Renal hypouricemia: Prevention of exercise-induced acute renal failure and a review of the literature

Abstract

Isolated renal hypouricemia from defective uric acid reabsorption and/or secretion is a well-described entity, with a prevalence of 0.12% to 0.20% in Japan. It is rarely associated with exercise-induced acute renal failure (ARF). The etiology of ARF is debated. Prevention of ARF in renal hypouricemia has not been previously addressed. A 29-year-old Pakistani man had recurrent exercise-induced ARF. He was found to have isolated renal hypouricemia: serum uric acid 0.5 mg/dL, 24-hour urine uric acid 472 ± 25 mg (±SD), and fractional excretion of uric acid 55.2% to 69.4%. Both pyrazinamide and probenecid decreased fractional excretion of uric acid and uric acid excretion rate (UV Urate) in our patient, suggesting either a partial presecretory and postsecretory reabsorption defect or increased secretion. We investigated renal uric acid excretion during exercise in our patient and four control subjects. All five subjects underwent a physical fitness test (PFT). Our patient developed ARF. Uric acid excretion rate increased in our patient, from 0.48 mg/min at baseline to 1.49 mg/min 4 hours after the PFT, as did the urine uric acid to urine creatinine ratio ( U UA U Cr ) (0.29 to 1.49). In the controls, UV Urate and U UA U Cr were unchanged after the PFT: UV Urate was 0.46 ± 0.10 mg/min at baseline and 0.59 ± 0.04 mg/min 4 hours after the PFT, while U UA U Cr was 0.30 ± 0.04 at baseline and 0.36 ± 0.04 at 4 hours. All five subjects took allopurinol 300 mg daily for 5 days and repeated the PFT. In our patient, allopurinol prevented the ARF as well as the exercise-induced increases in UV Urate (0.28 mg/min to 0.22 mg/min) and U UA U Cr (0.25 to 0.17). In the controls, the UV Urate and U UA U Cr responses to exercise were not altered. We conclude that increased renal excretion of uric acid during exercise was responsible for the ARF in our patient with renal hypouricemia and that successful prophylaxis with allopurinol is possible. This is a US government work. There are no restrictions on its use.