The exact mechanism of acute kidney injury remains elusive, but it is believed that uric acid serves as an antioxidant, and in states of hypouricaemia this protective role is lost. Kaneko et al. demonstrated in a 15 year old girl with idiopathic renal hypouricaemia an oxidative imbalance soon after exercise with a predisposition to exercise-induced acute renal failure. In contrast, some patients may present with more minor renal features including nephrolithiasis or hematuria. In 2002, Enomoto et al. established that URAT1 transporter was responsible for tubular reabsorption of urate. SLC22A12 encodes the protein URAT1 and loss of function mutations are responsible for majority of patients with idiopathic renal hypouricaemia. The W258X variant of URAT1 is a typical mutation found in Japanese and Korean populations. R428 allele frequency of W258X in the general population in Japan was found to be as high as 1.9%. Heterozygous carriers of URAT1 mutations are usually asymptomatic but they may develop nephrolithiasis. Prevalence of hypouricaemia in Japan varies between 0.15% and 0.23% from the analysis of serum urate levels in 1730 school children. In Korea, the prevalence of hypouricaemia in healthy adults is 3.3%. Therefore, school-age children who plan to performing competitive sporting activities are advised to have their serum uric acid level checked. Loss of function mutations affecting URAT1 have not been previously reported in a Caucasian population. However, single case reports from European patients presenting with clinical and biochemical features of hereditary renal hypouricaemia exist. Tzovaras et al. tested nine Greek subjects with primary renal hypouricaemia. All had serum uric acid levels,2.5 mg/dl, associated with a FEurate.10% and no other known cause of hypouricaemia. No definite pathogenic mutations were detected in this series and just one silent polymorphism in exon 2 of the SLC22A12 gene was noted. It is questionable why hereditary renal hypouricaemia is apparently so rare in Caucasian populations. Either the prevalence of URAT1 mutations is indeed low in this population, or a decreased awareness of this disease and its presentation outside of the Far East allows cases to go undetected. Even in Japan, there are patients who have clinical features of renal hypouricaemia but no SLC22A12 mutations. Very recently, a genome-wide association study was performed in 6890 African Americans and 21708 European participants in order to try and identify risk alleles for elevated serum urate, associated with gout. A novel URAT1 variant was identified and was associated with a reduction in serum urate of around 1.2 mg/dl per copy of the minor allele. Urate transport studies demonstrated a reduction in the urate transport for the G65W URAT1 variant. This study validates heterozygous changes within URAT1 as a determinate of reduced serum urate levels. In this study the variant allele provided a protective affect against gout, but one may postulate that this may also be an at-risk allele for the hypouricaemia. Both biochemically and clinically, a single heterozygous change in URAT1 may be significant. Cheong et al. reported a W258X homozygous mutation in a 7 year old child.