Renal outcome after ciclosporin-induced nephrotoxicity.
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 m(2) 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 m(2) 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.
Tostivint
Isabelle
I
Service de Néphrologie, Hôpital Pitié Salpétrière, 83 Boulevard de l'Hôpital, 75013 Paris, France. isabelle.tostivint@psl.aphp.fr
du Montcel
Sophie Tezenas
ST
Jaudon
Marie Chantal
MC
Mallet
Alain
A
Le Hoang
Phuc
P
Bodaghi
Bahram
B
Deray
Gilbert
G
Bagnis
Corinne Isnard
CI
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003124:Colorimetry; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D014527:Uric Acid / Q000378:metabolism; D014605:Uveitis / Q000150:complications / Q000188:drug therapy*
D001786:Blood Glucose; D007166:Immunosuppressive Agents; D014527:Uric Acid; D016572:Cyclosporine; D003404:Creatinine