2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2006091028v1 18/6/1796    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mizobuchi, M. Articles by Slatopolsky, E. Search for Related Content PubMed PubMed Citation Articles by Mizobuchi, M. Articles by Slatopolsky, E. Related Collections Related Article

Combination Therapy with an Angiotensin-Converting Enzyme Inhibitor and a Vitamin D Analog Suppresses the Progression of Renal Insufficiency in Uremic Rats

Masahide Mizobuchi^*,, Jeremiah Morrissey^*,, Jane L. Finch^*, Daniel R. Martin^*, Helen Liapis^*,, Tadao Akizawa and Eduardo Slatopolsky^*

^* Renal Division, Cell Biology and Physiology, and Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri; and Department of Nephrology, Showa University School of Medicine, Tokyo, Japan

Address correspondence to: Dr. Eduardo Slatopolsky, Renal Division, Box 8126, Washington University School of Medicine, St. Louis, MO 63110. Phone: 314-362-7208; Fax: 314-362-7875; E-mail: eslatopo{at}im.wustl.edu

Received for publication September 21, 2006. Accepted for publication March 22, 2007.

Monotherapy with angiotensin-converting enzyme inhibitors has been shown to be beneficial in suppressing the progression of experimentally induced kidney diseases. Whether such therapy provides additional benefits when combined with vitamin D or an analog of vitamin D has not been established. Rats were made uremic by 5/6 nephrectomy and treated as follows: Uremic + vehicle (UC), uremic + enalapril (30 mg/L in drinking water; E), uremic + paricalcitol (19-nor; 0.8 µg/kg, three times a week), and uremic + enalapril + paricalcitol (E + 19-nor). A group of normal rats served as control (NC). BP was significantly elevated in the UC and 19-nor groups compared with the NC group but was indistinguishable from normal in the E and E + 19-nor groups. The decrease in creatinine clearance and the increase in the excretion of urinary protein that were observed in the UC group were ameliorated by the use of E alone or by E + 19-nor (P < 0.05 versus UC). The glomerulosclerotic index was significantly decreased in both the 19-nor (P < 0.01) and E + 19-nor groups (P < 0.01) compared with the UC group. Tubulointerstitial volume was significantly decreased in both the E (P < 0.05) and E + 19-nor groups (P < 0.01) compared with the UC group. Both macrophage infiltration (ED-1–positive cells) and production of the chemokine monocyte chemoattractant protein-1 were significantly blunted in E + 19-nor compared with E group. TGF-1 mRNA and protein expression were increased in the UC group (mRNA: 23.7-fold; protein: 29.1-fold versus NC). These increases were significantly blunted in the 19-nor group (mRNA: 7.1-fold; protein: 8.0-fold versus NC) and virtually normalized in the E + 19-nor group (protein: 0.8-fold versus NC). Phosphorylation of Smad2 was also elevated in the UC group (7.6-fold versus NC) but less so in the 19-nor–treated rats (5.5-fold versus NC). When rats were treated with E + 19-nor, the phosphorylation of Smad2 was normal (1.1-fold versus NC). Thus, 19-nor can suppress the progression of renal insufficiency via mediation of the TGF- signaling pathway, and this effect is amplified when BP is controlled via renin-angiotensin system blockade.

Related Article

This Month's Highlights
J. Am. Soc. Nephrol. 2007 18: 1617-1618. [Full Text] [PDF]

This article has been cited by other articles:

				A. L. Negri Association of oral calcitriol with improved survival in non-dialyzed and dialyzed patients with CKD Nephrol. Dial. Transplant., November 7, 2008; (2008) gfn624v1. [Full Text] [PDF]

				X. Tan, X. Wen, and Y. Liu Paricalcitol Inhibits Renal Inflammation by Promoting Vitamin D Receptor-Mediated Sequestration of NF-{kappa}B Signaling J. Am. Soc. Nephrol., September 1, 2008; 19(9): 1741 - 1752. [Abstract] [Full Text] [PDF]

				M. R. Weir Is Activated Vitamin D Supplementation Renoprotective? Hypertension, August 1, 2008; 52(2): 211 - 212. [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673