Comparison of Tacrolimus and Cyclosporine Nephrotoxicity in Native Kidneys of Diabetic Pancreas Transplant Recipients
B Najafian, P Fioretto, D Sutherland, M Mauer. University of Minnesota, Minneapolis, MN; University of Padova, Padova, Italy; University of Minnesota, Minneapolis
Background: Nephrotoxicity is a major adverse effect of tacrolimus (TAC) and cyclosporine (CSA), two important calcineurin inhibitors (CNI). Severe CSA-associated renal lesions develops within 5 years in pancreas transplanted (PT) patients. However, there is little information on TAC-induced lesions in native kidneys. We evaluated renal structure and function in formerly type 1 diabetic subjects with successful PT treated with TAC or CSA.
Design: Protocol kidney biopsies before and 5 years after PT in 14 patients receiving TAC and 12 patient receiving CSA were compared for interstitial volume fraction [Vv(Int/cortex)], % sclerosed glomeruli (SG), and index of arteriolar hyalinosis (IAH) on PAS stained slides. Glomerular filtration rate (GFR), blood pressure, TAC and CSA dose and blood levels were repeatedly monitored. Patients were on CSA or TAC for at least 4 years.
Results: TAC and CSA groups were comparable for all baseline clinical features and LM parameters except for age, being higher in TAC. GFR decline from baseline to 5 years was not statistically different for TAC (44%) and CSA (33%). Vv(Int/cortex) increased 24% (p<0.001) at 5 years post-PT in TAC and 26% (p<0.005) at 5 years in CSA patients. %SG increased from 6.1±7.5 % at baseline to 30±17.2 % at 5 years (p<0.0001) in TAC, and from 9.1±10.6% to 35.6±19.3 %, in CSA group (p<0.002). IAH did not significantly change in either the TAC or CSA group from baseline to 5 years. Baseline to 5 year changes of Vv(Int/cortex), %SG and IAH were not statistically different between TAC and CSA patients. There were significant inverse correlation between the decrease in GFR and the increase in Vv(Int/cortex) (r=0.68, p=0.005) in TAC group. There was no correlation between any of the TAC dose and blood levels and changes in renal structural and functional parameters, but CSA dose and blood levels in the first post-PT year were significantly correlated with GFR decline and Vv(Int/cortex) increase from baseline to 5 year follow-up.
Conclusions: This study demonstrates that in type 1 diabetic native kidney successful pancreas transplant recipients, the chronic nephrotoxic effects of TAC are similar to those of CSA both in terms of renal function and of renal structure. Alternative immunosuppression strategies could improve the risk to benefit ratio of PTA.
Category: Kidney (does not include tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 232, Wednesday Afternoon