A comparison of renal function in cyclosporine- and FK-506-treated patients after primary orthotopic liver transplantation.

In this randomized controlled trial comparing FK-506 to CsA, we report parameters of nephrotoxicity in adult patients surviving > 90 days after orthotopic liver transplant (OLT). Patients randomized to FK-506 first received 0.15 mg/kg IV/day followed by 0.3 mg/kg PO/day. Doses were modified to avoid toxicity and to achieve FK-506 levels of 0.5 to 1.5 ng/ml. CsA was administered in the usual manner with dose adjustments to whole blood HPLC levels. A pre-OLT glomerular filtration rate (GFR) of > or = 30 ml/min/1.73/m2 and/or serum creatinine < or = 2.0 mg/dl were required for inclusion in the study. GFRs were obtained at post OLT days 28, 180, and 360. Other parameters of renal function evaluated were creatinine, magnesium, serum electrolytes, blood pressure, use of antihypertensives, and magnesium supplements. There were 38 patients in the FK-506 group and 34 in the CsA group. The mean days of follow up for each group was similar: 456 +/- 135 days for the FK-506 group and 451 +/- 112 days for the CsA group. The mean oral dose for the FK-506 group ranged from 0.13-0.16 mg/kg/day with mean FK-506 levels of 0.6-0.8 ng/ml. In the FK-506 group, there was a significant fall in the pre-transplant GFR from 89 +/- 31 ml/min/173 m2 to 43 +/- 15 ml/min/173 m2 at day 360. Similarly, for the CsA group, the pre-transplant GFR of 75 +/- 31 ml/min/1.73 m2 fell to 49 +/- 17 ml/min/1.73 m2 at day 360. At each time point studied, there was no significant difference in mean GFR between the two groups. There were no significant differences in the monthly mean values for creatinine, electrolytes, magnesium, or blood pressure between the two groups. Magnesium levels were in the low normal range (1.4-1.6 mEq/L), and the mean potassium levels in the high normal range (4.4-4.7 mEq/L). In both groups, a similar number of patients required magnesium supplementation or hypertensive medications. The nephrotoxicity of FK-506 given at low oral doses and with concomitant low levels was comparable to that of CsA. The two drugs were remarkably similar in their spectrum of electrolyte disturbances and incidence of hypertension.

RCT Entities:   Population Interventions Outcomes