Effects of calcitriol and paricalcitol on renal fibrosis in CKD.

Abstract

BACKGROUND\nIn chronic kidney Disease (CKD) the activation of the renin-angiotensin-aldosterone system and renal inflammation stimulate renal fibrosis and the progression to end-stage renal disease. The low levels of vitamin D receptor (VDR) and its activators (VDRAs) contribute to worsen secondary hyperparathyroidism and renal fibrosis.\n\n\nMETHODS\nThe 7/8 nephrectomy model of experimental chronic renal failure (CRF) was used to examine the antifibrotic effects of treatment with two VDRAs (paricalcitol and calcitriol at equivalent doses (3/1 dose ratio) during 4\u2009weeks.\n\n\nRESULTS\nCRF increased the activation of the renin-angiotensin-aldosterone system, renal inflammation and interstitial fibrosis. Paricalcitol treatment reduced renal collagen I and renal interstitial fibrosis by decreasing the activation of the renin-angiotensin-aldosterone system through renal changes in renin, ATR1 and ATR2 mRNAs levels and renal inflammation by decreasing renal inflammatory leukocytes (CD45), ADAM17 mRNA, TGF-β mRNA and protein and maintaining E-cadherin mRNA levels. Calcitriol showed similar trends without significant changes in most of these biomarkers.\n\n\nCONCLUSIONS\nParicalcitol effectively attenuated the renal interstitial fibrosis induced by CRF through a combination of inhibitory actions on the renin-angiotensin-aldosterone system, inflammation and epithelial/mesenchymal transition.