Jer-Ming Chang

Association of Hyperuricemia with Renal Outcomes, Cardiovascular Disease, and Mortality

BACKGROUND AND OBJECTIVES Hyperuricemia is an independent risk factor for mortality, cardiovascular disease, and renal disease in general population. However, the relationship between hyperuricemia with clinical outcomes in CKD remains controversial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The study investigated the association between uric acid with all-cause mortality, cardiovascular events, renal replacement therapy, and rapid renal progression (the slope of estimated GFR was less than -6 ml/min per 1.73 m(2)/y) in 3303 stages 3-5 CKD patients that were in the integrated CKD care system in one medical center and one regional hospital in southern Taiwan. RESULTS In all subjects, the mean uric acid level was 7.9 ± 2.0 mg/dl. During a median 2.8-year follow-up, there were 471 (14.3%) deaths, 545 (16.5%) cardiovascular events, 1080 (32.3%) participants commencing renal replacement therapy, and 841 (25.5%) participants with rapid renal progression. Hyperuricemia increased risks for all-cause mortality and cardiovascular events (the adjusted hazard ratios for quartile four versus quartile one of uric acid [95% confidence interval] were 1.85 [1.40-2.44] and 1.42 [1.08-1.86], respectively) but not risks for renal replacement therapy (0.96 [0.79-1.16]) and rapid renal progression (1.30 [0.98-1.73]). CONCLUSIONS In stages 3-5 CKD, hyperuricemia is a risk factor for all-cause mortality and cardiovascular events but not renal replacement therapy and rapid renal progression.

Brachial-Ankle Pulse Wave Velocity and Rate of Renal Function Decline and Mortality in Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Increased arterial stiffness was reported to be associated with decreased estimated GFR (eGFR). Previous studies suggested that arterial stiffness might play a role in renal function progression in patients with chronic kidney disease (CKD). The aim of this study was to investigate whether there was an independent association between brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, and renal function progression in CKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This longitudinal study enrolled 145 patients with CKD stages 3 to 5. The baPWV was measured by using an ABI-form device. The change in renal function was estimated by eGFR slope. The study endpoints were defined as commencement of dialysis or death. RESULTS After a stepwise multivariate analysis, the eGFR slope was positively associated with baseline eGFR and negatively associated with hypertension and baPWV (β=-0.165, P=0.033). Seventeen patients entering dialysis, and eight deaths were recorded. Multivariate forward Cox regression analysis identified that higher baPWV (hazard ratio, 1.001; P=0.001), lower baseline eGFR, and higher serum phosphate level were independently associated with progression to commencement of dialysis or death. CONCLUSIONS Our results show an independent association between baPWV and renal function decline and progression to commencement of dialysis or death in patients with CKD. Screening CKD patients by means of baPWV may help identify a high-risk group of rapid renal function decline and progression to commencing dialysis or death.

Echocardiographic parameters are independently associated with rate of renal function decline and progression to dialysis in patients with chronic kidney disease.

BACKGROUND AND OBJECTIVES Cardiac abnormalities were frequently noted in patients with chronic kidney disease (CKD). This study is designed to assess whether echocardiographic parameters are associated with rate of renal function decline and progression to dialysis in CKD stage 3 to 5 patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This longitudinal study enrolled 415 patients. The renal end point was defined as commencement of dialysis. The change in renal function was measured by estimated GFR (eGFR) slope. RESULTS Progression to dialysis was predicted by wide pulse pressure, low albumin, low hemoglobin, high calcium-phosphorous product, proteinuria, diuretics use, and concentric left ventricular hypertrophy (LVH) (hazard ratio, 2.03; 95% confidence interval [CI], 1.00 to 4.10; P = 0.05). The eGFR slope was negatively associated with total cholesterol, uric acid, proteinuria, diuretics use, and left atrial (LA) diameter (change in slope, -0.50; 95% CI, -0.89 to -0.11; P = 0.01) and positively associated with albumin and left ventricular ejection fraction (LVEF) (change in slope, 0.06; 95% CI, 0.03 to 0.08; P < 0.001). CONCLUSIONS Our study in patients of CKD stage 3 to 5 demonstrated that concentric LVH was associated with progression to dialysis, and that increased LA diameter and decreased LVEF were associated with faster renal function decline. Echocardiography may help identify high-risk groups with progressive decline in renal function to dialysis and rapid progression of renal dysfunction in CKD stage 3 to 5 patients.

