http://cjasn.asnjournals.org Clinical Journal of the American Society of Nephrology RSS feed -- recent Transplantation articles 1555-905X Clinical Journal of the American Society of Nephrology 1555-9041 http://cjasn.asnjournals.org/icons/banner/title.gif http://cjasn.asnjournals.org http://cjasn.asnjournals.org/cgi/content/short/2/2/326?rss=1 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.

]]> 2007-02-27 info:doi/10.2215/CJN.03751106 American Society of Nephrology 2 2 333 2007-03-01 326 Transplantation http://cjasn.asnjournals.org/cgi/content/short/2/1/135?rss=1 Calcineurin inhibitor toxicity (CNIT) is an important cause of chronic allograft nephropathy (CAN), but clinically relevant, diagnostic pathologic criteria remain to be defined. A semiquantitative, clinically correlative CNIT scoring system was developed and validated by pathologic analyses of 254 renal transplant biopsies that were obtained from 50 consecutive pediatric renal transplant recipients. Differentially weighted pathologic criteria (glomerulosclerosis, tubular atrophy, arteriolar medial hyaline, and tubular isometric vacuolization) contributed to the composite CNIT model score. Unlike other established pathology chronicity scores, such as the chronic allograft damage index, Banff, and modified Banff, the CNIT score was highly correlated with future graft function. The 3-mo CNIT score correlated significantly with 12 mo (P = 0.021) and 24 mo (P = 0.03) calculated creatinine clearance. Arteriolar medial hyalinosis seems to be the most important factor contributing to the clinical impact of the CNIT score.

]]> 2006-12-29 info:doi/10.2215/CJN.01320406 American Society of Nephrology 1 2 142 2007-01-01 135 Transplantation