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

Abstract

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).

1,25-dihydroxyvitamin-D3 but not the clinically applied marker 25-hydroxyvitamin-D3 predicts survival after stem cell transplantation

“…Zhang et al showed that the beneficial effect of 1,25-dihydroxyvitamin-D3 in rat liver Tx involves the reduction of proinflammatory pathways [34] pointing to an active immunomodulatory role of 1,25-dihydroxyvitamin-D3 in improving the outcome. Consistently, administration of 1,25-dihydroxyvitamin-D3 or an analogon to patients receiving renal Tx was found to reduce the risk of adverse events [31,37]. Patients with unrelated donors versus patients with sibling donors.…”

Vitamin D Deficiency in Renal Disease

“…Cholecalciferol supplementation failed to demonstrate renoprotection in prospective study [88]. However, in a recent prospective placebocontrolled study, paricalcitol ameliorated proteinuria in KTRs [89].…”

First and second morning spot urine protein measurements for the assessment of proteinuria: a diagnostic accuracy study in kidney transplant recipients

“…We performed an investigator-initiated, observational, cross-sectional study of adult deceased donor kidney transplant recipients that completed the ‘Paricalcitol versus placebo for reduction of proteinuria in kidney transplant recipients: a double-blind, randomized controlled trial’ ( ClinicalTrials.gov , number NCT01436747 ) [ 14 ]. Briefly, between July of 2012 and October of 2014 the Paricalcitol trial recruited a national cohort of adult kidney transplant recipients with stages 1–4 chronic kidney disease (CKD) and residual proteinuria more than 3 months after transplant.…”

“…Inclusion criteria were urinary PCR ≥20 mg/mmol despite optimization of the single-agent renin-angiotensin-aldosterone system blockade and an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73m 2 . The study included a 12-week screening phase followed by a 24-week randomized treatment period and an 8-week follow-up after treatment withdrawal [ 14 ].…”

“…To investigate the performance of ePER determined from PCR in the first and second morning urine in different histologic phenotypes of allograft injury, we reanalyzed data restricted to study patients with information on histologic diagnoses of allograft injury from the Paricalcitol trial [ 14 ]. There were 76 patients available for this analysis.…”