Hepatitis C Virus Infection Increases Risk of Developing End-Stage Renal Disease Using Competing Risk Analysis

Background Chronic kidney disease (CKD) and hepatitis C virus (HCV) infection are closely linked and both increase patient mortality. The association of HCV and risk of developing end-stage renal disease (ESRD) has not been analyzed with competing risk model. Method We enrolled a prospective cohort of 4,185 patients (mean age, 62 years; 41% female) registered in the CKD integrated care program at two affiliated hospitals of Kaohsiung Medical University in Taiwan between November 11, 2002 and May 31, 2009. With competing risk model, we analyzed the association of HCV infection, defined by seropositive of anti-HCV antibody, and hepatitis B virus (HBV) infection, defined by seropositive of HBV surface antigen, with the risk of entering ESRD. Results The prevalence of HCV infection was 7.6% and it increased with the CKD stages (trend test, P<0.001), while the prevalence of HBV infection was 7.4% and no specific trend among CKD stages (tend test, P = 0.1). During the 9,101 person-year follow-up period, there were 446 death and 1,205 patients entering ESRD. After adjusting death as the competing risk, the estimated 5-year cumulative incidence rate of ESRD among patients with and without HCV infection were 52.6% and 38.4%, respectively (modified log-rank, P<0.001). Multivariable analysis showed that HCV infection, but not HBV infection, had higher risk of developing ESRD compared with cases without infection (HCV, HR: 1.32, 95% CI: 1.07–1.62; HBV, HR: 1.10, 95% CI: 0.89–1.35). Subgroup analyses showed consistent results. Conclusions With death-adjusted competing risk analysis, HCV infection is associated with an increased risk of developing ESRD in CKD cohort.

Impact of renal failure on the outcome of dengue viral infection.

BACKGROUND AND OBJECTIVES In the 2002 dengue outbreak in Taiwan, some fatal cases had the underlying disease of renal failure (RF). Physicians faced difficulty in diagnosis and treatment of these patients; however, the impacts of RF on the clinical presentations and outcomes of dengue infection have not been reported previously. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A retrospective review was conducted of medical records, clinical presentations, laboratory findings, and underlying diseases for all cases of dengue infection in a medical center. Characteristics and outcomes of dengue-infected patients with and without RF were compared. RESULTS From January 2002 through January 2003, 519 dengue-infected patients were enrolled, including 412 patients with classical dengue fever (DF) and 107 patients with dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Twelve patients died in this outbreak, and all had DHF/DSS. Twenty-one (4.0%) patients were defined as being in the RF group. The RF group had a higher mortality rate than non-RF group (28.6 versus 1.2%; P < 0.001). The severity of GFR impairment was associated with higher percentages of DHF/DSS (P = 0.029) and mortality (P < 0.001). Differences in symptoms/signs and laboratory abnormalities between DF and DHF/DSS were significant in the non-RF group but not apparent in the RF group. CONCLUSIONS The diagnosis and management of dengue infection among patients with RF must be cautious, because complicated clinical courses with a higher mortality rate were well observed.

Ankle brachial index as a predictor for mortality in patients with chronic kidney disease and undergoing haemodialysis.

Aim:  The ankle brachial index (ABI) is a marker for peripheral artery disease and can predict mortality in advanced chronic kidney disease (CKD) and haemodialysis patients, respectively. However, it is seldom studied in Taiwan, an area with high prevalence of CKD and end‐stage renal disease. The aim of this study was to investigate the predictors for mortality by using ABI value in patients with CKD and undergoing haemodialysis in Taiwan.

Association of Dyslipidemia with Renal Outcomes in Chronic Kidney Disease

Dyslipidemia is highly prevalent in patients with chronic kidney disease (CKD) and the relationship between dyslipidemia with renal outcomes in patients with moderate to advanced CKD remains controversial. Hence, our objective is to determine whether dyslipidemia is independently associated with rapid renal progression and progression to renal replacement therapy (RRT) in CKD patients. The study analyzed the association between lipid profile, RRT, and rapid renal progression (estimated glomerular filtration rate [eGFR] slope <−6 ml/min/1.73 m2/yr) in 3303 patients with stages 3 to 5 CKD. During a median 2.8-year follow-up, 1080 (32.3%) participants commenced RRT and 841 (25.5%) had rapid renal progression. In the adjusted models, the lowest quintile (hazard ratios [HR], 1.23; 95% confidence interval [CI], 1.01 to 1.49) and the highest two quintiles of total cholesterol (HR, 1.25; 95% CI, 1.02 to 1.52 and HR, 1.35; 95% CI, 1.11 to 1.65 respectively) increased risks for RRT (vs. quintile 2). Besides, the highest quintile of total cholesterol was independently associated with rapid renal progression (odds ratio, 1.36; 95% CI, 1.01 to 1.83). Our study demonstrated that certain levels of dyslipidemia were independently associated with RRT and rapid renal progression in CKD stage 3–5. Assessment of lipid profile may help identify high risk groups with adverse renal outcomes.

