Genetic and clinical phenotype of Dent disease in Chinese children and the etiological analysis of early - onset chronic kidney disease

TL;DR

This study examines the genetic and clinical features of Dent disease in Chinese children, finding that some may develop chronic kidney disease early in life.

Contribution

The study expands the genetic spectrum of Dent disease and identifies early clinical indicators of chronic kidney disease progression in pediatric patients.

Findings

16 previously unreported mutations in CLCN5 and OCRL genes were identified in Dent disease patients.

Seven patients progressed to chronic kidney disease during childhood, with six having Dent disease type 1.

Nephrolithiasis, nephrocalcinosis, and acute kidney injury were significantly more common in patients who developed CKD.

Abstract

A prominent feature of Dent disease (DD) is the progressive decline in renal function, with 30% - 80% of male patients advancing to end-stage renal disease between the ages of 30 and 50 years. However, limited research exists on the chronic kidney disease (CKD) progression in pediatric patients with DD. This study aimed to retrospectively analyze the clinical features, genetic variant spectrum, and prognosis of pediatric patients with DD and explore the factors associated with early renal failure during childhood in these patients.

We analyzed the genetic backgrounds, clinical phenotypes, and laboratory data of 23 unrelated patients with DD.

All patients were males with low-molecular-weight proteinuria. CLCN5 variants were detected in 19 patients (Dent disease type 1, DD1), and OCRL variants were identified in 4 patients (Dent disease type 2, DD2). Sixteen mutations have not been reported previously. During follow-up, progression to CKD was documented in 7 patients: 6 with DD1 and 1 with DD2. CKD stages were distributed as follows: 4 patients at stage II, 2 at stage III, and 1 at stage V. Nephrolithiasis (100% vs 30.76%, P = 0.011), nephrocalcinosis (85.33% vs 15.38%, P = 0.010), and acute kideny injury (100% vs 0%, P < 0.001) were significantly more common in those CKD patients with DD1.

This study expands the genetic spectrum of Dent disease and highlights that some pediatric patients may progress to CKD during childhood. CKD progression may be associated with early occurrences of nephrolithiasis, nephrocalcinosis, and acute kidney injury.

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