Predictive, Preventive and Personalized Medicine & Molecular Diagnostics

Biography

Biography: Shinichiro KOGA

Abstract

BACKGROUND: Hypouricemia has reported to a risk factor to develop cardiovascular event in men and women 1). In adults with renal hypouricemia (RHUC), excercise-induced acute kidney injury (EIAKI) is major commorbidity, but its prediction and prevention is not yet satisfied. Japanese RHUC frequently has mutation in exons 1 and 4 in urate transporter 1 (URAT1). In Japanese type 1 RHUC, W258X in exon 4 is the most frequent mutation that extincts urate transportation 2)3). CLINICAL PRESETATION: A healthy 33-year-old male consulted to primary care physician with chief complaint of epigastric dullness and anorexia 3 days after 1.2 miles anaerobic road race. He was immediately transferred to our institute because serum creatinin 3.6 mg/dL and blood urea nitrogen 33.7 mg/dL implied him acute kidney injury. As past medical history, he has received no further evaluation for hypertension from preschool age and serum hypouricemia in annual health check. No abnormality was shown in urine dipstick so far. No relevant medical history on his family. Abdominal US show no difference, atrophy, hydronephrosis, nor lithiasis. Contrast CAT imaging was not performed in acute phase. Hypouricemia was detected on admission, so EIAKI on RHUC was raised as clinical diagnosis. After admission, hydration 1,500-2,500mL/day was continued for 5 days and symptoms had dissappeared soon, but serum uric acid had linearly decreased from 2.4 mg/dL (FEUA 57.1%; day 1) to 1.0 mg/dL (54.8 %; day 10). Serum creatinine decreased gradually from 3.69 to 1.52 mg/dL so he discharged in day 10 of hospitalization after preventive education. MOLECULAR DIAGNOSIS: Peripheral blood on day 9 was subjected to URAT1/SLC22A12 exons 1 and 4 DNA sequence, as described elsewhere 4). No mutation was detected in exon 1. W258X homologous mutation was detected in exon 4 on URAT1 DNA; This is the causative gene mutation of RHUC type 1. Extracellular release and degradation pathways of this blunted protein has not reported. History and clinical course of patient was agree with genetic diagnosis described above. DISCUSSION: Having URAT1 DNA mutation, excercise, particularly anaerobic, generally need to have enough prerequisite water to prevent dehydration. Anaerobic exercise should avoid in having cold, or having antipyretics. Frequency of EIAKI recurrence is not well known in experienced patients with EIAKI. It has not yet shown whether antioxydatives (vitamin C, E) is effective for EIAKI prevention. REFERENCES: 1) Odden MC, et al. Am J Kidney Dis 2014;64:550-7. 2) Enomoto A, et al.Nature 2002;417:447-52. 3) Kamatani Y, et al. Nat Genet 2010;42:210-5. 4) Matsuo H, et al. Am J Hum Genet 2008;83:744-51.