EFFECT OF CYCLOSPORIN ON GLOMERULAR AND TUBULAR RENAL FUNCTION IN CHILDREN WITH LIVER TRANSPLANTATION

Abstract

36 Cyclosporin seems to have a nephrotoxicity reversibly in the short term and more permanently in the long term. The aim of this study is to determine retrospectively both tubular and glomerular function in the pediatric liver recipients in our institution. 28 patients (13 boys, 15 girls; age at transplantation : 4.0±3.6 yrs; weight : 14.4 kg±2.1) were studied for their creatinine clearance (CLcr; ml/min/1.73m2), Fractional excretion of Na (FENa; %), Tubular reabsorption of PO4 (TRP; %), urinary Ca over creatinine ratio (UCa/cr); as well as their levels (µg/L) and cumulated doses (g) of cyclosporin before and at 0.5, 1, 2, 3 (n=28), 6 (n=24), 12 (n=21), 36 (n=17) and 60 months (n=8) after liver transplantation (OLT). Diagnoses were : biliary atresia (n=16), tyrosinemia (n=2), Wilson's disease (n=2), a-1-antitrypsin deficiency (n=2), fulminant hepatitis (n=1), a-beta-lipoproteinemia (n=1), miscellaneous (n=4). After OLT, patients received triple immunosuppressive therapy during 1 yr (Cyclo/tacrolimus, steroids and azathioprin) and single thereafter. Results : The overall survival rate is 91%. Both glomerular and tubular functions are tabulated below : (Table) CLcr was correlated to cyclosporin levels (Spearman's test; n=124; p=0.03). At 12 mo, CLcr was correlated to cumulated doses of cyclosporin (n=13; p=0.055). The same correlations were not established for the patients on tacrolimus. Tubular functions when expressed as POrr was improved by OLT, but remained at the lower limit of normal owing to patients with underlying renal diseases. There was a tendency to hypercalciuria immediately post-OLT certainly due to high doses of steroids. In addition to the above observations, the exact role of the numerous other nephrotoxic factors was unascertainable. In conclusion, the main alteration in kidney function was acute and seen in the early phases post-OLT. Both glomerular and tubular functions were satisfactory with medium follow-up suggesting that cyclosporin-induced renal sclerosis can be limited by cautious use.Table