Cyclosporine (CsA), a widely used immunosuppressive
drug, is an effective treatment of sight-threatening posterior idiopathic
uveitis. CsA's main side effect is nephrotoxicity. The aim of this single-center prospective cohort study (conducted in a tertiary care teaching hospital in Paris, France) was to assess the long-term renal tolerance of a low-dose CsA treatment in patients with previously healthy kidneys on clinical,
biologic, and pathologic criteria. Forty-one patients treated with 4.3 +/- 1.6 mg/kg body wt per day CsA for 44.9 +/- 3.6 mo were included. Mean follow-up was 55.4 +/- 0.2 mo. BP, CsA trough level, and renal function were prospectively monitored together with blood
urea,
creatinine clearance, GFR, and effective renal plasma flow. Eleven patients underwent serial kidney biopsies before and after 2 yr of a 4 +/- 0.9 mg/kg daily CsA treatment. Sustained low-dose CsA treatment induced a significant increase in plasma
creatinine (P < 0.0001), a significant decrease in
creatinine clearance (P < 0.0001), and isotopic GFR (P < 0.0001) over time. The highest dose induced more severe alterations in any of the renal parameters than the lowest dose. Prevalence of
hypertension was particularly high. Histopathologic data showed significant interstitial
fibrosis (P < 0.003) and tubular
atrophy (P < 0.003) after 2 yr. Low-dose long-term CsA treatment induces significant renal impairment and a high incidence of
hypertension. Our study suggests that lowering daily dosage may prevent CsA-induced nephrotoxicity if a daily dose of < or =3 mg/kg is used. Whether once established it is reversible is still prospective, although the occurrence of interstitial
fibrosis in the kidney would argue against reversibility.