Association of serum total bilirubin with renal outcome in Japanese patients with stages 3-5 chronic kidney disease.

OBJECTIVE: Serum bilirubin has been reported to be associated with the progression of kidney disease in patients with diabetic nephropathy. Less is known, however, about the relationship between bilirubin and chronic kidney disease (CKD) of other etiologies. This study was designed to clarify whether serum total bilirubin concentration is associated with kidney disease progression in patients with CKD independent of etiology. MATERIALS AND METHODS: This prospective observational study enrolled 279 consecutive patients with stages 3-5 CKD. The renal endpoint was the composite of the doubling of serum creatinine or end-stage renal disease requiring dialysis. Patients were divided into three groups by their serum total bilirubin concentrations: ≤0.3 (lowest), 0.4-0.5 (middle), and ≥0.6 (highest) mg/dL. A Cox proportional hazards model was applied to determine the risk factors for poor renal outcome. RESULTS: The median follow-up period was 21months. One-hundred and three patients reached renal end points. After multivariable adjustment, a 0.1mg/dL increase in serum bilirubin was associated negatively with poor renal outcome (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.60-0.87). In addition, after adjustment for confounding factors, including traditional and nontraditional cardiovascular risk factors, the middle (HR 3.14, 95% CI 1.36-8.57) and lowest (HR 4.22, 95% CI 1.81-11.59) bilirubin groups had significantly higher HRs for renal outcome than the highest bilirubin group. CONCLUSIONS: Lower serum bilirubin concentration was independently associated with adverse renal outcomes, suggesting that the measurement of serum bilirubin is useful for predicting kidney disease progression in patients with moderate to severe CKD.

Ankle-brachial blood pressure index predicts cardiovascular events and mortality in Japanese patients with chronic kidney disease not on dialysis.

The ankle-brachial blood pressure index (ABPI) has been recognized to have a predictive value for cardiovascular (CV) events and mortality in general or dialysis populations. However, the associations between ABPI and those outcomes have not been fully investigated in predialysis patients. The present study aimed to clarify the relationships between ABPI and both CV events and mortality in Japanese chronic kidney disease (CKD) patients not on dialysis. In this prospective observational study, we enrolled 320 patients with CKD stages 3-5 who were not on dialysis. At baseline, ABPI was examined and a low ABPI was defined as <0.9. CV events and all-cause deaths were examined in each patient. A Cox proportional hazards model was applied to determine the risk factors for CV events, as well as for mortality from CV and all causes. The median follow-up period was 30 months. CV events occurred in 56 patients and all-cause deaths occurred in 48, including 20 CV deaths. Multivariate analysis showed that age and low ABPI were risk factors for CV events. It was demonstrated that age, a history of cerebrovascular disease and low ABPI were determined as independent risk factors for CV mortality. In addition, age, body mass index and low ABPI were independently associated with all-cause mortality. In patients with CKD, low ABPI during the predialysis period is independently associated with poor survival and CV events, suggesting the usefulness of measuring ABPI for predicting CV events and patient survival in CKD.

Sex differences in the association between serum uric acid levels and cardiac hypertrophy in patients with chronic kidney disease.

Several studies have documented an association between serum uric acid (SUA) concentration and cardiac hypertrophy in hypertensive patients; however, the association remains unclear in chronic kidney disease (CKD) patients. If there is an association between SUA and hypertrophy in these patients, it is unknown whether the association is different between men and women. Our aim in this study is to determine whether SUA is associated with cardiac hypertrophy in CKD patients, focusing on any sex differences. Two hundred sixteen CKD patients (117 men and 99 women) were enrolled in this cross-sectional study. Patients prescribed uric acid-lowering agents and those with congestive heart failure, valvular heart disease, or ischemic heart disease were excluded from this study. Left ventricular mass index (LVMI) and left ventricular hypertrophy (LVH) were assessed using echocardiography. The prevalence of LVH was 58% in men and 47% in women. In multivariate linear regression analysis, SUA levels did not correlate with LVMI in men, whereas SUA was independently associated with LVMI in women (ß=0.27, P=0.02). Multivariate logistic regression analysis also revealed that diabetes mellitus (odds ratio (OR), 4.41; P=0.01) was associated with LVH in men, whereas age (OR, 1.13; P<0.01), hypertension (OR, 7.38; P=0.03) and SUA (OR, 1.91; P=0.03) were associated with LVH in women. In female CKD patients, SUA levels were associated with LVMI and LVH, whereas there was no association in male patients. These observations suggest that an association between SUA levels and the development of cardiac hypertrophy is more likely in women than in men.

