Hyperuricemia Is an Early and Relatively Common Feature in Children with HNF1B Nephropathy but Its Utility as a Predictor of the Disease Is Limited.

Marcin Kołbuc,Beata Bieniaś,Sandra Habbig,Piotr Adamczyk,Mateusz F Kołek,Marcin Tkaczyk,Bodo B Beck,Katarzyna Kiliś-Pstrusińska,Maria Szczepańska,Przemysław Sikora,Marcin Zaniew,Anna Wasilewska,Rafał Motyka

doi:10.3390/jcm10153265

Abstract

Background: Hyperuricemia is recognized as an important feature of nephropathy, associated with a mutation in the hepatocyte nuclear factor-1B (HNF1B) gene, and could serve as a useful marker of the disease. However, neither a causal relationship nor its predictive value have been proven. The purpose of this study was to assess this in children with renal malformations, both with (mut+) and without HNF1B mutations (mut-). Methods: We performed a retrospective analysis of clinical characteristics of pediatric patients tested for HNF1B mutations, collected in a national registry. Results: 108 children were included in the study, comprising 43 mut+ patients and 65 mut- subjects. Mean sUA was higher and hyperuricemia more prevalent (42.5% vs. 15.4%) in HNF1B carriers. The two groups were similar with respect to respect to age, sex, anthropometric parameters, hypertension, and renal function. Renal function, fractional excretion of uric acid and parathyroid hormone level were independent predictors 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 an early and common feature of HNF1B nephropathy. A strong association of sUA with renal function and parathyroid hormone limits its utility as a reliable marker to predict HNF1B mutation among patients with kidney anomalies.

Highlights

Introduction distributed under the terms andHepatocyte nuclear factor 1β (HNF1B) is a critical transcription factor that regulates the development of the kidneys, pancreas, liver, and genital tract [1,2,3]
hepatocyte nuclear factor-1B (HNF1B) mutation carriers has not been adequately analyzed in other cohorts [4]. It remains unclear whether raised serum uric acid (sUA) is a feature of HNF1B-related disease and is directly related to mutation, or if this symptom is a byproduct of chronic kidney disease (CKD), which could be present during the course of the disease
We demonstrated that hyperuricemia is an early and prevalent feature in children with HNF1B nephropathy when compared to well-matched mutation negative patients

Summary

Introduction

Introduction distributed under the terms andHepatocyte nuclear factor 1β (HNF1B) is a critical transcription factor (encoded by the HNF1B gene) that regulates the development of the kidneys, pancreas, liver, and genital tract [1,2,3]. Hyperuricemia is a key hallmark of the disease that has been repeatedly reported in patients with HNF1B mutation [6,7,8,9,10,11,12,13,14,15]. The finding of elevated sUA levels in HNF1B mutation carriers has not been adequately analyzed in other cohorts [4]. Hyperuricemia is recognized as an important feature of nephropathy, associated with a mutation in the hepatocyte nuclear factor-1B (HNF1B) gene, and could serve as a useful marker of the disease. A strong association of sUA with renal function and parathyroid hormone limits its utility as a reliable marker to predict HNF1B mutation among patients with kidney anomalies

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