The role of physical activity in chronic kidney disease in the presence of diabetes mellitus: a prospective cohort study.

BACKGROUND/AIMS: Although the effect of exercise on health is well established, nephrologists seldom consider physical activity in the treatment of chronic kidney disease (CKD) or CKD in the presence of diabetes mellitus (DM/CKD). The aim of the present study was to analyze the benefits of leisure-time physical activity (LTPA) in DM/CKD. METHODS: A total of 445,075 adult participants who underwent a medical screening program between 1996 and 2008 were prospectively recruited. Of these, 7,863 DM/CKD subjects were identified. Each participant was categorized according to LTPA level (a product of duration and intensity) as inactive, low-active or fully active. Hazard ratios (HRs) for mortality risk were calculated. RESULTS: Fully active LTPA was associated with lower odds of DM/CKD development and lower risk of mortality among patients with DM/CKD in a dose-response relationship. The fully active and low-active DM/CKD groups had a 26% (HR 0.74, 95% CI 0.66-0.85) and 13% (HR 0.87, 95% CI 0.75-1.01) lower risk of all-cause mortality, respectively, in comparison to the inactive group. The association of exercise with mortality rate reduction was more pronounced among DM/CKD subjects (mortality rate reduction of 446.5 per 100,000 person-years) than among subjects with diabetes alone or CKD alone. CONCLUSION: Exercise, at the recommended level or more, is associated not only with lower odds of DM/CKD but also with a 26% lower mortality risk among DM/CKD patients. Nephrologists should encourage all DM/CKD subjects to be physically active

Is high serum uric acid a risk marker or a target for treatment? Examination of its independent effect in a large cohort with low cardiovascular risk.

BACKGROUND: Cohort studies evaluating increased uric acid level as a cardiovascular disease (CVD) risk factor have shown variable results; studies are particularly lacking in lower risk populations. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 484,568 adults participating in a medical screening program in Taiwan since 1994 were followed up for a median of 8.5 years. Two subgroups were constructed: the first (n = 246,697; 51%) excluded participants with either overt CVD or overt CVD risk factors (including hypertension, diabetes, obesity, and hypertriglyceridemia) and the second (n = 157,238; 32%) further excluded individuals with early-stage CVD risk factors (including prehypertension, prediabetes, overweight, and borderline hypertriglyceridemia). PREDICTOR: Serum uric acid. OUTCOMES & MEASUREMENTS: All-cause and CVD mortality risk assessed using Cox proportional hazards models for categorical and continuous serum uric acid levels. As applicable, models adjusted for 14 variables. Population-attributable fraction was applied to compare contributions to mortality between high uric acid level and other CVD risk factors. RESULTS: In the total cohort, mean age was 41.4 +/- 14.0 years and 26.2% had serum uric acid levels >or=7 mg/dL. Through 2007, there were 16,246 deaths (3.4% of all participants), with 35.2% of deaths occurring in individuals with hyperuricemia. Adjusted HRs associated with serum uric acid levels >or=7 mg/dL for all-cause and CVD mortality were 1.10 (95% CI, 1.04-1.17) and 1.38 (95% CI, 1.20-1.58), respectively. In individuals with hyperuricemia, 64.3% had overt CVD risk factors and 82.5% had either overt or early-stage CVD risk factors. Individuals with serum uric acid levels >or=8 mg/dL without overt CVD risk factors constituted 13.5% of the total study population with hyperuricemia; in analyses excluding those with overt CVD risk factors, serum uric acid level >or=8 mg/dL was significantly associated with all-cause and CVD mortality, with HRs of 1.37 (95% CI, 1.18-1.60) and 2.30 (95% CI, 1.51-3.49), respectively. In the subgroup of those with serum uric acid levels >or=8 mg/dL but who lacked both overt and early-stage CVD risk factors, the HRs for all-cause and CVD mortality were also significant and were 1.39 (95% CI, 1.08-1.78) and 2.38 (95% CI, 1.24-4.54), respectively. HRs for individuals with the same risk profiles but with serum uric acid of 7.0-7.9 mg/dL were not significant. In all groups, inclusion of proteinuria and glomerular filtration rate in models substantially attenuated the association between uric acid level and outcomes. High uric acid levels contributed a relatively insignificant portion to mortality (1.2%) and CVD deaths (4.5%) in this population. LIMITATIONS: A single measurement of uric acid was used. CONCLUSION: Increased serum uric acid level is a minor, but significant, risk factor for all-cause and CVD mortality. However, except for a small proportion (13.5%), increased serum uric acid level is more a risk marker than a target for treatment and is not an independent risk. Determining appropriate groups to target in clinical trials for uric acid-lowering therapy is critical.

