Author(s): Platz KP, Mueller AR, Blumhardt G, Bachmann S, Bechstein WO,
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Abstract Nephrotoxicity represents a serious side effect of immunosuppression following liver transplantation. In order to compare the nephrotoxic action of CsA and FK506 in a clinical setting, we evaluated the incidence of early and late nephrotoxicity in 121 patients, 60 of whom were randomly assigned to CsA- and 61 to FK506-based immunosuppression. Early postoperative renal insufficiency (between PODs 0 and 30; SCr 1.5-3 mg/dl) was observed to a similar extent in patients treated with CsA (38.3\%) and FK506 (42.6\%). Early postoperative acute renal failure (ARF) (SCr > 3 mg/dl) was observed in 18.0\% of patients in the FK506 treatment group and 18.3\% of patients receiving CsA therapy. Approximately half the patients with ARF required hemodialysis (CsA: 11.7\%; and FK506: 8.2\%). All patients with early postoperative ARF requiring hemodialysis survived for more than one year. New onset of late ARF (between PODs 30 and 365) was observed in 6.6\% of patients receiving FK506 therapy and in 1.7\% in the CsA treatment group as a result of severe infection with multiple organ failure syndrome (MOFS). There was 100\% mortality in patients with late ARF requiring hemodialysis. Etiology and prognosis of early and late ARF seem to be completely different. Early ARF was associated with severe coagulopathy and a rise in bilirubin and free hemoglobin, and was accompanied by impaired liver function. Mean onset of hemodialysis in CsA-treated patients was POD 1 and in FK506-treated patients POD 6, which disclosed a different time course of drug-specific nephrotoxicity of CsA and FK506 in early ARF. In contrast, late ARF occurred in both treatment groups only as a part of the MOFS in association with severe infections, an observation consistent with the assumption of overimmunosuppression rather than a primary nephrotoxic effect. Late renal insufficiency appeared in 23.3\% of CsA- and in 29.4\% of FK506-treated patients, and represented a slowly progressing form of drug-specific nephrotoxicity of CsA and FK506. These preliminary results demonstrate a similar outcome in terms of both early and late nephrotoxicity, but longer follow-up will delineate the overall efficacy and toxicity in humans.
This article was published in Transplantation
and referenced in Journal of Clinical & Cellular Immunology