tacrolimus and Tyrosinemias

Cyclosporine A (CyA) and tacrolimus are the principal immunosuppressive agents used for OLT in children. However, progressive deterioration of renal function from calcineurin inhibitor toxicity after OLT has been widely reported. The aim of this study was to assess long-term renal function in children after OLT.. We reviewed all OLT patients surviving >1 year at Sainte Justine Hospital from 1987 to 2003. The GFR (ml/min/1.73 m) was measured yearly by the Tc-99m DTPA single injection technique. In all, 101 OLT patients (27 tyrosinemia, 33 biliary atresia, 5 fulminant hepatic failure, 36 miscellaneous) were studied. Median age at OLT was 35 months (range 6-178 months) in tyrosinemia group and 58 months (range 1-226 months) in the "Others" (P = NS), median pediatric end-stage liver disease score was respectively 3 (range -9 to 21) and 15 (-9 to 35), (P=0.001), and median follow-up was 6 (range 1-14) and 6 (range 1-17) (P = NS) years, respectively. Median annual GFR values in tyrosinemia fluctuated between 61 and 104 ml/min/1.73 m, with an improving tendency, and 94-121 ml/min/1.73 m in the Others. GFR did not differ on CyA vs. tacrolimus treatment. The median duration of therapy with calcium-channel blocker in the tyrosinemia group was 5 (1-13) vs. 2 (1-13) years in the Others.. Median GFR remained normal in most nontyrosinemia patients (Others). Tyrosinemia patients remained stable at a lower GFR. CyA administration in three daily doses and prolonged calcium-channel blocker therapy may have contributed to this stability. Impairment of kidney function was associated with congenital kidney disease, toxic kidney injury, and portal hypertension.

Topics: Adolescent; Calcineurin Inhibitors; Calcium Channel Blockers; Child; Child, Preschool; Cyclosporine; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Immunosuppressive Agents; Infant; Kidney; Liver Transplantation; Male; Tacrolimus; Tyrosinemias