ESPN 53rd Annual Meeting

ESPN 2021


 
Hyperuricemia is strongly dependent on renal function and hyperglycemia, which limits its clinical utility as a predictor of HNF1B nephropathy
MARCIN KOłBUC 1 BEATA BIENIAś 2 SANDRA HABBIG 3 MATEUSZ F. KOłEK 4 MARIA SZCZEPAńSKA 5 KATARZYNA KILIś-PSTRUSIńSKA 6 ANNA WASILEWSKA 7 PIOTR ADAMCZYK 8 RAFAł MOTYKA 1 MARCIN TKACZYK 9 PRZEMYSłAW SIKORA 2 BODO B. BECK 10 MARCIN ZANIEW 1

1- DEPARTMENT OF PEDIATRICS, UNIVERSITY OF ZIELONA GóRA, ZIELONA GóRA, POLAND
2- DEPARTMENT OF PEDIATRIC NEPHROLOGY, MEDICAL UNIVERSITY OF LUBLIN, LUBLIN, POLAND
3- DEPARTMENT OF PEDIATRICS, UNIVERSITY HOSPITAL OF COLOGNE, COLOGNE, GERMANY
4- DEPARTMENT OF ANIMAL PHYSIOLOGY, FACULTY OF BIOLOGY, UNIVERSITY OF WARSAW, WARSAW, POLAND
5- DEPARTMENT OF PEDIATRICS, FACULTY OF MEDICAL SCIENCES IN ZABRZE, MEDICAL UNIVERSITY OF SILESIA IN KATOWICE, ZABRZE, POLAND
6- DEPARTMENT OF PAEDIATRIC NEPHROLOGY, WROCLAW MEDICAL UNIVERSITY, WROCLAW, POLAND
7- DEPARTMENT OF PEDIATRIC NEPHROLOGY, UNIVERSITY HOSPITAL, BIALYSTOK, POLAND
8- DEPARTMENT OF PEDIATRICS, FACULTY OF MEDICAL SCIENCES IN KATOWICE, MEDICAL UNIVERSITY OF SILESIA IN KATOWICE, KATOWICE, POLAND
9- DEPARTMENT OF PEDIATRICS, IMMUNOLOGY AND NEPHROLOGY, POLISH MOTHERS MEMORIAL HOSPITAL RESEARCH INSTITUTE, LODZ, POLAND
10- INSTITUTE OF HUMAN GENETICS AND CENTER FOR MOLECULAR MEDICINE COLOGNE, UNIVERSITY OF COLOGNE, FACULTY OF MEDICINE AND UNIVERSITY HOSPITAL COLOGNE, COLOGNE, GERMANY
 
Introduction:

Mutations in the hepatocyte nuclear factor-1beta (HNF1B) gene are considered to be one of the most common genetic causes of congenital anomalies of the kidneys and urinary tract (CAKUT). Diagnosis of HNF1B-related disease is difficult, and individuals with mutations in HNF1B are likely undiagnosed. One of the features, which could serve as a predictor of the disease, is hyperuricemia. However, neither a causal relationship nor its predictive value have been proven. We thus assessed this in children with CAKUT, both with (mut+) and without HNF1B mutations (mut-).

Material and methods:

We performed a retrospective analysis of clinical characteristics of pediatric patients tested for HNF1B mutations, collected in a national registry. The most recent, age- and sex-dependent pediatric norms for sUA were used.

Results:

108 children were included in the study, comprising 43 mut+ patients and 65 mut- subjects. Mean serum uric acid (sUA) was higher in mut+ than in mut- subjects (p = 0.006), and hyperuricemia was more prevalent in HNF1B carriers (42.5% vs. 15.4%, p = 0.002). The groups were similar with respect to kidney function and fractional excretion of uric acid (FEUA). Hyperglycemia and pancreatic anomalies were more prevalent in the mut+ group. After exclusion of patients with these confounders, which are independent predictors of sUA, the difference in hyperuricemia was accounted for. Kidney function and FEUA were also independent predictors of sUA. Mutation was identified as a minor determinant of sUA. The potential of hyperuricemia to predict mutation was low, and addition of hyperuricemia to a multivariate logistic regression model did not increase its accuracy.

Conclusions:

Hyperuricemia is relatively common in children with CAKUT due to HNF1B mutations, however its direct association with this molecular defect remains unproven. Its dependence on kidney function and hyperglycemia diminishes its ability to predict HNF1B disease.