Early Urinary Biomarkers in Pediatric Autosomal Dominant Polycystic Kidney Disease (ADPKD): No Evidence in the Interest of Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL).

Marianthi Tsingos,Laura Merlini,Alexandra Goischke,Alexandra Wilhelm-Bals,Paloma Parvex,Marco Solcà

doi:10.3389/fped.2019.00088

Abstract

Background: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is increasingly diagnosed during childhood by the presence of renal cysts in patients with a positive familial history. No curative treatment is available and early detection and diagnosis confronts pediatricians with the lack of early markers to decide whether to introduce renal-protective agents and prevent the progression of renal failure. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a tubular protein that has been recently proposed as an early biomarker of renal impairment in the ADPKD adult population.Methods: Urinary NGAL (uNGAL) levels were measured in 15 ADPKD children and compared with 15 age and gender matched controls using parametric, non-parametric, and Bayesian statistics. We also tested the association of uNGAL levels with markers of disease progression, such as proteinuria, albuminuria, blood pressure, and Total Kidney Volume (TKV) using correlation analysis. TKV was calculated by ultrasound, using the ellipsoid method.Results: No difference in mean uNGAL levels was observed between groups (ADPKD: 26.36 ng/ml; Controls: 27.24 ng/ml; P = 0.96). Moreover, no correlation was found between uNGAL and proteinuria (P = 0.51), albuminuria (P = 0.69), TKV (P = 0.68), or mean arterial pressure (P = 0.90). By contrast, TKV was positively correlated with proteinuria (P = 0.04), albuminuria (P = 0.001), and mean arterial pressure (P = 0.03).Conclusion: uNGAL did not confirm its superiority as a marker of disease progression in a pediatric ADPKD population. In the contrary, TKV appears to be an easy measurable variable and may be promising as a surrogate marker to follow ADPKD progression in children.

Highlights

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent inherited monogenic kidney disease and affects 1/500 individual worldwide
Based on the data reported by Bolignano et al [17], we estimated that a sample size of 15 ADPKD patients and 15 controls would be sufficient to show urinary NGAL (uNGAL) differences between groups
Similar to a previous study conducted in the adult ADPKD population by Vareesangthip et al [29], we found no significant difference in uNGAL values between the two groups

Summary

Introduction

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent inherited monogenic kidney disease and affects 1/500 individual worldwide. It represents up to 5–10% of total end-stage renal disease [1, 2]. Mutations in PKD1 gene concern around 85% of the ADPKD population and are associated with a more severe renal impairment and disease progression. Given the fewer cyst burden and later age at diagnosis among PKD2-related ADPKD, PKD1-associated ADPKD is over-represented in pediatric patients [4]. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is increasingly diagnosed during childhood by the presence of renal cysts in patients with a positive familial history. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a tubular protein that has been recently proposed as an early biomarker of renal impairment in the ADPKD adult population

Methods

Results

Conclusion