimated glomerular filtration rate (eGFR) and albuminuria (proteinuria) are both important determinants of the risk of cardiovascular disease (CVD), end-stage renal disease (ESRD), and mortality. Few studies, however, have examined the risk factor profiles based on eGFR and proteinuria among the general population.

Methods

Data of the newly developed nationwide screening program of the Specific Health Check-up and Guidance System (Tokutei-Kensin) initiated in 2008 were used in this study. The aim of this screening, targeting people 40?C74?years of age, was to detect those with metabolic syndrome and to offer those services regarding lifestyle modifications that will lead to the reduction of diabetes mellitus (DM) and DM-related ESRD. Individual records of 580,000 participants in 69 cities and towns and 3 union cohorts throughout Japan were anonymously provided and included in the present study.

Results

Details of 332,174 participants (57.3% of the total) with both serum creatinine and dipstick urine test data were analyzed. Mean (SD) age was 63.6 (8.3) years and 40.6% were men. The mean (SD) eGFR was 75.0 (16.2) ml/min/1.73?m² and 5.4% had proteinuria. The prevalence of chronic kidney disease (CKD) stage 3, 4, and 5 was 14.2%, 0.2%, and 0.07%, respectively. The prevalence of DM, hypertension, and history of stroke and heart disease was correlated with the combination of eGFR and degree of proteinuria.

Conclusion

The findings of the present study indicate that CKD and risk factors for CVD are quite common among middle-aged Japanese. CKD classification based on eGFR and proteinuria may be useful for predicting CVD, mortality rate, and ESRD in the Japanese population.     

Sodium intake, ACE inhibition, and progression to ESRD

High sodium intake limits the antihypertensive and antiproteinuric effects of angiotensin-converting enzyme (ACE) inhibitors in patients with CKD; however, whether dietary sodium also associates with progression to ESRD is unknown. We conducted a post hoc analysis of the first and second Ramipril Efficacy in Nephropathy trials to evaluate the association of sodium intake with proteinuria and progression to ESRD among 500 CKD patients without diabetes who were treated with ramipril (5 mg/d) and monitored with serial 24-hour urinary sodium and creatinine measurements. Urinary sodium/creatinine excretion defined low (<100 mEq/g), medium (100 to <200 mEq/g), and high (≥200 mEq/g) sodium intake. During a follow-up of >4.25 years, 92 individuals (18.4%) developed ESRD. Among those with low, medium, and high sodium intakes, the incidence of ESRD was 6.1 (95% confidence interval [95% CI], 3.8-9.7), 7.9 (95% CI, 6.1-10.2), and 18.2 (95% CI, 11.3-29.3) per 100 patient-years, respectively (P<0.001). Patients with high dietary sodium exhibited a blunted antiproteinuric effect of ACE inhibition despite similar BP among groups. Each 100-mEq/g increase in urinary sodium/creatinine excretion associated with a 1.61-fold (95% CI, 1.15-2.24) higher risk for ESRD; adjusting for baseline proteinuria attenuated this association to 1.38-fold (95% CI, 0.95-2.00). This association was independent from BP but was lost after adjusting for changes in proteinuria. In summary, among patients with CKD but without diabetes, high dietary salt (>14 g daily) seems to blunt the antiproteinuric effect of ACE inhibitor therapy and increase the risk for ESRD, independent of BP control.     

