High sirolimus levels may induce focal segmental glomerulosclerosis de novo
| Autor: | Laure-Hélène Noël, Marie-Noëlle Peraldi, Imed Helal, Emmanuel Letavernier, Chantal Mandet, Christophe Legendre, Patrick Bruneval, Jean-Paul Duong Van Huyen |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Epidemiology Biopsy urologic and male genital diseases Critical Care and Intensive Care Medicine Focal segmental glomerulosclerosis Postoperative Complications Chronic allograft nephropathy medicine Humans Kidney transplantation Sirolimus Transplantation urogenital system business.industry Glomerulosclerosis Focal Segmental Glomerulosclerosis Middle Aged medicine.disease Kidney Transplantation female genital diseases and pregnancy complications Calcineurin surgical procedures operative Nephrology Immunology Synaptopodin Female business Nephrotic syndrome Immunosuppressive Agents medicine.drug |
| Zdroj: | Clinical journal of the American Society of Nephrology : CJASN. 2(2) |
| ISSN: | 1555-905X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|