Cyclosporin exposure correlates with 1 year graft function and histological damage in renal transplanted patients.

Abstract

Cyclosporin (CsA) level obtained 2 h after the morning dose (C(2)) has been shown to accurately predict total CsA exposure and acute rejection (AR) risk, whereas conventional trough levels (C(0)) do not. The impact of C(2) monitoring on long-term kidney graft function, independent from AR risk, is still unclear, however, and it was assessed in the present study. We enrolled 39 CsA-treated renal transplant recipients and used 1 year graft function and histological structure as surrogate markers of graft outcome. CsA dose was adjusted according to C(2) levels. In the first 7 days after grafting, 40-51% of patients failed to reach target C(2) levels; nevertheless, at 1 year the incidence of AR was only 2.5% and graft and patient survival was 100%. The decrease of serum creatinine (12-6 months) was associated with significantly higher C(2) levels over time (P = 0.0003) and lower intrapatient variability of CsA relative absorption (CV) (P = 0.0006). One year graft biopsy showed chronic tubulointerstitial lesions in 54.5% of patients. Both C(2) mean levels and the percentage CV independently predicted the severity of chronic histological lesions (R = 0.69, P<0.0001). Higher C(2) levels, within the proposed target range values, seem to be associated with better renal function and structure.