Exploring the potential effect of paricalcitol on markers of inflammation in de novo renal transplant recipients.

Following a successful renal transplantation circulating markers of inflammation may remain elevated, and systemic inflammation is associated with worse clinical outcome in renal transplant recipients (RTRs). Vitamin D-receptor (VDR) activation is postulated to modulate inflammation and endothelial function. We aimed to explore if a synthetic vitamin D, paricalcitol, could influence systemic inflammation and immune activation in RTRs. Newly transplanted RTRs were included in an open-label randomized controlled trial on the effect of paricalcitol on top of standard care over the first post-transplant year. Fourteen pre-defined circulating biomarkers reflecting leukocyte activation, endothelial activation, fibrosis and general inflammatory burden were analyzed in 74 RTRs at 8 weeks (baseline) and 1 year post-engraftment. Mean changes in plasma biomarker concentrations were compared by t-test. The expression of genes coding for the same biomarkers were investigated in 1-year surveillance graft biopsies (n = 60). In patients treated with paricalcitol circulating osteoprotegerin levels increased by 0.19 ng/ml, compared with a 0.05 ng/ml increase in controls (p = 0.030). In graft tissue, a 21% higher median gene expression level of TNFRSF11B coding for osteoprotegerin was found in paricalcitol-treated patients compared with controls (p = 0.026). Paricalcitol treatment did not significantly affect the blood- or tissue levels of any other investigated inflammatory marker. In RTRs, paricalcitol treatment might increase both circulating and tissue levels of osteoprotegerin, a modulator of calcification, but potential anti-inflammatory treatment effects in RTRs are likely very modest. [NCT01694160 (2012/107D)]; [www.clinicaltrials.gov].

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

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.