Fibroblast growth factor 23 is associated with carotid artery calcification in chronic kidney disease patients not undergoing dialysis: a cross-sectional study.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is an important hormone in the regulation of phosphate metabolism. It is unclear whether FGF23 is associated with carotid artery calcification (CAAC) in predialysis patients. The present study aimed to clarify the relationship between FGF23 and CAAC in patients with chronic kidney disease (CKD) who were not on dialysis. METHODS: One-hundred ninety-five predialysis CKD patients were enrolled in this cross-sectional study. CAAC was assessed using multidetector computed tomography, and the prevalence of CAAC was examined. Intact FGF23 was measured in each patient. The risk factors for CAAC were evaluated using a logistic regression model. RESULTS: We found CAAC in 66% of the patients. The prevalence of CAAC significantly increased across CKD stages: it was 37% in CKD stages 1-2, 58% in stage 3; 75% in stage 4, and 77% in stage 5 (p < 0.01). In multivariate analysis, smoking, diabetes mellitus and log FGF23 were each identified as risk factors for CAAC. The study population was divided in quartiles of FGF23 levels. Compared with the lowest FGF23 quartile, each subsequent quartile had a progressively higher odds ratio (OR) for CAAC, adjusted for confounders (ORs [95% confidence interval] of 2.34 [0.78 to 7.31], 5.28 [1.56 to 19.5], and 13.6 [2.92 to 74.6] for the second, third, and fourth quartiles, respectively. CONCLUSIONS: The prevalence of CAAC is increased with the decline in the kidney function. FGF23 is independently related to CAAC in patients with CKD who are not on dialysis.

Carotid artery calcification at the initiation of hemodialysis is a risk factor for cardiovascular events in patients with end-stage renal disease: a cohort study.

BACKGROUND: Vascular calcification has been recognized as a risk factor for cardiovascular (CV) events in patients with end-stage renal disease (ESRD). However, the association of carotid artery calcification (CAAC) with CV events remains unknown. The aim of this study was to elucidate whether CAAC is associated with composite CV events in ESRD patients. METHODS: One-hundred thirty-three patients who had been started on hemodialysis between 2004 and 2008 were included in this retrospective cohort study. These patients received multi-detector computed tomography to assess CAAC at the initiation of hemodialysis. Composite CV events, including ischemic heart disease, heart failure, cerebrovascular diseases, and CV deaths after the initiation of hemodialysis, were examined in each patient. RESULTS: CAAC was found in 94 patients (71%). At the end of follow-up, composite CV events were seen in 47 patients: ischemic heart disease in 20, heart failure in 8, cerebrovascular disease in 12, and CV deaths in 7. The incidence of CAAC was 87% in patients with CV events, which was significantly higher than the rate (62%) in those without. Kaplan-Meier analysis showed a significant increase in composite CV events in patients with CAAC compared with those without CAAC (p = 0.001, log-rank test). Univariate analysis using a Cox hazards model showed that age, smoking, common carotid artery intima-media thickness and CAAC were risk factors for composite CV events. In multivariate analysis, only CAAC was a significant risk factor for composite CV events (hazard ratio, 2.85; 95% confidence interval, 1.18-8.00; p = 0.02). CONCLUSIONS: CAAC is an independent risk factor for CV events in ESRD patients. The assessment of CAAC at the initiation of hemodialysis is useful for predicting the prognosis.