McDonald B R, Kirmani S, Vasquez M, Mehta R L
Department of Medicine, University of California Medical Center, San Diego 92103.
Am J Med. 1991 Mar;90(3):386-91.
Carboplatin, a new analogue of cisplatin used in the treatment of ovarian carcinoma, has been demonstrated to be less nephrotoxic than its predecessor. To date, hundreds of cycles of therapy have been given without a significant incidence of renal failure. We report herein two cases of acute, nonoliguric renal failure in patients receiving intraperitoneal (IP) carboplatin as chemotherapy for advanced ovarian carcinoma. Each patient had received extensive previous treatment with cisplatin. The baseline serum creatinine levels in the patients were 0.9 and 1.1 mg/dL, respectively. After four cycles of IP carboplatin in Patient 1 and five cycles of IP carboplatin in Patient 2, the serum creatinine levels abruptly rose to 9.0 and 9.5 mg/dL, respectively, within a week after administration of therapy. No other primary etiologies for acute renal failure could be identified in either patient. One patient required hemodialysis briefly. Renal biopsy specimens were obtained from both patients. Patient 1 had focal and moderate interstitial nephritis with mild periglomerular fibrosis. Patient 2 had an edematous interstitium with a diffuse mononuclear cell infiltrate, focal interstitial hemorrhage, and toxic changes in proximal and distal tubules on electron microscopy. Treatment with oral prednisone at 1 mg/kg/day with a rapid taper over 4 weeks was done in both cases with the serum creatinine levels eventually dropping to 4.6 and 2.0 mg/dL, respectively. Acute interstitial nephritis and renal failure to this extent have not been previously reported with carboplatin therapy. The literature regarding carboplatin is reviewed with respect to the pathophysiology of its nephrotoxicity.
卡铂是一种用于治疗卵巢癌的新型顺铂类似物,已被证明其肾毒性低于其前身。迄今为止,已进行了数百个疗程的治疗,未出现明显的肾衰竭发生率。我们在此报告两例接受腹腔内(IP)卡铂化疗晚期卵巢癌患者发生急性非少尿性肾衰竭的病例。每位患者此前都接受过广泛的顺铂治疗。患者的基线血清肌酐水平分别为0.9和1.1mg/dL。在患者1接受四个疗程的IP卡铂治疗和患者2接受五个疗程的IP卡铂治疗后,血清肌酐水平在治疗给药后一周内分别突然升至9.0和9.5mg/dL。在这两名患者中均未发现其他急性肾衰竭的主要病因。一名患者短暂需要血液透析。两名患者均获取了肾活检标本。患者1有局灶性中度间质性肾炎伴轻度肾小球周围纤维化。患者2间质水肿,有弥漫性单核细胞浸润、局灶性间质出血,电子显微镜下近端和远端小管有中毒性改变。两例患者均采用口服泼尼松1mg/kg/天并在4周内快速减量治疗,血清肌酐水平最终分别降至4.6和2.0mg/dL。此前尚未有卡铂治疗导致如此严重的急性间质性肾炎和肾衰竭的报道。本文就卡铂肾毒性的病理生理学对相关文献进行了综述。