Cyclosporine-to-tacrolimus conversion compared with cyclosporine minimization on allograft function and TGF-β1/HGF levels in chronic renal allograft nephropathy

Abstract

Background. Tacrolimus and cyclosporine might have different effects onintra-renal fibrosis and allograft function in chronic renal allograftnephropathy (CAN). It is difficult to predict the response to calcineurininhibitor minimization in patients with CAN.Methods. This prospective randomized study compared cyclosporine A(CsA)-to-tacrolimus conversion (Group A, target tacrolimus trough level6-8 ng/mL) versus CsA minimization (Group B, target CsA trough level 80-100 ng/mL) with regard to efficacy, safety, and effect on growth factorlevels in patients with CAN and deteriorating allograft function. Theprimary efficacy endpoint was improvement in the slope of inverse serumcreatinine (sCr)-against-time plot. Circulating levels of TGF-β1, HGF,BMP-7, VEGF and fibronectin were measured serially in 16 patients.Results. 34 patients were included. 9 (56.3%) subjects in Group A (n=16)and 10 (55.6%) in Group B (n=18) reached the primary endpoint (P=0.968).Group A showed significantly improved 1/sCr-against-time slope followingintervention (P=0.029), while between-group difference was insignificantbefore and after intervention. 9 of 16 patients (56.3%) showed ≥50%TGF-β1 reduction or HGF increase after intervention, amongst whom 8(88.9%) also showed an improvement in 1/sCr-against-time slope. Acuterejection occurred in 2 patients (Group A). Blood glucose, lipids, and bloodpressure did not change significantly, and did not differ between groups.Conclusions. In patients with CAN CsA-to-tacrolimus conversion and CsAminimization targeting low blood levels are both effective in reducing therate of renal function deterioration in over half of the patients, and thisrenal preservation response is accompanied by improvements in TGF-β1and/or HGF.