Literature abstracts
Literature abstracts
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DOI：
10.1007/s004670100022
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发表时间：
2001-06
影响因子：
3
通讯作者：
G. Markowitz;G. Appel;P. Fine;A. Fenves;N. Loon;S. Jagannath;J. Kuhn;Adam D. Dratch;V. D’Agati
中科院分区：
文献类型：
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作者：
G. Markowitz;G. Appel;P. Fine;A. Fenves;N. Loon;S. Jagannath;J. Kuhn;Adam D. Dratch;V. D’Agati
塌陷性局灶节段性肾小球硬化症（FSGS）是一种独特的临床病理实体，最常见于出现肾功能不全和肾病综合征的年轻非裔美国患者。此前唯一与塌陷性FSGS相关的流行病学因素是艾滋病病毒感染。本文报道了一个特殊的7例患者群体的临床病理发现，这些患者年龄较大，为白种人，艾滋病病毒阴性，且在积极治疗恶性肿瘤期间（6例为多发性骨髓瘤，1例为转移性乳腺癌）发生了塌陷性FSGS。尽管肿瘤治疗方案包括4例患者使用长春新碱，5例患者使用阿霉素，2例患者使用顺铂，1例患者接受全身放疗，但所有患者共同使用的唯一药物是帕米膦酸（阿可达）。所有患者在使用帕米膦酸之前肾功能正常。患者开始使用帕米膦酸治疗时，剂量为每月静脉注射90mg或低于此剂量，其中2例患者每月剂量增加到180mg，3例患者增加到360mg。患者在出现肾功能不全（平均血清肌酐为3.6mg/dl）和完全肾病综合征（平均24小时尿蛋白排泄量为12.4g/d）之前，接受帕米膦酸治疗15至48个月。帕米膦酸是双膦酸盐类的一员，广泛用于治疗恶性肿瘤高钙血症和溶骨性转移。按照每月静脉注射90mg的推荐剂量，肾毒性很少见；然而，在动物模型中，更高剂量已产生肾毒性。帕米膦酸治疗与肾功能不全发生之间的时间关联、超过推荐水平的递增剂量使用以及肾小球和肾小管损伤的独特模式，强烈提示一种药物相关的足细胞和肾小管毒性机制。这些数据首次表明塌陷性FSGS与治疗药物毒性相关。
Collapsing focal segmental glomerulosclerosis (FSGS) is a distinct clinicopathologic entity seen most commonly in young African American patients who present with renal insufficiency and nephrotic syndrome. The only epidemiologic factor previously linked to collapsing FSGS is HIV infection. Here clinicopathologic findings are reported for a distinctive population of seven patients, who were older, Caucasian, and HIV negative and developed collapsing FSGS during active treatment of malignancy (multiple myeloma in six patients and metastatic breast carcinoma in one). Although oncologic treatment regimens included vincristine for four patients, doxorubicin for five patients, cisplatin for two patients, and total-body irradiation for one patient, the only agent common to all patients was pamidronate (Aredia). All patients had normal renal function before the administration of pamidronate. Patients began therapy with pamidronate at or below the recommended dose of 90 mg, intravenously, monthly, which was increased to 180 mg monthly in two patients and 360 mg monthly in three patients. Patients received pamidronate for 15 to 48 mo before presentation with renal insufficiency (mean serum creatinine, 3.6 mg/dl) and full nephrotic syndrome (mean 24-h urinary protein excretion, 12.4 g/d). Pamidronate, which is a member of the class of bisphosphonates, is widely used in the treatment of hypercalcemia of malignancy and osteolytic metastases. At the recommended dose of 90 mg, intravenously, monthly, renal toxicity is infrequent; however, higher doses have produced nephrotoxicity in animal models. The temporal association between pamidronate therapy and the development of renal insufficiency, the use of escalating doses that exceed recommended levels, and the distinctive pattern of glomerular and tubular injury strongly suggest a mechanism of drug-associated podocyte and tubular toxicity. These data provide the first association of collapsing FSGS with toxicity to a therapeutic agent.