The conundrum of increased burden of end-stage renal disease in Asians

BACKGROUND: Few cohort studies have examined the risk of end-stage renal disease (ESRD) among Asians compared with whites and blacks. METHODS: To compare the incidence of ESRD in Asians, whites, and blacks in Northern California, we examined sociodemographic and clinical data on 299,168 adults who underwent a screening health checkup at Kaiser Permanente between 1964 and 1985. Incident cases of ESRD were ascertained by matching patient identifiers with the nationally comprehensive United States Renal Data System ESRD registry. RESULTS: Overall, 1346 cases of ESRD occurred during 7,837,310 person-years of follow-up. The age-adjusted rate of ESRD (per 100,000 person-years) was 14.0 [95% confidence interval (CI) 10.5-18.5] among Asians, 7.9 (95% CI 6.5-9.5) among whites, and 43.4 (95% CI 36.6-51.4)] among blacks. Controlling for age, gender, educational attainment, diabetes, prior myocardial infarction, serum creatinine, systolic and diastolic blood pressure, proteinuria, hematuria, cigarette smoking, serum total cholesterol, and body mass index increased the risk of ESRD in Asians relative to whites from 1.69 to 2.08 (95% CI 1.61-2.67). By contrast, adjustment for the same covariates decreased the risk of ESRD in blacks relative to whites from 5.30 to 3.28 (95% CI 2.91-3.69). CONCLUSION: Factors contributing to the excess ESRD risk in Asians relative to whites extend beyond usually considered sociodemographic and comorbidity disparities. Strategies aimed at examining novel risk factors for kidney disease and efforts to increase awareness of kidney disease among Asians may reduce ESRD incidence in this high-risk group.     

Decreased body mass index as an independent risk factor for developing chronic kidney disease

BACKGROUND: Obesity and metabolic syndrome are risk factors for the development of chronic kidney disease (CKD). Few studies have examined the effect of change in body mass index (DeltaBMI) on CKD incidence in a general screening setting. METHODS: Subjects of this study were screenees that participated in the screening program of the Okinawa General Health Maintenance Association in 1993 and 2003 in Okinawa, Japan. Using identification number, birth date, sex, and other recorded identifiers, we identified 33,389 subjects among the 1993 screening participants (N = 143,948) who also participated in the 2003 screening. CKD was defined as estimated glomerular filtration rate <60 ml/min/1.73 m(2), according to the modification of diet in renal disease study equation. Obesity was defined as BMI > or = 25 kg/m(2). RESULTS: CKD prevalence was 13.8% in 1993 and 22.4% in 2003. The incidence of developing CKD in 10 years was 15.5%. The effect of DeltaBMI on CKD incidence was evaluated after considering other confounding factors such as age, sex, blood pressure, BMI, fasting plasma glucose, and proteinuria. Median DeltaBMI was 1.0%. The adjusted odds ratio (95% CI) for the effect of DeltaBMI on CKD incidence was 1.111 (1.026-1.204, P < 0.01; entire study population), 1.271 (1.116-1.448, P = 0.0030; men), and 1.030 (0.931-1.139, NS; women), when DeltaBMI > or = 1% was taken as a reference. DeltaBMI was an independent predictor of CKD incidence. CONCLUSIONS: The present results suggest that there was an inverse relationship between DeltaBMI and CKD incidence among screened subjects. The reasons for this observation are not clear, but careful follow-up for DeltaBMI is necessary, particularly in obese men with proteinuria.     

Prevalence of high fasting plasma glucose and risk of developing end-stage renal disease in screened subjects in Okinawa,Japan

Background The number of diabetic dialysis patients is increasing worldwide. Only a few studies, however, have examined the effect of diabetes mellitus (DM) as a risk factor for the development of end-stage renal disease (ESRD) in the general population.Methods We examined the cumulative incidence of ESRD based on the results of community-based mass screening in Okinawa, Japan, performed in 1993 by the Okinawa General Health Maintenance Association. Fasting plasma glucose (FPG) data were available for 78529 screenees (37197 men and 41332 women). DM was diagnosed when the FPG was 126mg/dl or more. Screenees who developed ESRD by the end of 2000 were identified through the Dialysis Registry, Okinawa Dialysis Study.Results The mean (SD) FPG was 96.5 (22.8)mg/dl, ranging from 45 to 577mg/dl. The prevalence of DM among the screenees was 4089 (5.2%). A total of 133 screenees (82 men and 51 women) developed ESRD during the 7.75-year study period. The adjusted odds ratio (95% confidence interval [CI]) in the high-FPG group for the risk of developing ESRD was 3.098 (95% CI, 1.738–5.525; P = 0.0001), when adjusted for age, sex, systolic blood pressure, diastolic blood pressure, body mass index, total cholesterol, triglyceride, hematocrit, serum creatinine, hematuria, and proteinuria.Conclusions The results of the present study indicated that FPG is a significant, independent predictor of ESRD. FPG and proteinuria measurements are euqally important in detecting individuals at high risk for developing ESRD.     

