TY - JOUR
T1 - Tacrolimus and cyclosporine nephrotoxicity in native kidneys of pancreas transplant recipients
AU - Fioretto, Paola
AU - Najafian, Behzad
AU - Sutherland, David E.R.
AU - Mauer, Michael
PY - 2011/1/1
Y1 - 2011/1/1
N2 - Background and objectives: Calcineurin inhibitors, while representing advances for solid organ transplantation, have nephrotoxic potential that reduces their net benefit. Tacrolimus has been considered less nephrotoxic than cyclosporine, but direct quantitative comparisons of the changes in renal structure from baseline to follow-up biopsies have not been done. To avoid the pitfalls of renal allograft studies, including rejection and disease recurrence, we compared the development of calcineurin lesions in the native kidneys of 14 tacrolimus- and 12 calcineurin-treated pancreas transplant alone recipients cured of type 1 diabetes. Design, setting, participants, & measurements: Research renal biopsies obtained before and at 5 years after transplantation were studied using established morphometric methods. Results: The cyclosporine and tacrolimus groups had, respectively, on average, 33% versus 44% decline in GFR (ns), 27% versus 29% increase in cortical interstitial fractional volume (ns), 245% versus 347% increase in the fractional volume of cortical tubules that were atrophic (ns), and 291% versus 392% increase in the percent of globally sclerotic glomeruli (ns). Arteriolar hyalinosis did not change significantly in either group. Conclusions: These studies indicate that the nephrotoxic potential of tacrolimus and cyclosporine are equivalent and support the development of strategies to reduce these negative effects.
AB - Background and objectives: Calcineurin inhibitors, while representing advances for solid organ transplantation, have nephrotoxic potential that reduces their net benefit. Tacrolimus has been considered less nephrotoxic than cyclosporine, but direct quantitative comparisons of the changes in renal structure from baseline to follow-up biopsies have not been done. To avoid the pitfalls of renal allograft studies, including rejection and disease recurrence, we compared the development of calcineurin lesions in the native kidneys of 14 tacrolimus- and 12 calcineurin-treated pancreas transplant alone recipients cured of type 1 diabetes. Design, setting, participants, & measurements: Research renal biopsies obtained before and at 5 years after transplantation were studied using established morphometric methods. Results: The cyclosporine and tacrolimus groups had, respectively, on average, 33% versus 44% decline in GFR (ns), 27% versus 29% increase in cortical interstitial fractional volume (ns), 245% versus 347% increase in the fractional volume of cortical tubules that were atrophic (ns), and 291% versus 392% increase in the percent of globally sclerotic glomeruli (ns). Arteriolar hyalinosis did not change significantly in either group. Conclusions: These studies indicate that the nephrotoxic potential of tacrolimus and cyclosporine are equivalent and support the development of strategies to reduce these negative effects.
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U2 - 10.2215/CJN.03850510
DO - 10.2215/CJN.03850510
M3 - Article
C2 - 21051744
AN - SCOPUS:79251513317
SN - 1555-9041
VL - 6
SP - 101
EP - 106
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 1
ER -