AIMS: Paricalcitol, a selective vitamin D activator, decreases proteinuria and may reduce graft failure risk in kidney transplant recipients. In this study, we evaluated the effect of paricalcitol on renin-angiotensin system (RAS) activity as well as interleukin (IL)-6 and transforming growth factor (TGF)-β plasma concentrations as biomarkers of inflammation and fibrosis. METHODS: This placebo-controlled, double-blind trial enrolled a national cohort of kidney transplant recipients with urinary protein-to-creatinine ratio (UPCR) ≥ 20 mg/mmol despite optimization of the RAS blockade. Patients were randomly assigned to receive 24 weeks of treatment with 2 µg/day paricalcitol or placebo. The primary endpoint was the percent change in geometric mean UPCR. In this secondary analysis, we examined the effect of paricalcitol on plasma renin activity (PRA) and aldosterone levels as well as IL-6 and TGF-β plasma concentrations from baseline to last measurement during treatment. RESULTS: Of the 168 patients with UPCR ≥ 20 mg/mmol who consented to undergoing randomization, 83 were allocated toparicalcitol and 85 to placebo. Baseline patient demographics, clinical characteristics, PRA, and aldosterone levels were similar between groups. Mean change in IL-6 was -29% (from 2.53 to 2.02 pg/mL) in the paricalcitol group and 23% (from 2.07 to 2.54 pg/mL) in the placebo group (p < 0.001). Mean change in TGF-β was -12% (from 8,011 to 6,935 pg/mL) in the paricalcitol group and 21% (from 7,418 to 8,992 pg/mL) in the placebo group (p < 0.001). CONCLUSION: In kidney transplant recipients, the addition of 2 µg/day paricalcitol to RAS inhibition lowers IL-6 and TGF-β concentrations, which may be beneficial for reducing graft inflammation and fibrosis. .
RCT Entities:
AIMS: Paricalcitol, a selective vitamin D activator, decreases proteinuria and may reduce graft failure risk in kidney transplant recipients. In this study, we evaluated the effect of paricalcitol on renin-angiotensin system (RAS) activity as well as interleukin (IL)-6 and transforming growth factor (TGF)-β plasma concentrations as biomarkers of inflammation and fibrosis. METHODS: This placebo-controlled, double-blind trial enrolled a national cohort of kidney transplant recipients with urinary protein-to-creatinine ratio (UPCR) ≥ 20 mg/mmol despite optimization of the RAS blockade. Patients were randomly assigned to receive 24 weeks of treatment with 2 µg/day paricalcitol or placebo. The primary endpoint was the percent change in geometric mean UPCR. In this secondary analysis, we examined the effect of paricalcitol on plasma renin activity (PRA) and aldosterone levels as well as IL-6 and TGF-β plasma concentrations from baseline to last measurement during treatment. RESULTS: Of the 168 patients with UPCR ≥ 20 mg/mmol who consented to undergoing randomization, 83 were allocated to paricalcitol and 85 to placebo. Baseline patient demographics, clinical characteristics, PRA, and aldosterone levels were similar between groups. Mean change in IL-6 was -29% (from 2.53 to 2.02 pg/mL) in the paricalcitol group and 23% (from 2.07 to 2.54 pg/mL) in the placebo group (p < 0.001). Mean change in TGF-β was -12% (from 8,011 to 6,935 pg/mL) in the paricalcitol group and 21% (from 7,418 to 8,992 pg/mL) in the placebo group (p < 0.001). CONCLUSION: In kidney transplant recipients, the addition of 2 µg/day paricalcitol to RAS inhibition lowers IL-6 and TGF-β concentrations, which may be beneficial for reducing graft inflammation and fibrosis. .
Authors: Suetonia C Palmer; Edmund Ym Chung; David O McGregor; Friederike Bachmann; Giovanni Fm Strippoli Journal: Cochrane Database Syst Rev Date: 2019-10-22
Authors: Monica L Brown Lobbins; Andrzej T Slominski; Karen A Hasty; Sicheng Zhang; Duane D Miller; Wei Li; Tae-Kang Kim; Zorica Janjetovic; Robert C Tuckey; Imara-Safi O Scott; Linda K Myers; Arnold E Postlethwaite Journal: Int J Mol Sci Date: 2021-12-29 Impact factor: 5.923
Authors: Michał Ciebiera; Marta Włodarczyk; Magdalena Ciebiera; Kornelia Zaręba; Krzysztof Łukaszuk; Grzegorz Jakiel Journal: Int J Mol Sci Date: 2018-07-14 Impact factor: 5.923