Rostaing L, Modesto A, Baron E, Cisterne J M, Chabannier M H, Durand D
Service de Néphrologie, CHU Rangueil, Toulouse, France.
Nephron. 1996;74(3):512-6. doi: 10.1159/000189444.
Sixteen kidney transplant (KT) patients (10 men, 6 women, aged 49 +/- 10 years) with chronic hepatitis C alpha-interferon (IFN-alpha) therapy (Intron A, Schering Plough) at a dose of 3 x 10(6) units subcutaneously 3 times a week. The treatment was scheduled for 24 consecutive weeks. Each patient had had stable renal function for at least 12 months prior to IFN-alpha therapy (mean serum creatinine, SCr, 121 +/- 38 mmol/l). Fourteen patients were receiving cyclosporin-A (CsA)-based immunosuppression and 2 patients were on conventional therapy. The patients' 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 IFN-alpha was withdrawn if SCr increased more than 25% from baseline, in which case a kidney biopsy was performed.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 subacute (n = 1) renal failure within 7-24 weeks after the onset of IFN-alpha therapy. Their mean SCr increased from 105 +/- 31 to 207 +/- 63 mmol/l (p = 0.02) with de novo proteinuria in 1 case (1 g/day) and an increase in preexisting proteinuria in 2. The other 3 patients did not develop proteinuria. In each case, histological study showed diffuse interstitial edema associated with dilation of the peritubular capillaries, whereas mild inflammatory infiltrates were present in only 3 cases and 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 IFN-alpha was withdrawn in these 6 patients, in association with methylprednisolone pulses in 5 cases.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. Four 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 those who did not, with respect to the following: baseline immunosuppression, HLA matching, total peripheral blood lymphocyte count or peripheral blood lymphocyte subtypes. IFN-alpha therapy was associated with acute or subacute renal failure in 37% of the patients. The most prominent histological finding was diffuse interstitial edema of rapid onset, without signs of cellular or vascular rejection. In conclusion, we do not recommend IFN-alpha therapy for KT patients with chronic hepatitis C, until the mechanisms of the subsequent renal failure are better understood.
16例肾移植（KT）患者（10例男性，6例女性，年龄49±10岁）接受慢性丙型肝炎α干扰素（IFN-α）治疗（Intron A，先灵葆雅公司），剂量为3×10⁶单位，皮下注射，每周3次。治疗计划持续24周。在接受IFN-α治疗前，每位患者的肾功能至少稳定12个月（平均血清肌酐，SCr，121±38 mmol/L）。14例患者接受基于环孢素A（CsA）的免疫抑制治疗，2例患者接受传统治疗。患者在接受IFN-α治疗期间，每2周检查一次SCr，若SCr较基线水平升高超过15%，则每周检查一次。若SCr较基线水平升高超过25%，则停用IFN-α，此时需进行肾活检。6例患者在IFN-α治疗开始后7 - 24周内发生急性（n = 5）或亚急性（n = 1）肾衰竭。他们的平均SCr从105±31升至207±63 mmol/L（p = 0.02），1例出现新发蛋白尿（1 g/天），2例原有蛋白尿增加。另外3例患者未出现蛋白尿。在每种情况下，组织学研究显示弥漫性间质水肿伴肾小管周围毛细血管扩张，而仅3例有轻度炎症浸润，并非总能发现轻度肾小球病变（肾小球缺血、系膜增生）。未发现血管病变。这6例患者停用IFN-α，其中5例联合甲泼尼龙冲击治疗。2例患者肾功能改善，1例稳定，3例在4 - 12个月内进展至终末期肾衰竭。其中4例患者进行了多次肾活检，每次均显示弥漫性间质纤维化。发生肾衰竭的患者在研究开始时与未发生肾衰竭的患者在以下方面无统计学差异：基线免疫抑制、HLA配型、外周血淋巴细胞总数或外周血淋巴细胞亚群。37%的患者IFN-α治疗与急性或亚急性肾衰竭相关。最突出的组织学表现是迅速出现的弥漫性间质水肿，无细胞或血管排斥迹象。总之，在更好地了解后续肾衰竭的机制之前，我们不建议对患有慢性丙型肝炎的肾移植患者进行IFN-α治疗。