Proteinuria and the risk of developing end-stage renal disease

BACKGROUND: Dipstick urinalysis for proteinuria and hematuria has been used to screen renal disease, but evidence of the clinical impact of this test on development of end-stage renal disease (ESRD) is lacking. METHODS: We assessed development of ESRD through 2000 in 106,177 screened patients (50,584 men and 55,593 women), 20 to 98 years old, in Okinawa, Japan, who participated in community-based mass screening between April 1983 and March 1984. We used data from the Okinawa Dialysis Study Registry to identify ESRD patients. Multivariate logistic analyses were performed to calculate adjusted odds ratio and 95% confidence interval (95% CI) for the significance of proteinuria and hematuria on the risk of developing ESRD with confounding variables such as age, gender, blood pressure, and body mass index. A similar analysis was repeated in a subgroup of screened patients in whom serum creatinine data existed. RESULTS: During 17 years of follow-up, 420 screened persons (246 men and 174 women) entered the ESRD program. We identified a strong, graded relationship between ESRD and dipstick urinalysis positive for proteinuria; adjusted odds ratio (95% CI) was 2.71 (2.51 to 2.92, P < 0.001). Similar trends were observed after adding serum creatinine data. Compared with dipstick-negative proteinuria, adjusted odds ratio (95% CI) of proteinuria (1+) was 1.93 (1.53 to 2.41, P < 0.001) in men and 2.42 (1.91 to 3.06, P < 0.001) in women. CONCLUSION: Proteinuria was a strong, independent predictor of ESRD in a mass screening setting. Even a slight increase in proteinuria was an independent risk factor for ESRD. Therefore, asymptomatic proteinuria warrants further work-up and intervention.     

Outcomes of stage 1–5 chronic kidney disease in Mainland China

Objective: This study aims to quantify and compare the risks of death and end stage renal disease (ESRD) in a prospective cohort of patients with chronic kidney disease (CKD) stages 1–5 under renal management clinic at Peking University Third Hospital and to evaluate the risk factors associated with these two outcomes. Method: This was a prospective cohort study. Finally, 1076 patients at CKD stage 1–5 short of dialysis were recruited from renal management clinic. Patients were monitored for up to Dec, 2011 or until ESRD and death. Glomerular filtration rate was estimated (eGFR) according to the using the CKD Epidemiology Collaboration (CKD-EPI) formula. Results: At the end of follow-up, 111 patients (10.1%) developed ESRD (initiated dialysis or kidney transplantation (ESRD)) and 24 patients (2.2%) had died. There were more ESRD occurrence rate in patients with baseline diabetic nephropathy, lower eGFR, hemoglobin <100?g/L and 24?h urinary protein excretion ≥3.0?g. By multivariate Cox regression model, having heavy proteinuria and CKD stage were the risk factors of ESRD. For all-cause mortality, the most common cause was cardiovascular disease, followed by infectious disease and cancer. But we failed to conclude any significant variable as risk factors for mortality in multivariate analysis. Conclusions: Our study indicated that baseline diabetic nephropathy, lower hemoglobin level, lower baseline GFR and heavy proteinuria were the risk factors of ESRD. In this CKD cohort, patients were more likely to develop ESRD than mortality, and cardiovascular mortality was the leading cause of death, and then followed by infectious diseases and cancer in this population.     

