CYCLOSPORINE-ASSOCIATED LESIONS IN NATIVE KIDNEYS OF DIABETIC PANCREAS TRANSPLANT RECIPIENTS

Five years of normoglycemia following pancreas transplantation (PT) do es not ameliorate glomerular lesions in patients with their own kidney s and with long-term insulin-dependent diabetes (IDDM) (Lancet 342:119 3, 1993). All these patients received cyclosporine (CsA) as part of th eir immunosuppression. Here we examined the relationship of CsA dose a nd blood levels to the presence and severity of CsA-associated renal l esions and changes in renal function in these PT patients. Renal biops ies were taken before (0) and two and five years after PT from 13 non- uremic IDDM patients and were compared with baseline and five year bio psies from 10 IDDM controls (C). CsA dose was reduced from 10 +/- 3 mg /kg/day in the first month to 5 +/- 2 in the fifth year post-PT. Creat inine clearance (C-Cr) decreased by 34% at one year post-PT and was st able thereafter, and did not change in C. The decline in C-Cr from 0 t o one year was related to CsA blood levels and dose (P < 0.005) at one year. Cortical interstitial volume fraction [Vv(Int/Cortex)], the ind ex of tubular atrophy, and % sclerotic glomeruli increased significant ly from 0 to five years post-PT (P < 0.005, 0.01 and 0.001, respective ly), but did not change in C. There was no significant change from 0 t o two years post-PT in these lesions, while there was a clear progress ion from two to five years. Mean CsA dose and blood levels in the firs t year post-PT correlated with the increase (Delta) in Vv(Int/Cortex) at five years (P < 0.05 for both). The best predictor of Delta Vv(Int/ Cortex) was the change in C-Cr over the first year post-PT (P < 0.003) . In conclusion, in five years serious tubulointerstitial and glomerul osclerotic lesions developed in PT recipients on CsA therapy, but not in IDDM C. These lesions were best predicted by the decline in C-Cr an d CsA blood levels and dose during the first year post-PT. Despite ear ly CsA dose reductions, and stabilization of C-Cr, structural lesions progressed from two to five years post-PT.