Paricalcitol and endothelial function in chronic kidney disease trial.

Altered vitamin D metabolism and low levels of the active form of this vitamin, 1,25-dihydroxy-vitamin D, is a hallmark of chronic kidney disease (CKD), but there is still no randomized controlled trial testing the effect of active forms of vitamin D on vascular function in patients with CKD. Paricalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY) is a double-blinded randomized controlled trial (ClinicalTrials.gov, NCT01680198) testing the effect of an active form of vitamin D, paricalcitol (2 µg/d×12 weeks) on endothelium-dependent and endothelium-independent vasodilatation in 88 patients with stage 3 to 4 CKD and parathormone >65 pg/mL (paricalcitol, n=44; placebo, n=44). Paricalcitol treatment reduced parathormone (-75 pg/mL; 95% confidence interval, -90 to -60), whereas parathormone showed a small rise during placebo (21 pg/mL; 95% confidence interval, 5-36). Blood pressure did not change in both study arms. Baseline flow-mediated dilation was identical in patients on paricalcitol (3.6±2.9%) and placebo (3.6±2.9%) groups. After 12 weeks of treatment, flow-mediated dilation rose in the paricalcitol but not in the placebo group, and the between-group difference in flow-mediated dilation changes (the primary end point, 1.8%; 95% confidence interval, 0.3-3.1%) was significant (P=0.016), and the mean proportional change in flow-mediated dilation was 61% higher in paricalcitol-treated patients than in placebo-treated patients. Such an effect was abolished 2 weeks after stopping the treatment. No effect of paricalcitol on endothelium-independent vasodilatation was registered. Paricalcitol improves endothelium-dependent vasodilatation in patients with stage 3 to 4 CKD. Findings in this study support the hypothesis that vitamin D may exert favorable effects on the cardiovascular system in patients with CKD.

Ultrafiltration intensification in hemodialysis patients improves hypertension but increases AV fistula complications and cardiovascular events.

INTRODUCTION: Hypertension remains a major problem in hemodialysis (HD) patients. METHODS: We performed a pragmatic trial (Pragmatic Clinical Intervention on Blood Pressure Driven by Audit [CLINIDEA]) testing the effectiveness and safety of a 6-month multimodal intervention in hypertensive HD patients regarding the application of higher ultrafiltration (UF) rates or longer or more frequent dialyses in UF-intolerant patients, and an educational intervention to encourage patients to lower their salt and fluid intake. RESULTS: Blood pressure (BP) in hypertensive patients (n=32) fell from 156.8 ± 13.3 / 81.1 ± 8.9 mm Hg to 147.9 ± 18.8 / 77.5 ± 11.1 mm Hg. UF intensification was well tolerated, and the BP goal was achieved without resorting to longer or more frequent dialyses. BP changes were paralleled by a consistent (p<0.01) fall in dry body weight. The trial largely failed at increasing compliance with salt prescription (salt intake: baseline: 156.9 ± 64 mEq/day, 6-month: 150.7 ± 60.3 mEq/day). During the 12 months preceding the trial, the hospitalization rates for arteriovenous (AV) fistula complications and cardiovascular (CV) events were identical in hypertensive and in normotensive patients. However, these complications selectively increased (AV complications: relative risk [RR] = 7.6; CV complication: RR=8.4) in hypertensive patients coinciding with UF intensification during the trial. Increasing the UF rate is an effective BP-lowering intervention in HD patients. However, this intervention is associated with a higher risk for AV complications and CV events. CONCLUSION: Longer and/or more frequent dialyses and better efforts to increase compliance to low salt diets than those put in place in this study are needed to reduce the high prevalence of hypertension in the HD population.