ACUTE-RENAL-FAILURE IN KIDNEY-TRANSPLANT PATIENTS TREATED WITH INTERFERON-ALPHA-2B FOR CHRONIC HEPATITIS-C

Sixteen kidney transplant (KT) patients (10 men, 6 women, aged 49 +/- 10 years) with chronic hepatitis C alpha-interferon (IFN-alpha) therap y (Intron A(R), Schering Plough) at a dose of 3 x 10(6) units subcutan eously 3 times a week. The treatment was scheduled for 24 consecutive weeks. Each patient had had stable renal function for at least 12 mont hs prior to IFN-alpha therapy (mean serum creatinine, SCr, 121 +/- 38 mmol/l). Fourteen patients were receiving cyclosporin-A (CsA)-based im munosuppression and 2 patients were on conventional therapy. The patie nts' SCr was checked every 2 weeks while on IFN-alpha, or weekly if it increased more than 15% from baseline. IFN-alpha was withdrawn if SCr increased more than 25% from baseline, in which case a kidney biopsy was performed. Six patients experienced either acute (n = 5) or subacu te (n = 1) renal failure within 7-24 weeks after the onset of IFN-alph a therapy. Their mean SCr increased from 105 +/- 31 to 207 +/- 63 mmol /l (p = 0.02) with de novo proteinuria in I case(1 g/day) and an incre ase in preexisting proteinuria in 2. The other 3 patients did not deve lop proteinuria. In each case, histological study showed diffuse inter stitial edema associated with dilation of the peritubular capillaries, whereas mild inflammatory infiltrates were present in only 3 cases an d mild glomerular lesions were not always found (glomerular ischemia, mesangial hypertrophy). There were no vascular lesions. IFN-alpha was withdrawn in these 6 patients, in association with methylprednisolone pulses in 5 cases. Renal function improved in 2 cases, stabilized in 1 and progressed to end-stage renal failure in 3 within 4-12 months. Fo ur of these patients had iterative renal biopsies which showed diffuse interstitial fibrosis in each case. The patients who developed renal failure did not statistically differ at the start of the study from th ose who did not, with respect to the following: baseline immunosuppres sion, HLA matching, total peripheral blood lymphocyte count or periphe ral blood lymphocyte subtypes. IFN-alpha therapy was associated with a cute or subacute renal failure in 37% of the patients. The most promin ent histological finding was diffuse interstitial edema of rapid onset , without signs of cellular or vascular rejection. In conclusion, we d o not recommend IFN-alpha therapy for KT patients with chronic hepatit is C, until the mechanisms of the subsequent renal failure are better understood.