Prevalence and Risk Factors for CKD in Spouses and Relatives of Hemodialysis Patients

BACKGROUND A higher prevalence of chronic kidney disease (CKD) has been found in genetic relatives of patients with end-stage renal disease. However, the risk of CKD in nongenetic spouses of patients with end-stage renal disease is still unknown. STUDY DESIGN Cross-sectional study. SETTING & PARTICIPANTS 196 first- and second-degree relatives and 95 spouses of 178 hemodialysis (HD) patients were enrolled. Two sex- and age-stratified matched counterpart controls were randomly selected from the population of a community screening program for CKD. PREDICTORS Relatives or spouses of HD patients and kidney disease risk factors. OUTCOMES Prevalence of CKD (albuminuria or low estimated glomerular filtration rate). MEASUREMENT Albuminuria (urine albumin-creatinine ratio > or = 30 mg/g), low estimated glomerular filtration rate (<60 mL/min/1.73 m(2)), and kidney disease risk factors of age, hypertension, diabetes mellitus, metabolic syndrome, and lifestyle. RESULTS A significantly higher prevalence of CKD was found in relatives (15.8% vs 7.5%; P = 0.01) and spouses (41.1% vs 15.8%; P < 0.001) of HD patients compared with their counterpart controls. Multiple logistic regression analysis showed that age (OR, 1.05) and hypertension (OR, 3.13) were significant independent risk factors for CKD in relatives of HD patients, whereas diabetes mellitus (OR, 3.51) was a significant risk factor for CKD in spouses of HD patients. For all pooled participants, being relatives (OR, 2.55) or spouses (OR, 2.80) of HD patients, age (OR, 1.06), female sex (OR, 1.81), diabetes mellitus (OR, 3.95), hypertension (OR, 1.85), and hyperuricemia (OR, 2.06) were independent significant risk factors for CKD. LIMITATIONS Cross-sectional research design, single laboratory measurement, and limited numbers of participants. CONCLUSIONS A comprehensive screening program for CKD is equally important in both relatives and spouses of HD patients, especially for participants with the renal risk factors of older age, hypertension, and diabetes mellitus. Spousal concordance of CKD suggests that the shared environmental factors and health behaviors might have important roles in the development of CKD.

Early Nephrology Referral Is Associated With Prolonged Survival in Hemodialysis Patients Even After Exclusion of Lead-Time Bias

Background:Early nephrology referral (ER) has been suggested to lower morbidity and mortality in dialysis patients, but the nature of the association has been criticized as possibly because of lead-time bias. This study aims to evaluate if ER is associated with improved survival of hemodialysis patients when the lead-time bias is excluded. Methods:A total of 192 hemodialysis patients from a medical center and a regional hospital were enrolled in the period from January 1997 to December 2006. ER and late referral (LR) were defined as referral to nephrologists greater or less than 6 months, respectively, before the initiation of hemodialysis. Follow-up of clinical course in all patients was timed from the date at which estimate glomerular filtration rate was estimated to be 15 mL/min/1.73m2. The relative overall survival was analyzed by Cox-regression adjusted for their demographic and comorbid conditions Results:Compared with LR patients, ER patients were less likely to have hypoalbuminemia in the beginning of hemodialysis, more likely to have received erythropoietin or phosphate binder therapy, more likely to have a vascular access created before the first hemodialysis, and had a slower rate of renal function decline before hemodialysis. In multivariate analysis, LR (hazard ratio: 2.827; P = 0.049) and diabetes mellitus were both independently associated with increased mortality risk. The survival benefits of ER seem to be originated from the period before initiation of renal replacement therapy. Conclusions:Our findings show that ER is significantly associated with prolonged survival after exclusion of lead-time bias, which is consistent with ER being associated with better clinical outcomes in hemodialysis patients.

Significant Correlation between Ankle-Brachial Index and Vascular Access Failure in Hemodialysis Patients

BACKGROUND AND OBJECTIVES Vascular access failure (VAF) is associated with increased morbidity and mortality in hemodialysis patients. The most common cause of VAF is stenosis at the arteriovenous anastomosis because of abnormal neointimal proliferation and extracellular matrix deposition. These two changes are also observed in the classic atheroma, which means atherosclerotic lesions and venous stenosis in VAF may share some similar pathogenic mechanisms. The ankle-brachial index (ABI) is a reliable marker for atherosclerosis. The aim of this study was to evaluate the relationship between ABI <0.9 and VAF. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS All routine hemodialysis patients in one regional hospital were included except for six patients refusing ABI examinations and four patients with atrial fibrillation. Finally, 225 patients formed our study group. The study subjects were observed from arteriovenous access creation until the first episode of VAF. The mean observation period was 42.2 +/- 42.8 mo. The relative VAF risk was analyzed by Cox-regression methods with adjustments for demographic and comorbid conditions. RESULTS VAF episodes were recorded in 111 patients. In multivariate analysis, ABI <0.9 (hazard ratio, 1.893; P = 0.039), vascular access type of arteriovenous graft (P = 0.004), and serum triglyceride level (P = 0.043) were positively associated with VAF, and serum parathyroid hormone level (P = 0.043) was negatively associated with VAF. CONCLUSIONS Our findings show that ABI <0.9 is significantly correlated with increased VAF. Screening hemodialysis patients by means of ABI may help to identify a high-risk group for VAF.