Vertebral Fracture Risk in Diabetic Elderly Men: The MrOS Study

Type 2 diabetes (T2DM) is associated with a significant increase in risk of nonvertebral fractures, but information on risk of vertebral fractures (VFs) in subjects with T2DM, particularly among men, is lacking. Furthermore, it is not known whether spine bone mineral density (BMD) can predict the risk of VF in T2DM. We sought to examine the effect of diabetes status on prevalent and incident vertebral fracture, and to estimate the effect of lumbar spine BMD (areal and volumetric) as a risk factor for prevalent and incident morphometric vertebral fracture in T2DM (n = 875) and nondiabetic men (n = 4679). We used data from the Osteoporotic Fractures in Men (MrOS) Study, which enrolled men aged ≥65 years. Lumbar spine areal BMD (aBMD) was measured with dual‐energy X‐ray absorptiometry (DXA), and volumetric BMD (vBMD) by quantitative computed tomography (QCT). Prevalence (7.0% versus 7.7%) and incidence (4.4% versus 4.5%) of VFs were not higher in T2DM versus nondiabetic men. The risk of prevalent (OR, 1.05; 95% CI, 0.78 to 1.40) or incident vertebral‐fracture (OR, 1.28; 95% CI, 0.81 to 2.00) was not higher in T2DM versus nondiabetic men in models adjusted for age, clinic site, race, BMI, and aBMD. Higher spine aBMD was associated with lower risk of prevalent VF in T2DM (OR, 0.55; 95% CI, 0.48 to 0.63) and nondiabetic men (OR, 0.66; 95% CI, 0.5 to 0.88) (p for interaction = 0.24) and of incident VF in T2DM (OR, 0.50; 95% CI, 0.41 to 0.60) and nondiabetic men (OR, 0.54; 95% CI, 0.33 to 0.88) (p for interaction = 0.77). Results were similar for vBMD. In conclusion, T2DM was not associated with higher prevalent or incident VF in older men, even after adjustment for BMI and BMD. Higher spine aBMD and vBMD are associated with lower prevalence and incidence of VF in T2DM as well as nondiabetic men. © 2017 American Society for Bone and Mineral Research.     

Association between body mass index and chronic kidney disease in men and women: population-based study of Malay adults in Singapore.

BACKGROUND: In contrast to previous studies from western populations, studies from Japan reported a positive association between body mass index (BMI) and chronic kidney disease (CKD) among men but not women. In this context, we examined the relationship between BMI and CKD, by gender, in a study of Malay adults from Singapore. METHODS: This was a population-based cross-sectional sample of adults (n = 2783, 53% women, aged 49-80 years), free of clinical cardiovascular disease. The outcome of interest was presence of CKD [estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m(2) (n = 517)]. The statistical methods used were logistic and nonparametric logistic regressions. RESULTS: Higher BMI levels were found to be positively associated with CKD among Malay men. Among men, compared to BMI quartile 1 (<23 kg/m(2)), the multivariable odds ratio (OR) [95% confidence intervals (CI)] of CKD was 3.12 (1.97-4.94) in quartile 2 (23-24.9 kg/m(2)), 2.49 (1.63-3.79) in quartile 3 (25-29.9 kg/m(2)) and 3.70 (2.13-6.42) in quartile 4 (>or=30 kg/m(2)); P-trend < 0.0001. In contrast, among women BMI levels were not associated with CKD; P-trend = 0.32. In nonparametric models, among men, the observed positive association between BMI and CKD appeared to be present across the full range of BMI values, without any threshold. In contrast, among women, results from nonparametric models were consistent with the conclusion of a lack of association between BMI and CKD. CONCLUSIONS: Higher BMI levels were positively associated with CKD among men but not women in a population-based study from Singapore. These results are consistent with the hypothesis of a male gender-specific association between BMI and CKD among Asians.     