Mortality risks for all causes and cardiovascular diseases and reduced GFR in a middle-aged working population in Taiwan.

BACKGROUND: Effects of decreased estimated glomerular filtration rate (eGFR) on cardiovascular disease (CVD) mortality are uncertain in Chinese general populations. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 17,026 adults 50 years and older in Taiwan. A subset of 7,968 had repeated measurements. PREDICTOR: Decreased eGFR and its progression. eGFR was calculated from serum creatinine level by using the Modification of Diet in Renal Disease Study equation. OUTCOMES: Mortality from all causes and CVD, including coronary heart disease (CHD) and stroke, from the National Death Registry. MEASUREMENTS: Hazard ratios (HRs) and Kaplan-Meier survival curves were calculated for participants with a moderate to severe decrease in eGFR (<60 mL/min/1.73 m(2)) compared with those with normal eGFR (> or =90 mL/min/1.73 m(2)). HR of a rapid decrease (> or =20%) in eGFR was also calculated. RESULTS: Mean age of all participants was 57.2 +/- 5.2 (SD) years. We observed 1,682 deaths in 15 years of follow-up. Participants with a moderate to severe decrease in eGFR had increased HRs for mortality from all causes (1.44; 95% confidence interval [CI], 1.22 to 1.70), CVD (1.90; 95% CI, 1.36 to 2.65), CHD (2.07; 95% CI, 1.26 to 3.41), and stroke (2.16; 95% CI, 1.29 to 3.62) after adjusting for confounders. Decreased eGFR was associated with ischemic stroke, but not hemorrhagic stroke. No significant interaction between decreased eGFR and anemia, diabetes, or smoking was found. There were 660 participants with a 20% or greater decrease in eGFR from baseline during 18 months of follow-up. They had increased HRs for all causes (1.45; 95% CI, 1.13 to 1.86), CVD (2.48; 95% CI, 1.58 to 3.89), CHD (2.14; 95% CI, 1.07 to 4.29), and stroke (2.79; 95% CI, 1.45 to 5.36) compared with those with less than a 20% decrease in eGFR during the same period. LIMITATIONS: Data for proteinuria were not available. Creatinine assay was not calibrated. CONCLUSIONS: A moderate to severe or fast decrease in eGFR was associated with all-cause and CVD mortality in this ethnic Chinese cohort.

All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462 293 adults in Taiwan.

BACKGROUND: Both end-stage renal disease and chronic kidney disease are increasing worldwide; however, the full effect of chronic kidney disease is unknown because mortality risks for all five stages are unavailable. We assessed prevalence and mortality risks for all stages of chronic kidney disease and quantified its attributable mortality in Taiwan. METHODS: The cohort consisted of 462 293 individuals aged older than 20 years who participated in a standard medical screening programme since 1994. As of Dec 31, 2006, we identified 14 436 deaths. Chronic kidney disease was determined by glomerular filtration rate and urinary protein. We estimated national prevalence in Taiwan from the cohort by adjusting age and educational levels. Hazard ratios (HRs) were calculated with Cox proportionate hazards model. We calculated mortality attributable to chronic kidney disease for national population and for low socioeconomic status. FINDINGS: The national prevalence of chronic kidney disease was 11.93% (95% CI 11.66-12.28), but only 3.54% (3.37-3.68) of participants in the cohort were aware of their disorder. Prevalence was substantially higher in the group with low socioeconomic status than in the high status group (19.87% [19.84-19.91] vs 7.33% [7.31-7.35]). 56 977 (12%) of cohort participants had chronic kidney disease; those with disease had 83% higher mortality for all cause (HR 1.83 [1.73-1.93]) and 100% higher for cardiovascular diseases (2.00 [1.78-2.25]), in a cohort that was observed for 13 years with median follow-up of 7.5 years (IQR 4.0-10.1). 10.3% (95% CI 9.57-11.03) of deaths in the entire population were attributable to chronic kidney disease, but 17.5% (16.27-18.67) of deaths in the low socioeconomic status population. 2350 (39%) deaths occurred before 65 years of age in those with chronic kidney disease. Regular users of Chinese herbal medicines had a 20% (odds ratio 1.20 [1.16-1.24]) increased risk of developing chronic kidney disease. INTERPRETATION: The high prevalence of chronic kidney disease and its associated all-cause mortality, especially in people with low socioeconomic status, make reduction of this disorder a public-health priority. Promotion of its recognition through the general public knowing their glomerular filtration rate and testing their urine is crucial to reduce premature deaths from all causes and to attenuate this global epidemic.