Screening for CLCN5 mutation in renal calcium stone formers patients

Maria Alice P Rebelo,Nordeval C Araújo,William B Guggino,Bruno F Botelho,Sabrina V Martini,Vera Tostes,Marcelo M Morales

doi:10.1590/s0001-37652005000100007

Abstract

Thirty-five patients (23 males and 12 females), age 35 +/- 13 years old, presenting either idiopathic calcium nephrolithiasis, nephrocalcinosis or mild renal failure with idiopathic calcium nephrolithiasis were selected for the analysis of low molecular weight proteinuria and the possible mutations occurrence in the chloride channel gene CLCN5. The urinary ratio of beta2-microglobulin and creatinine (beta2M/Cr) was very high in a transplanted woman with nephrocalcinosis (> 3.23 mg/mmol) and slightly high in five patients (> 0.052 or < 1.0 mg/mmol) with multiple urological manipulations. Other studied patients showed beta2M/Cr ratio at normal range (0.003-0.052 mg/mmol) without gender difference (p > 0.05). Mutation analysis of CLCN5 gene was performed in 26 patients of 35 selected (11 with idiopathic hypercalciuria; 6 men with normal calciuria; 3 with mild renal insufficiency and 6 with nephrocalcinosis) and was normal in all subjects even in those with abnormal molecular weight proteinuria. CLCN5 gene mutation is not a common cause of kidney stone disease or nephrocalcinosis in a group of Brazilian patients studied.

Highlights

The genetic background of the idiopathic calcium nephrolithiasis is unknown
Scheinman et al in a study that screened 101 patients for low molecular weight proteinuria (LMWP) and presenting idiopathic hypercalciuric found only slight abnormalities in the LMWP in nine patients, none of them had a mutation in CLCN5 (Scheinman et al 2000)
Among all factors involved in the lithogenesis, the present study aims to search for a CLCN5 gene mutation in the context of renal idiopathic calcium lithiasis and/or nephrocalcinosis patients

Summary

Introduction

The genetic background of the idiopathic calcium nephrolithiasis is unknown. Some advances have been made in the understanding of disorders that can exhibit nephrolithiasis as a symptom such as primary hyperoxaluria (Danpure et al 1993), cystinuria (Stoller et al 1999) and Dent’s disease (Xlinked hypercalciuria and nephrolithiasis) The genetic background of the idiopathic calcium nephrolithiasis is unknown. Hypercalciuric man, apparently idiopathic, that was a true case of asymptomatic Dent’s disease (Scheinman et al 1993), has excited a stone investigators group to look for CLCN5 (gene that encodes for ClC-5 chloride channel) gene mutations. Mutation in CLCN5 is the pathophysiological basis for Dent’s disease that can present calcium stone formation with idiopathic hypercalciuria, nephrocalcinosis and renal insufficiency. Scheinman et al in a study that screened 101 patients for low molecular weight proteinuria (LMWP) and presenting idiopathic hypercalciuric found only slight abnormalities in the LMWP in nine patients, none of them had a mutation in CLCN5 (Scheinman et al 2000). The same procedure can be used for the screening of genetic defect carrier female (Scheinman et al 2000)

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Conclusion