Acute renal failure after alpha interferon therapy for chronic hepatitis C in renal transplant patients

Sixteen renal transplant (RT) patients (10 men, 6 women, aged 49 +/- 10 years) with chronic hepatitis C received alpha interferon(IFN alpha) therapy (intron A(R), Schering Plough) al a dose of 3 x 10(6) units SC 3 times a week, scheduled for 24 consecutive weeks. At the beginning of the study all had a stable renal function since at least 12 months (mean serum creatinine -SCr- 121 +/- 38 mmol/l). Fourteen patients were receiving cyclosporin A (CsA) either alone (1)or in combination with steroids and/or azathioprine -AZA- (double therapy: 8, triple therapy: 5), two patients were on conventional therapy The mean daily doses of CsA were 2.6 mg/kd i.e. a mean whole blood trough level of 104 ng/ml. Six patients experienced renal failure either acute (5) or subacute (1) within 7 to 24 weeks after the start of IFN alpha therapy. Their mean SCr increased from 105 +/- 31 mmol/l to 207 +/- 63 mmol/l (p = 0.02) with de-novo proteinuria in one case (1 g/d) and an increase in pre-existing proteinuria in 2; 3 remained without proteinuria. The histological study showed in all cases a diffuse interstitial edema associated with dilatation of peritubular capillaries; mild inflammatory infiltrates were present in only 3 cases; mild glomerular lesions were not always found (glomerular ischemia, mesangial hypertrophy). There was no vascular lesions IFN alpha was withdrawn in these 6 patients, associated with methylprednisolone pulses in 5 cases. Renal function improved in two cases, stabilized in one and progressed to end stage renal failure in 3 within 4 to 12 months. Four patients had iterative renal biopsies showing in ail cases diffuse interstitial fibrosis. This subgroup of patients did not statistically differ al the start of the study from those who did not develop renal failure according to baseline immunosuppression, HLA matching, total peripheral blood lymphocyte (PBL) count, PBL subtypes. IFN alpha therapy was associated with acute or subacute renal failure in 37% of patients. The most prominent histological finding was a diffuse interstitial edema of rapid onset, without signs of cellular or vascular rejection. Thus we do not recommend to use IFN alpha therapy in RT patients with chronic hepatitis C, until the mechanisms of the subsequent renal failure be more understood.