Tacrolimus and cyclosporine nephrotoxicity in native kidneys of pancreas transplant recipients.
OBJECTIVE
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.


METHODS
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.
Department of Medical and Surgical Sciences, University of Padova Medical School, Padova, Italy. paola.fioretto@unipd.it
Paola
P
Fioretto
Behzad
B
Najafian
David E R
DE
Sutherland
Michael
M
Mauer
D000328:Adult; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000009:adverse effects* / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D016559:Tacrolimus / Q000009:adverse effects* / Q000097:blood
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus