Effects of paricalcitol on cardiovascular outcomes and renal function in patients with chronic kidney disease. A meta-analysis

Paricalcitol, a selective activator of the vitamin D receptor (VDR), influences calcium and phosphorus homeostasis and bone metabolism. Whether paricalcitol reduces cardiovascular risk and protects renal function remains unclear. To systematically evaluate this in patients with chronic kidney disease (CKD), we conducted a meta-analysis of published randomized controlled trials (RCTs). We searched MEDLINE, Embase, the Cochrane Library, and reference lists for RCTs comparing paricalcitol with placebo in stage 2-5 CKD (including pre-dialysis and renal replacement patients). The Cochrane quality assessment method was used to evaluate study quality. Results were summarized as risk ratios (RRs) for dichotomous outcomes or mean differences (MD) for continuous outcomes. We included 21 studies comprising 1894 patients. Compared to placebo, paricalcitol reduced the risk of cardiovascular events (RR 0.55; 95% CI 0.35-0.87; p = 0.01), but the RR of hypercalcemia associated with paricalcitol was 6.50 (95% CI 3.21-13.15; p < 0.00001). Paricalcitol cannot significantly change systolic blood pressure and cardiac structure. Although proteinuria reduction was achieved more frequently with paricalcitol (RR 1.51; 95% CI 1.25-1.82; p < 0.0001), it did not significantly reduce proteinuria level compared to placebo. Paricalcitol could not protect renal function to delay CKD progression, since it reduced the glomerular filtration rate (MD -3.15; 95% CI -4.35--1.96; p < 0.0001) and elevated serum creatinine (MD 0.93; 95% CI 0.10-0.68; p = 0.008). Paricalcitol reduces the risk of cardiovascular events in CKD patients but increases the risk of hypercalcemia and cannot improve cardiac structure. Meanwhile, it cannot significantly reduce proteinuria level or protect renal function.