Prognostic importance of clinic and home blood pressure recordings in patients with chronic kidney disease

Blood pressure (BP) measured only in the clinic substantially misclassifies hypertension in patients with chronic kidney disease (CKD). The role of out-of-clinic recordings of BP in predicting end-stage renal disease (ESRD) and death in patients with CKD is unknown. A prospective cohort study was conducted in 217 Veterans with CKD. BP was measured at home and in the clinic by 'routine' and standardized methods. Patients were followed over a median of 3.5 years to assess the end points of total mortality, ESRD or the composite outcome of ESRD or death. Home BP was 147.0+/-21.4/78.3+/-11.6 mmHg and clinic BPs were 155.2+/-25.6/84.7+/-14.2 mmHg by standardized method and 144.5+/-24.2/75.4+/-14.7 mmHg by the 'routine' method. The composite renal end point occurred in 75 patients (34.5%), death in 52 patients (24.0%), and ESRD in 36/178 patients (20.2%). One standard deviation (s.d.) increase in systolic BP increased the risk of renal end point by 1.27 (95% confidence interval (CI) 1.01-1.60) for routine clinic measurement, by 1.69 (95% CI 1.32-2.17) for standardized clinic measurement and by 1.84 (95% CI 1.46-2.32) for home BP recording. One s.d. increase in home systolic BP increased the risk of ESRD by 1.74 (95% CI 1.04-2.93) when adjusted for standardized clinic systolic BP, proteinuria, estimated glomerular filtration rate, and other risk factors. In patients with CKD, BPs obtained at home are a stronger predictor of ESRD or death compared to BPs obtained in the clinic. Systolic home BP is an independent predictor for ESRD.     

Proteinuria and decreased body mass index as a significant risk factor in developing end-stage renal disease

Background  Body mass index (BMI) is a significant predictor of developing end-stage renal disease (ESRD). The relation between a change in BMI (ΔBMI) and the incidence of ESRD has not been examined in any large epidemiologic studies. Methods  We determined the ΔBMI in subjects who participated in the Okinawa General Health Maintenance Association (OGHMA) screenings in 1983 and again in 1993. Screenees were free of ESRD at the 1993 screening and were then monitored until the end of 2000 to determine whether they developed ESRD. Participants were identified using ID numbers, birthdates, and other identifiers. Details of every ESRD patient treated in Okinawa are maintained in an independent community-based dialysis registry. Multivariate logistic analyses were performed to determine the significance of a ΔBMI on the incidence of ESRD using SAS. The ethics committee of the OGHMA approved the study protocol. Only coded data were used for this study. Results  Among the 92,364 subjects aged 30–89 years screened in 1983, 29,011 (31.4%) returned for the 1993 screening. The median ΔBMI was 2.1%, and the subjects were divided into two groups: ΔBMI < 2.1% (G1) and ΔBMI ≥ 2.1% (G2). The cumulative incidence of ESRD was 0.31% in G1 (ESRD in 44) and 0.14% in G2 (ESRD in 21). The odds ratio (95% confidence interval) of developing ESRD based on a ΔBMI was 2.268 (1.284–4.000, P < 0.01) after adjusting for age, sex, systolic blood pressure, BMI in 1983, and proteinuria. Conclusion  The findings of the present study suggest that a ΔBMI is an independent risk factor for the incidence of ESRD, especially for those with proteinuria. The reasons for the BMI change were not recorded in this study. Unintentional weight loss, however, might warrant evaluation for the presence or progression of chronic kidney disease.     

Association of transforming growth factor-β1 polymorphisms with the risk of chronic kidney diseases

