title: Two male siblings with hereditary renal hypouricemia and exercise-induced ARF.
abstract: 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 micromol/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 micromol/L), and fractional excretion of uric acid (FE(UA)) 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 micromol/L]) and high urinary urate excretion (FE(UA), 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).
authors.affiliation: Department of Nephrology, Akebono Clinic, Kumamoto, Japan. tanaka@matusita-kai.or.jp
authors.forename: Motoko
authors.initials: M
authors.lastname: Tanaka
authors.forename: Kazuko
authors.initials: K
authors.lastname: Itoh
authors.forename: Kazunori
authors.initials: K
authors.lastname: Matsushita
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Matsushita
authors.forename: Naoki
authors.initials: N
authors.lastname: Wakita
authors.forename: Masataka
authors.initials: M
authors.lastname: Adachi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonoguchi
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kitamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Hosoyamada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Endou
authors.forename: Kimio
authors.initials: K
authors.lastname: Tomita
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000235:genetics; D000328:Adult; D001416:Back Pain / Q000209:etiology; D002352:Carrier Proteins / Q000235:genetics; D018389:Codon, Nonsense; D003404:Creatinine / Q000097:blood; D015444:Exercise; D005091:Exons / Q000235:genetics; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000150:complications* / Q000235:genetics; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000172:deficiency* / Q000235:genetics; D027701:Organic Cation Transport Proteins; D010375:Pedigree; D011339:Probenecid; D011718:Pyrazinamide; D012420:Running; D014527:Uric Acid / Q000097:blood* / Q000652:urine; D014545:Urinary Calculi / Q000209:etiology
chemical_list: D002352:Carrier Proteins; D018389:Codon, Nonsense; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; C103862:urate transporter; D014527:Uric Acid; D011718:Pyrazinamide; D003404:Creatinine; D011339:Probenecid