HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: CJN.03751106v1 2/2/326    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 Letavernier, E. Articles by Legendre, C. Search for Related Content PubMed PubMed Citation Articles by Letavernier, E. Articles by Legendre, C. Related Collections Related Article

High Sirolimus Levels May Induce Focal Segmental Glomerulosclerosis De Novo

Emmanuel Letavernier^*, Patrick Bruneval, Chantal Mandet, Jean-Paul Duong Van Huyen, Marie-Noëlle Péraldi, Imed Helal^*, Laure-Hélène Noël, and Christophe Legendre^*

^* Service de Transplantation Adulte, Hôpital Necker, Unité INSERM U652, Service de Néphrologie et Transplantation, Hôpital Saint-Louis, and Unité de pathologie rénale INSERM U507, Paris, France

Address correspondence to: Prof. Christophe Legendre, Service de Transplantation Adulte Hôpital Necker, 149 rue de Sèvres 75743 Paris, France, Phone: +33-1-44-49-54-32; Fax: +33-1-44-49-54-30; E-mail: christophe.legendre{at}nck.ap-hop-paris.fr

Sirolimus has been associated with high-range proteinuria when used in replacement of calcineurin inhibitors in renal transplant recipients with chronic allograft nephropathy (CAN). Primary FSGS was demonstrated previously in some such patients, but the coexistence of CAN lesions made the interpretation uneasy. However, nephrotic syndrome and FSGS were observed recently in three patients who received sirolimus de novo, without medical history of primary FSGS or CAN. Markers of podocyte differentiation were studied in kidney biopsies of the three patients who received sirolimus de novo and of five patients who switched to sirolimus. All patients developed FSGS lesions of classic type (not otherwise specified), but only switched patients exhibited advanced sclerotic lesions. Immunohistochemistry showed that some podocytes in FSGS lesions had absent or diminished expression of the podocyte-specific epitopes synaptopodin and p57, reflecting dedifferentiation, and had acquired expression of cytokeratin and PAX2, reflecting a immature fetal phenotype. Such a pattern of epitope expression provides evidence for podocyte dysregulation. Moreover, a decrease in vascular endothelial growth factor expression was observed in some glomeruli. In conclusion, sirolimus induces FSGS that is responsible for proteinuria in some transplant patients.

Related Article

Sirolimus: Defining Nephrotoxicity in the Renal Transplant Recipient

Stephen J. Tomlanovich and Flavio Vincenti
Clin. J. Am. Soc. Nephrol. 2007 2: 198-199. [Full Text] [PDF]

This article has been cited by other articles:

				J. Torras, I. Herrero-Fresneda, O. Gulias, M. Flaquer, A. Vidal, J. M. Cruzado, N. Lloberas, M.{m. d.}l. Franquesa, and J. M. Grinyo Rapamycin has dual opposing effects on proteinuric experimental nephropathies: is it a matter of podocyte damage? Nephrol. Dial. Transplant., August 11, 2009; (2009) gfp367v1. [Abstract] [Full Text] [PDF]

				D. S. Gipson, S. F. Massengill, L. Yao, S. Nagaraj, W. E. Smoyer, J. D. Mahan, D. Wigfall, P. Miles, L. Powell, J.-J. Lin, et al. Management of Childhood Onset Nephrotic Syndrome Pediatrics, August 1, 2009; 124(2): 747 - 757. [Abstract] [Full Text] [PDF]

				M. A. Perazella Renal Vulnerability to Drug Toxicity Clin. J. Am. Soc. Nephrol., July 1, 2009; 4(7): 1275 - 1283. [Abstract] [Full Text] [PDF]

				R John and A M Herzenberg Renal toxicity of therapeutic drugs J. Clin. Pathol., June 1, 2009; 62(6): 505 - 515. [Abstract] [Full Text] [PDF]

				W. Chailimpamontree, S. Dmitrienko, G. Li, R. Balshaw, A. Magil, R. J. Shapiro, D. Landsberg, J. Gill, P. A. Keown, and and the Genome Canada Biomarkers in Transplantatio Probability, Predictors, and Prognosis of Posttransplantation Glomerulonephritis J. Am. Soc. Nephrol., April 1, 2009; 20(4): 843 - 851. [Abstract] [Full Text] [PDF]

				E. Letavernier, P. Bruneval, S. Vandermeersch, J. Perez, C. Mandet, M.-F. Belair, J.-p. Haymann, C. Legendre, and L. Baud Sirolimus interacts with pathways essential for podocyte integrity Nephrol. Dial. Transplant., February 1, 2009; 24(2): 630 - 638. [Abstract] [Full Text] [PDF]

				A. Skoberne, A. Konieczny, and M. Schiffer Glomerular epithelial cells in the urine: what has to be done to make them worthwhile? Am J Physiol Renal Physiol, February 1, 2009; 296(2): F230 - F241. [Abstract] [Full Text] [PDF]

				B. Vollenbroker, B. George, M. Wolfgart, M. A. Saleem, H. Pavenstadt, and T. Weide mTOR regulates expression of slit diaphragm proteins and cytoskeleton structure in podocytes Am J Physiol Renal Physiol, February 1, 2009; 296(2): F418 - F426. [Abstract] [Full Text] [PDF]

				W. A. Golgert, G. B. Appel, and S. Hariharan Recurrent Glomerulonephritis after Renal Transplantation: An Unsolved Problem Clin. J. Am. Soc. Nephrol., May 1, 2008; 3(3): 800 - 807. [Abstract] [Full Text] [PDF]

				M. Nepal, R. Mainali, C. M. Schworer, W. Difilippo, P. L. Zhang, and M. F. Schultz Nephrotic Range Proteinuria: Rare Manifestation of Scleroderma Renal Crisis Ann. Clin. Lab. Sci., January 1, 2008; 38(2): 163 - 167. [Abstract] [Full Text] [PDF]