Abstract

The association of transforming growth factor-β1 (TGF-β1) polymorphisms with the risk of chronic kidney diseases (CKD) remains elusive. We aimed to perform a meta-analysis to evaluate the relationship between TGF-β1 polymorphisms and the susceptibility to CKD. Association studies were searched according to a defined criteria using electronic databases. The strength of association between TGF-β1 polymorphisms and CKD risk was evaluated by odds ratio (OR) with the corresponding 95% confidence interval (CI). Nine case–control studies were identified. T allele at the +869 T/C polymorphism was associated with a lower risk of CKD in Asians (p?=?0.003). TT genotype at the +869 T/C polymorphism was associated with a lower risk of CKD in overall populations and Asians (p?=?0.007 and <10^?4, respectively). CC genotype at the +869 T/C polymorphism was associated with the risk of CKD in Asians (p?=?0.002). T allele at the ?509 T/C polymorphism was associated with the risk of CKD in overall populations and Asians (p?=?0.044 and 0.050, respectively). TT genotype at the ?509 T/C polymorphism was associated with CKD risk in overall populations, Caucasians and Asians (p?<?10^?4, <10^?4, and <10^?4, respectively). No evidence of significant publication bias was noted. In conclusion, T allele at the +869 T/C polymorphism may be a protective factor against CKD risk in Asians. TT genotype at the +869 T/C polymorphism may be an indicator of lower risk of CKD in overall populations and Asians. CC genotype at the +869 T/C polymorphism may predict the susceptibility to CKD in Asians. T allele at the ?509 T/C polymorphism may be an indicator of CKD risk in overall populations and Asians. TT genotype at the ?509 T/C polymorphism was a risk factor for CKD onset in overall populations, Caucasians and Asians.     

Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis

Acute kidney injury may increase the risk for chronic kidney disease and end-stage renal disease. In an attempt to summarize the literature and provide more compelling evidence, we conducted a systematic review comparing the risk for CKD, ESRD, and death in patients with and without AKI. From electronic databases, web search engines, and bibliographies, 13 cohort studies were selected, evaluating long-term renal outcomes and non-renal outcomes in patients with AKI. The pooled incidence of CKD and ESRD were 25.8 per 100 person-years and 8.6 per 100 person-years, respectively. Patients with AKI had higher risks for developing CKD (pooled adjusted hazard ratio 8.8, 95% CI 3.1-25.5), ESRD (pooled adjusted HR 3.1, 95% CI 1.9-5.0), and mortality (pooled adjusted HR 2.0, 95% CI 1.3-3.1) compared with patients without AKI. The relationship between AKI and CKD or ESRD was graded on the basis of the severity of AKI, and the effect size was dampened by decreased baseline glomerular filtration rate. Data were limited, but AKI was also independently associated with the risk for cardiovascular disease and congestive heart failure, but not with hospitalization for stroke or all-cause hospitalizations. Meta-regression did not identify any study-level factors that were associated with the risk for CKD or ESRD. Our review identifies AKI as an independent risk factor for CKD, ESRD, death, and other important non-renal outcomes.     

Association of single measurements of dipstick proteinuria, estimated glomerular filtration rate, and hematocrit with 25-year incidence of end-stage renal disease in the multiple risk factor intervention trial

The incidence of ESRD is increasing rapidly. Limited information exists regarding early markers for the development of ESRD. This study aimed to determine over 25 yr the risk for ESRD associated with proteinuria, estimated GFR (eGFR), and hematocrit in men who did not have identified kidney disease and were randomly assigned into the Multiple Risk Factor Intervention Study (MRFIT). A total of 12,866 men who were at high risk for heart disease were enrolled (1973 to 1975) and followed through 1999. Renal replacement therapy was ascertained by matching identifiers with the United States Renal Data System's data; vital status was from the National Death Index. Men who initiated renal replacement therapy or died as a result of kidney disease were deemed to have developed ESRD. Dipstick urine for proteinuria, eGFR, and hematocrit were related to development of ESRD. During 25 yr, 213 (1.7%) men developed ESRD. Predictors of ESRD were dipstick proteinuria of 1+ or > or =2+ (hazard ratio [HR] 3.1 [95% confidence interval (CI) 1.8 to 5.4] and 15.7 [95% CI 10.3 to 23.9] respectively) and an eGFR of <60 ml/min per 1.73 m(2) (HR 2.4; 95% CI 1.5 to 3.8). Correlation between eGFR and serum creatinine was 0.9; the risk for ESRD with a 1-SD difference of each was identical (HR 1.21). Bivariate analysis demonstrated a 41-fold increase in ESRD risk in those with an eGFR <60 ml/min per 1.73 m(2) and > or =2+ proteinuria (95% CI 15.2 to 71.1). There was no association between hematocrit and ESRD. Other baseline measures that independently predicted ESRD included age, cigarette smoking, BP, low HDL cholesterol, and fasting glucose. Among middle-aged men who were at high risk for cardiovascular disease but had no clinical evidence of cardiovascular disease or significant kidney disease, dipstick proteinuria and an eGFR value <60 ml/min per 1.73 m(2) were strong predictors of long-term development of ESRD. It remains unknown whether intervention for proteinuria or early identification of those with chronic kidney disease reduces the risk for ESRD.     

