Hypouricaemia and acute kidney injury: a hereditary condition should be considered.

Abstract

I read with interest the case report by Tadokoro et al.1 about a 17-year-old woman, presumably of Japanese ethnicity, who presented with acute kidney injury (AKI) following a basketball game. In view of the clinical course and computed tomography images, a diagnosis of exercise-induced acute kidney injury (EIAKI) was made; notably, uric acid (UA) was 1.3 mg/dl on admission. Although the association of EIAKI with hypouricaemia (by convention defined as a serum urate concentration of <2 mg/dl)2 was duly acknowledged, I was surprised that the authors did not elaborate on the potential causes of this finding. A UA level of 1.3 mg/dl in the context of AKI is highly unusual and should alert the clinician to the possibility of an underlying defect in renal UA reabsorption. Specifically, renal hypouricaemia (RHUC), a genetically heterogenous disorder caused by mutations in two major renal tubular UA transporters (URAT1, encoded by SLC22A12, and GLUT9, encoded by SLC2A9), predisposes affected individuals to kidney stones and recurrent AKI, the latter typically provoked by exercise.3 Although certainly qualifying as an orphan disease, the prevalence of RHUC varies significantly and is reasonably common in certain Asian regions, particularly in Japan, where the estimated prevalence reaches 0.5% in the general population.4 The pathophysiology of EIAKI is incompletely understood. UA is a powerful antioxidant and hypouricaemia may trigger an oxidative imbalance during exercise; resultant renovascular spasm shares similarities with ischaemia-reperfusion injury.2,3