Antiproteinuric effect of oral paricalcitol in chronic kidney disease

Rajiv Agarwal, Muralidhar Acharya, Jin Tian, Richard L. Hippensteel, Joel Z. Melnick, Ping Qiu, Laura Williams, Daniel Batlle

Research output: Contribution to journalArticle

313 Scopus citations

Abstract

Background. Proteinuria is a marker of cardiovascular and renal disease in patients with chronic kidney disease (CKD), and reduction in proteinuria has been associated with improved cardiovascular and renal outcomes. While active vitamin D and its analogs have been shown to have renal protective effects in animals, these hormones have not been shown to reduce proteinuria in CKD patients. Methods. In three double-blind, randomized, placebo-controlled studies to evaluate the safety and efficacy of oral paricalcitol, 220 CKD stage 3 and 4 patients with secondary hyperparathyroidism (SHPT) were randomized to oral paricalcitol (N = 107, mean dose 9.5 μg/week) or placebo (N = 113) and followed for up to 24 weeks. In conjunction with other safety measures, proteinuria was measured by dipstick and read by an automated reader at the beginning and end of trial. We subsequently analyzed the dipstick data to evaluate the effect of paricalcitol on proteinuria. Results. At baseline, proteinuria was present in 57 patients randomized to oral paricalcitol and 61patients randomized to placebo (NS). At the final visit, 29/57 (51%) of the paricalcitol patients compared to 15/61 (25%) placebo patients had reduction in proteinuria, P = 0.004 (odds for reduction in proteinuria 3.2 times greater for paricalcitol patients, 95% CI 1.5-6.9). For the patients who had both proteinuria at baseline and parathyroid hormone (PTH) suppression (end point defined as 2 consecutive >30% decreases in iPTH from baseline), 27/51 (53%) patients had a reduction in the proteinuria in the paricalcitol group and 0/7 (0%) had a reduction in proteinuria in the placebo group. Reduction of proteinuria favored patients on paricalcitol, regardless of age, sex, race, diabetes mellitus, hypertension, or use of therapies to block the renin-angiotensin-aldosterone system (RAAS). Conclusion. Our results demonstrate that the reduction in proteinuria was associated with paricalcitol treatment, and the reduction in proteinuria was independent of concomitant use of agents that block the RAAS. Paricalcitol as a potential pharmacologic means of reducing proteinuria in CKD patients warrants further investigation.

Original languageEnglish (US)
Pages (from-to)2823-2828
Number of pages6
JournalKidney international
Volume68
Issue number6
DOIs
StatePublished - Dec 1 2005
Externally publishedYes

Keywords

  • Chronic kidney disease
  • Paricalcitol
  • Proteinuria
  • Vitamin D

ASJC Scopus subject areas

  • Nephrology

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    Agarwal, R., Acharya, M., Tian, J., Hippensteel, R. L., Melnick, J. Z., Qiu, P., Williams, L., & Batlle, D. (2005). Antiproteinuric effect of oral paricalcitol in chronic kidney disease. Kidney international, 68(6), 2823-2828. https://doi.org/10.1111/j.1523-1755.2005.00755.x