CHRONIC CYCLOSPORINE NEPHROTOXICITY IS NOT CLINICALLY RELEVANT IN LONG TERM ALLOGRAFT FUNCTION OR SURVIVAL

Abstract

220 Chronic cyclosporine (CsA) nephrotoxicity remains a major area of concern within the transplant community. Although CsA-associated progressive renal damage clearly occurs in native kidneys of heart and liver transplant patients (pts), similar effects may not occur in the renal allograft. In an attempt to address this question, we obtained serum creatinines (Scr, mg/dl), iothalamate clearances (IoCl, ml/m) and CsA levels (ng/ml) in 110 consecutive renal transplants with a minimum of one year graft survival and 6-9 year followup. Pts were separated into stable (group I, n=80) or declining (group II, n=30) groups based upon the change in serial IoCls over the first post-transplant yr. Biopsies were performed on pts with deteriorating renal function, proteinuria, or graft failure and interpreted by two nephropathologists in a blinded fashion. TableTableIn the 80 pts in Group I there were 8 graft losses; 4 cardiac, 1 cancer and 3 to chronic rejection at 6, 7 and 7 years. Stable and declining pt groups were indistinguishable at 3 months. However, at one year, the declining group demonstrated significantly lower IoCl and higher Scr despite identical CsA levels and doses. These differences persisted in years 2-8. Biopsies were available for review on 28 of 30 pts (Group II). Seven biopsies demonstrated chronic or de-novo glomerulonephritis, 2 had cholesterol emboli and 19 had biopsy proven chronic rejection. No biopsy was interpreted as showing evidence of CsA nephrotoxicity. Twenty-one of 30 grafts in Group II had failed at a mean of 4.8 years. In summary, 70% of renal transplant recipients demonstrated stable IoCl despite maintenance of CsA levels greater than 200 ng/ml for 6-9 yrs. Further, chronic CsA nephrotoxicity was not detected pathologically in the declining group or clinically (stable IoCl despite CsA levels >200 ng/ml) in the stable group over the 6-9 yr follow-up. We conclude that chronic CsA nephrotoxicity may be a cause of declining function or graft loss in renal transplants, but if so, it is exceedingly rare.