Two male siblings with hereditary renal hypouricemia and exercise-induced ARF
Two male siblings with hereditary renal hypouricemia and exercise-induced ARF
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DOI：
10.1053/j.ajkd.2003.08.032
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发表时间：
2003-12-01
影响因子：
13.2
通讯作者：
Tomita, K
中科院分区：
文献类型：
--
作者：
Tanaka, M;Itoh, K;Tomita, K
家族性肾性低尿酸血症合并运动性急性肾功能衰竭（ARF）是罕见的。45岁男性，剧烈运动后腹痛、呕吐、少尿。基于高血清肌酐（SCr）水平（5.1 mg/dL [451 mumol/L]）诊断为ARF。保守治疗2周内肾功能完全恢复（肌酐清除率[Ccr]， 100.4 mL/min [1.67 mL/s]）。缓解后，实验室结果显示血清尿酸（SUA）为0.8 mg/dL (48 mumol/L)，尿酸（FEUA）分数排泄为46%。最终诊断为ARF合并特发性肾性低尿酸血症。排除其他可能增加尿酸排泄的疾病。由于在吡啶酰胺和苯溴马龙负荷试验中均仅观察到轻微反应，因此认为他是分泌前重吸收障碍型。弟弟（42岁）在剧烈运动后也有腰痛和中背痛发作，自29岁以来至少有5次类似发作。每次攻击中SCr水平都升高。低尿酸血症（SUA, 1.0 mg/dL [59 μ mol/L]）和高尿尿酸排泄（FEUA, 65.7%）也被检测到。在没有任何特殊治疗的情况下，肾功能几乎完全恢复。2例患者放射学检查显示双侧尿石症可能由高尿尿酸排泄引起。对两兄弟中已知调节血尿酸水平的尿酸阴离子交换器（URAT1基因）的序列分析显示，外显子4 （W258Stop）发生纯合突变，导致URAT1蛋白过早截断。父母和子女均出现URAT1基因杂合突变。本文首次报道了2例家族性肾性低尿酸血症并发运动性ARF的男性兄弟姐妹，并明确证实了相关基因（URAT1）的遗传异常。(C) 2003年由国家肾脏基金会。
Familial renal hypouricemia with exercise-induced acute renal failure (ARF) is rare. A 45-year-old man presented with abdominal pain, vomiting, and oliguria after severe exercise. The diagnosis was ARF based on high serum creatinine (SCr) level (5.1 mg/dL [451 mumol/L]). Renal function recovered completely within 2 weeks of conservative treatment (creatinine clearance [Ccr], 100.4 mL/min [1.67 mL/s]). After remission, laboratory results showed serum urate (SUA) of 0.8 mg/dL (48 mumol/L), and fractional excretion of uric acid (FEUA) of 46%. The final diagnosis was ARF associated with idiopathic renal hypouricemia. Other diseases that could increase the excretion of urate were excluded. Because only mild responses were observed both in pyradinamide and benzbromarone loading tests, he was considered to be a presecretory reabsorption disorder type. The younger brother (42 years old) also had episodes of low and middle back pain after severe exercise and experienced similar attacks at least 5 times since the age of 29. SCr level was elevated in every attack. Hypouricemia (SUA, 1.0 mg/dL [59 mumol/L]) and high urinary urate excretion (FEUA, 65.7%) also were detected. Renal function recovered almost completely without any specific treatment. Radiologic examination of the 2 cases showed bilateral urolithiasis probably caused by the high urinary urate excretion. Sequence analysis of a urate anion exchanger known to regulate blood urate level (URAT1 gene) in both brothers showed homozygous mutation in exon 4 (W258Stop), resulting in a premature truncated URAT1 protein. Both their parents and their children showed heterozygous mutation of the URAT1 gene. This is the first report of the 2 male siblings of familial renal hypouricemia complicated with exercise-induced ARF, with definite demonstration of genetic abnormality in the responsible gene (URAT1). (C) 2003 by the National Kidney Foundation.