NDT Advance Access published online on November 24, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl634
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Renal outcome after ciclosporin-induced nephrotoxicity
1Department of Nephrology, Pitié Salpétrière Hospital, 2Department of Biostatistics and Medical Information, Pitié Salpétrière Medical University, 3Department of Ophtalmology, and 4Department of Biochemistry, Pitié Salpétrière Hospital, Paris, France
Correspondence and offprint requests to: Correspondence and offprint request to: Dr Isabelle Tostivint, Service de Néphrologie, Hôpital Pitié Salpétrière, 83 Boulevard de l’Hôpital, 75013 Paris, France. Email: isabelle.tostivint{at}psl.aphp.fr
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Abstract |
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Background. Renal outcome after ciclosporin (CsA) is not clear in most studies involving patients with many renal comorbid conditions. We first report on renal function recovery after CsA in previously healthy kidney patients.
Methods. Uveitis patients, enroled in a unique single centre cohort follow-up study initiated in 1987, were prospectively evaluated for plasma creatinine and glomerular filtration rate (GFR) before, during (>2 years) and after (>6 months) CsA therapy. We hypothesized that CsA alters renal function progressively over time according to two additive exponential components (irreversible and reversible) and used a mixed linear model with exponential speed parameters maximizing the likelihood.
Results. Twenty-seven patients treated for 60±34 months (CsA 5.1±2.5 mg/kg/day) were followed up for 56±42 months after CsA withdrawal. Baseline creatinine was 0.92±0.15 mg/dl. The reversible effect of CsA was quantified as a 0.11±0.07 mg/dl increase in creatinine/100 mg CsA/day (P<0.001) and a 6.0±3.7 ml/min/1.73 m2 decrease in GFR/100 mg CsA/day (P<0.0001). The irreversible effect was quantified as a 0.03±0.05 mg/dl increase in creatinine/100 g cumulative CsA received (P<0.007) and a decrease of 3.3±3.9 ml/min/1.73 m2 GFR/100 g CsA.
Conclusions. Although significant decrease in GFR is induced by low-dose CsA therapy in previously healthy kidney patients, renal function recovery is possible after CsA withdrawal and best predicted by CsA daily dosage. Irreversible loss in GFR is correlated to cumulated CsA exposure. The lowest CsA dosage and shortest exposure time effect as well as unlimited renal monitoring are required in order to provide the best long-term renal outcome.
Keywords: ciclosporin; glomerular filtration rate; hypertension; nephrotoxicity; reversibility; uveitis