Paricalcitol versus placebo for reduction of proteinuria in kidney transplant recipients: a double‐blind, randomized controlled trial

Summary Proteinuria after kidney transplantation is accompanied by an increased risk of graft failure. In this single‐center, placebo‐controlled, double‐blind trial we studied whether vitamin D receptor activator paricalcitol might reduce proteinuria. Patients with urinary protein‐to‐creatinine ratio (UPCR) ≥20 mg/mmol despite optimization of the renin angiotensin aldosterone system (RAAS) blockade were randomly assigned to receive 24 weeks’ treatment with 2 μg/day paricalcitol or placebo. Primary endpoint was change in UPCR, and main secondary endpoints were change in urinary albumin‐to‐creatinine ratio (UACR) and 24‐h proteinuria. Analysis was by intention to treat. One hundred and sixty‐eight patients undergo randomization, and 83 were allocated to paricalcitol, and 85 to placebo. Compared with baseline, UPCR declined in the paricalcitol group (−39%, 95% CI −45 to −31) but not in the placebo group (21%, 95% CI 9 to 35), with a between group difference of −49% (95% CI −57 to −41; P  <   0.001). UACR and 24‐h proteinuria decreased only on paricalcitol therapy and significantly differed between groups at end‐of‐treatment ( P  <   0.001). Paricalcitol was well tolerated but incidence of mild hypercalcemia was higher than in placebo. In conclusion, addition of 2 μg/day paricalcitol lowers residual proteinuria in kidney transplant recipients. Long‐term studies are needed to determine if the reduction in proteinuria improves transplant outcomes (ClinicalTrials.gov, number NCT01436747).