Total parathyroidectomy improves survival of hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND AND AIMS: To compare the prognosis of chronic hemodialysis patients with or without parathyroidectomy. METHODS: Among 158 chronic hemodialysis patients who underwent total parathyroidectomy between July 1998 and April 2009, 88 patients were matched with 88 controls for sex, age, underlying disease and prior dialysis history. Then a retrospective evaluation of their prognosis was performed over a median observation period of 4.41 years. RESULTS: The overall survival rate was 90.4% in the parathyroidectomy group and 67.4% in the control group. The cardiovascular death-free survival rate was 94.6% in the parathyroidectomy group and 76.3% in the control group. During observation, intact parathyroid hormone was measured every 6 months, and its average serum level was 37 ± 92 ng/L in the total parathyroidectomy group versus 274 ± 233 ng/L in the control group (p=0.0001). The total parathyroidectomy group had a significantly lower corrected calcium level and higher serum albumin level. Multivariate analysis revealed that parathyroidectomy, atrial fibrillation and serum albumin were significant factors for both total and cardiovascular mortality. CONCLUSION: Total parathyroidectomy was associated with better survival, probably due to decreased cardiovascular mortality.

Oral nicorandil for prevention of cardiac death in hemodialysis patients without obstructive coronary artery disease: a propensity-matched patient analysis.

BACKGROUND/AIMS: We examined the potential of oral administration of nicorandil for protecting against cardiac death in hemodialysis patients without obstructive coronary artery disease. METHODS: This study was based on a cohort study of 155 hemodialysis patients with angiographic absence of obstructive coronary lesions, with analysis performed in 100 propensity-matched patients (54 men and 46 women, 64 ± 10 years), including 50 who received oral administration of nicorandil (15 mg/day, nicorandil group) and 50 who did not (control). The efficacy of nicorandil in preventing cardiac death was investigated. RESULTS: Over a mean follow-up period of 5.3 ± 1.9 years, we observed 25 cardiac deaths among 100 propensity-matched patients, including 6 due to acute myocardial infarction, 11 due to heart failure, and 8 due to sudden cardiac death. The incidence of cardiac death was lower (p < 0.001) in the nicorandil group (4/50, 8%) than in the control (21/50, 42%). On multivariate Cox hazard analysis, cardiac death was inversely associated with oral nicorandil (hazard ratio, 0.123; p = 0.0002). On Kaplan-Meier analysis, cardiac death-free survival rates at 5 years were higher in the nicorandil group than in the control group (91.4 vs. 66.4%). CONCLUSION: Oral nicorandil may inhibit cardiac death of hemodialysis patients without obstructive coronary artery disease.

Plasma S100A12 level is associated with cardiovascular disease in hemodialysis patients.

BACKGROUND AND OBJECTIVES: S100A12 is an endogenous receptor ligand for advanced glycation end products. Cardiovascular disease remains a major cause of morbidity and mortality in patients with chronic kidney disease. In this study, we report cross-sectional data on 550 hemodialysis patients and assess the relationship between plasma S100A12 level and cardiovascular disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A cross-sectional study of 550 maintenance hemodialysis patients was conducted. We investigated the past history of cardiovascular disease and quantified the plasma level of S100A12 protein in all participants. RESULTS: Plasma S100A12 level was higher in hemodialysis patients with cardiovascular disease (n=197; 33.8 ± 28.1 ng/ml) than in those without it (n=353; 20.2 ± 16.1 ng/ml; P<0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.13 to 1.44; P<0.001) was identified as an independent factor associated with the prevalence of cardiovascular disease. The other factors associated with the prevalence of cardiovascular diseases were the presence of diabetes mellitus (OR, 2.81; 95% CI, 1.79 to 4.41; P < 0.001) and high-sensitivity CRP level (OR, 1.02; 95% CI, 1.00 to 1.05; P=0.046). Furthermore, the plasma S100A12 level (OR, 1.30; 95% CI, 1.09 to 1.54; P=0.004) was significantly associated with cardiovascular disease even in hemodialysis patients without diabetes mellitus (n=348). CONCLUSIONS: These results suggest that the plasma S100A12 protein level is strongly associated with the prevalence of cardiovascular disease in hemodialysis patients.

Peritoneal mesothelial cells as a target of local aldosterone action: upregulation of connective tissue growth factor expression via serum- and glucocorticoid-inducible protein kinase 1.

BACKGROUND/AIMS: Peritoneal fibrosis can lead to the discontinuation of continuous ambulatory peritoneal dialysis. The present study investigated the direct effect of aldosterone, which influences tissue fibrosis, and its cellular mechanism using cultured rat peritoneal mesothelial cells (RPMCs). MATERIALS AND METHODS: The expression of aldosterone synthase (CYP11B2), mineralocorticoid receptors, 11beta-hydroxysteroid dehydrogenase 2, serum- and glucocorticoid-inducible protein kinase 1 (SGK1) and connective tissue growth factor (CTGF) was evaluated using reverse transcriptase-polymerase chain reaction and Western blot. The ability of RPMCs to produce aldosterone was examined by enzyme immunoassay. Small interfering RNA of SGK1 was transfected to determine the role of SGK1. RESULTS: CYP11B2, mineralocorticoid receptors and 11beta-hydroxysteroid dehydrogenase 2 were expressed in RPMCs. The release of aldosterone from RPMCs into the culture medium was confirmed. Stimulation of RPMCs with the addition of aldosterone significantly increased SGK1 expression and phosphorylation and CTGF upregulation, and these effects were completely inhibited by the mineralocorticoid receptor antagonist spironolactone. SGK1 gene silencing abrogated aldosterone-induced CTGF expression. CONCLUSION: The local aldosterone system exists and acts directly as a profibrotic factor in the peritoneal mesothelium.