Abstract: SA-PO0645
Novel Approach to Enhance the Sensitivity of Hereditary Renal Hypouricemia Detection via the Relationship Between Serum Uric Acid and Its Fractional Excretion
Session Information
- Monogenic Kidney Diseases: Tubular and Other
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Fortes-González, Pedro, Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, GA, Spain
- Urisarri, Adela, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
- Carrera Cachaza, Noa C., Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, GA, Spain
- Sánchez Cazorla, Eloísa, Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, GA, Spain
- Garcia-Gonzalez, Miguel A., Instituto de Investigacion Sanitaria de Santiago de Compostela, Santiago de Compostela, GA, Spain
Group or Team Name
- NefroCHUS.
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.