Novel Approach to Enhance the Sensitivity of Hereditary Renal Hypouricemia Detection via the Relationship Between Serum Uric Acid and Its Fractional Excretion

Le résumé fourni par la source

Background: Hereditary Renal Hypouricemia (HRH) is characterized by low Serum Uric Acid (SUA) levels and high Fractional Excretion of Uric Acid (FEUA) due to defective urate tubular reabsorption. Generally asymptomatic, it can cause exercise-induced acute kidney injury; and although global incidence is low, Japanese studies (population with higher prevalence) have identified milder phenotypes, suggesting potential underdiagnosis. We hypothesised that the ratio between SUA and FEUA (SUFE Ratio) could improve the diagnostic sensitivity of HRH, and analysed it together with SUA, FEUA and SUA2 (a proxy for SUFE Ratio) in a pediatric cohort from our centre (Study Cohort) and published cases (Validation Cohort), as well as genotype-phenotype correlations. Methods: The Study Cohort included 9 HRH patients and 58 Controls with normal renal function, while the Validation Cohort consisted of 45 Cases from the Literature. We assessed SUA-FEUA correlation and compared Cases and Controls using Kruskal-Wallis and Fisher’s tests with Bonferroni-adjusted p-values. ROC curves were generated to evaluate diagnostic thresholds with AUCs and various cutoffs for each parameter, and permutation pAUC tests were used to compare predictor performances at high sensitivity values. Results: SUA and FEUA showed a strong negative correlation across both Cohorts. All predictors differed significantly between Cases and Controls (p < 0.001). SUA, SUA2 and SUFE Ratio performed comparably, achieving 100% sensitivity with ≥90% specificity while FEUA showed a tendency toward slightly lower diagnostic performance. Increasing SUA diagnostic threshold to ~3 mg/dL dramatically improved sensitivity, consistent with Kawamura et al. (2021). Genotype-phenotype correlation mirrored that from this last study for SLC22A12 mutations but not for heterozygous SLC2A9 variants, suggesting possibly unrecognized genetic factors in our Cohorts. Conclusion: Our study proposes and validates new diagnostic markers for HRH and supports adjusting SUA thresholds to improve sensitivity, especially in underdiagnosed populations. These findings may help reduce false negatives and prevent patients complications. Further research is needed to refine diagnostic strategies, particularly in non-Japanese populations.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.