A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of among 30,685 Japanese Individuals.

Background: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FE). Further studies on FE in hypouricemic individuals are needed for a more accurate diagnosis of RHUC.

Methods: In 30,685 Japanese health-examination participants, we genotyped the two most common nonfunctional variants of (NFV-), W258X (rs121907892) and R90H (rs121907896), in 1040 hypouricemic individuals (SUA ≤ 3.0 mg/dL) and 2240 individuals with FE data. The effects of NFV- on FE and SUA were also investigated using linear and multiple regression analyses.

Results: Frequency of hypouricemic individuals (SUA ≤ 3.0 mg/dL) was 0.97% (male) and 6.94% (female) among 30,685 participants. High frequencies of those having at least one allele of NFV- were observed in 1040 hypouricemic individuals. Furthermore, NFV- significantly increased FE and decreased SUA, enabling FE and SUA levels to be estimated. Conversely, FE and SUA data of hypouricemic individuals are revealed to be useful to predict the number of NFV-.

Conclusions: Our findings reveal that specific patterns of FE and SUA data assist with predicting the number of nonfunctional variants of causative genes for RHUC, and can also be useful for practical diagnosis of RHUC even before genetic tests.