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) Erratum (v16,p1150) All Versions of this Article: ASN.2003100861v1 16/2/398    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 Erkan, E. Articles by Devarajan, P. Search for Related Content PubMed PubMed Citation Articles by Erkan, E. Articles by Devarajan, P.

Induction of Renal Tubular Cell Apoptosis in Focal Segmental Glomerulosclerosis: Roles of Proteinuria and Fas-Dependent Pathways

Elif Erkan^*,, Clotilde D. Garcia^*,, Larry T. Patterson, Jaya Mishra, Mark M. Mitsnefes, Frederick J. Kaskel^* and Prasad Devarajan^*,

^* Department of Nephrology, Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York; Golisano Children’s Hospital, University of Rochester, Rochester, New York; Department of Pediatric Nephrology, Santa Casa Hospital, Porto Allegre, Brazil; and Department of Nephrology & Hypertension, Cincinnati Children’s Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio

Address correspondence to: Dr. Prasad Devarajan, Nephrology & Hypertension, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039. Phone: 513-636-4531; Fax: 513-636-7404; E-mail: prasad.devarajan{at}cchmc.org

The hypothesis that apoptosis represents a proximate mechanism by which tubule cells are damaged in FSGS was tested. Thirty kidney biopsy specimens from children with idiopathic early FSGS were studied retrospectively. Unexpected, apoptosis was evident in both proximal and distal tubule cells. There was a significant correlation between the degree of proteinuria and the number of apoptotic cells. Fas protein was detected predominantly in the tubule cells that underwent apoptosis. When compared with patients with other chronic proteinuric states, those with FSGS displayed a proliferation/apoptosis ratio in favor of proliferation in the glomerulus but dramatically in favor of apoptosis in the tubules. When both proteinuria and apoptosis were included in a stepwise logistic regression procedure, only apoptosis was found to predict independently the development of ESRD. Prolonged incubation of cultured Madin-Darby canine kidney (distal/collecting) cells with albumin also resulted in a dose- and duration-dependent induction of apoptosis and activation of the Fas pathway, lending support to the novel finding of distal tubule cell apoptosis in patients with FSGS. The results indicate that an elevated tubule cell apoptosis rate at the time of initial biopsy represents an independent predictor of progression to ESRD in patients with early FSGS.

This article has been cited by other articles:

				Y. Urahama, Y. Ohsaki, Y. Fujita, S. Maruyama, Y. Yuzawa, S. Matsuo, and T. Fujimoto Lipid Droplet-Associated Proteins Protect Renal Tubular Cells from Fatty Acid-Induced Apoptosis Am. J. Pathol., November 1, 2008; 173(5): 1286 - 1294. [Abstract] [Full Text] [PDF]

				W. A. Altemeier, X. Zhu, W. R. Berrington, J. M. Harlan, and W. C. Liles Fas (CD95) induces macrophage proinflammatory chemokine production via a MyD88-dependent, caspase-independent pathway J. Leukoc. Biol., September 1, 2007; 82(3): 721 - 728. [Abstract] [Full Text] [PDF]

				F. Theilig, W. Kriz, T. Jerichow, P. Schrade, B. Hahnel, T. Willnow, M. Le Hir, and S. Bachmann Abrogation of Protein Uptake through Megalin-Deficient Proximal Tubules Does Not Safeguard against Tubulointerstitial Injury J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1824 - 1834. [Abstract] [Full Text] [PDF]

				E. Erkan, P. Devarajan, and G. J. Schwartz Mitochondria Are the Major Targets in Albumin-Induced Apoptosis in Proximal Tubule Cells J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1199 - 1208. [Abstract] [Full Text] [PDF]

				M. Abbate, C. Zoja, and G. Remuzzi How Does Proteinuria Cause Progressive Renal Damage? J. Am. Soc. Nephrol., November 1, 2006; 17(11): 2974 - 2984. [Abstract] [Full Text] [PDF]

				M. J. Ross, S. Martinka, V. D. D'Agati, and L. A. Bruggeman NF-{kappa}B Regulates Fas-Mediated Apoptosis in HIV-Associated Nephropathy J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2403 - 2411. [Abstract] [Full Text] [PDF]

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