Metabolic syndrome and chronic kidney disease in Okinawa, Japan

We assessed the prevalence of chronic kidney disease (CKD) in a hospital-based screening program in Okinawa, Japan. The significance of metabolic syndrome as a determinant of CKD was examined using multivariate logistic regression analysis. A total of 6980 participants, aged 30-79 years, participated in a screening program in Tomishiro Chuo Hospital. Metabolic syndrome was defined according to the criteria of the Adult Treatment Panel III (ATP III). Data were also analyzed according to the modified criteria of the National Cholesterol Education Program (NCEP) that defines abdominal obesity as a waist circumference of > oe =85 cm in men and > or =90 cm in women. CKD was defined as dipstick proteinuria (> or =1+) or a reduced glomerular filtration rate (GFR). GFR was estimated using the abbreviated Modification of Diet in Renal Disease (MDRD) formula. The prevalence of metabolic syndrome and CKD was 12.8 and 13.7%, respectively. Metabolic syndrome was a significant determinant of CKD (adjusted odds ratio (OR) 1.537 and 95% confidence interval (CI) 1.277-1.850, P<0.0001). The adjusted OR (95% CI) was 1.770 (1.215-2.579, P=0.0029) for those with four metabolic syndrome risk factors compared to those with no metabolic syndrome risk factors. Metabolic syndrome was a significant determinant for younger participants (<60 years; OR 1.686, 95% CI 1.348-2.107, P<0.0001), but not for older participants (> or =60 years; OR 1.254, 95% CI 0.906-1.735, NS). The relationship between the number of metabolic syndrome risk factors and the prevalence of CKD was linear using the modified criteria. The results suggest that metabolic syndrome is a significant determinant of CKD in men under 60 years of age, in Okinawa, Japan.     

Medicare patients with cardiovascular disease have a high prevalence of chronic kidney disease and a high rate of progression to end-stage renal disease

The risk of progression to ESRD among individuals with cardiovascular disease and chronic kidney disease (CKD) is not well defined. The purpose of this study was to describe the risk of ESRD among patients with cardiovascular disease. Charts were abstracted for randomly selected hospitalized Medicare beneficiaries with a diagnosis of either congestive heart failure (CHF) or acute myocardial infarction (AMI). The prevalence of CKD, based on the estimated modified diet in renal disease GFR of <60 ml/min per m2, was 60.4% of CHF patients and 51.7% of AMI patients. When compared with patients without CKD, the 30-d readmission rate was higher for CHF patients with CKD (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.18 to 2.44) and for AMI patients with CKD (OR, 1.78; 95% CI, 1.17 to 2.70). CHF patients (OR, 1.62; 95% CI, 1.15 to 2.30) and AMI patients (OR, 3.10; 95% CI, 1.98 to 4.84) with CKD were more likely to die during the year after discharge from the hospital. ESRD after discharge occurred in nine of 517 patients with AMI and 24 of 640 patients with CHF. CKD increased the risk of ESRD among CHF patients (OR, 34.5; 95% CI, 4.23 to 279.43) and AMI patients (0 and 3% for those without and with CKD, respectively). At discharge, 18% of AMI patients and 21% of CHF patients with CKD were discharged with a diagnosis of renal disease. CKD is highly prevalent among patients with cardiovascular disease and is associated with increased risk of adverse outcomes, including progression to ESRD. This study suggests that opportunities may exist to improve the detection of CKD in these patients who are hospitalized with cardiovascular disease.