Early introduction of oral paricalcitol in renal transplant recipients. An open-label randomized study

Abstract

In stable renal transplant recipients with hyperparathyroidism, previous studies have indicated that vitamin D agonist treatment might have anti-proteinuric effects. Animal studies indicate possible anti-fibrotic and anti-inflammatory effects. Early introduction of paricalcitol in de novo renal transplant recipients might reduce proteinuria and prevent progressive allograft fibrosis. We performed a single-center, prospective, randomized, open-label trial investigating effects of paricalcitol 2 μg/day added to standard care. Participants were included 8 weeks after engraftment and followed for 44 weeks. Primary end point was change in spot urine albumin/creatinine ratio. Exploratory microarray analyses of kidney biopsies at study end investigated potential effects on gene expression. Secondary end points included change in glomerular filtration rate (GFR), pulse wave velocity (PWV), and endothelial function measured by peripheral arterial tonometry as reactive hyperemia index (RHI). Seventy-seven de novo transplanted kidney allograft recipients were included, 37 receiving paricalcitol. Paricalcitol treatment lowered PTH levels (P = 0.01) but did not significantly reduce albuminuria (P = 0.76), change vascular parameters (PWV; P = 0.98, RHI; P = 0.33), or influence GFR (P = 0.57). Allograft gene expression was not influenced. To summarize, in newly transplanted renal allograft recipients, paricalcitol reduced PTH and was well tolerated without negatively affecting kidney function. Paricalcitol did not significantly reduce/prevent albuminuria, improve parameters of vascular health, or influence allograft gene expression.

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

“…Only a few patients did not tolerate an ACE inhibitor or ARB where treatment withdrawal was indicated, most commonly due to transplant renal artery stenosis . This is at variance with previous studies where <50% of transplanted patents were treated with RAAS inhibitors . Furthermore, the majority of our patients had moderately decreased kidney function and were on regular sodium diet.…”

“…By contrast, a recent study from Pihlstrøm et al . could not demonstrate a significant reduction of albuminuria or modified allograft expression of genes related to fibrosis and inflammation by paricalcitol in de‐novo transplant recipients. There are several explanations for these seemingly discordant results.…”

“…As pointed out by Pihlstrøm et al . , the complexity of what may occur to kidney grafts early after transplant (e.g., delayed graft function, acute rejection) combined with low levels of albuminuria is likely to mask potential antiproteinuric effects of paricalcitol.…”

Vitamin D as a risk factor for patient survival after kidney transplantation: A prospective observational cohort study

“…Downregulation of the inflammatory response may also explain the association between vitamin D levels in kidney transplant patients and the risk for interstitial fibrosis, graft failure, and death. Another intervention study with paricalcitol post‐transplant found a reduction in PTH but not in vascular health, or influence on allograft gene expression …”

Hyperparathyroidism after renal transplantation

“…Paricalcitol prescription has not negative effects on kidney function (10). It decreases intact PTH and increases bone mineral density in recently transplanted kidney recipients (11).…”