The role of renal chloride channel mutations in kidney stone disease and nephrocalcinosis.
Recent advances in molecular biology have characterised a new class of chloride channels (CLCs) that are referred to as voltage-gated CLCs. To date nine such voltage-gated CLCs (CLC-1 to CLC-7, CLC-Ka and CLC-Kb, which are encoded by the genes CLCN1 to CLCN7, CLC-Ka and CLC-Kb, respectively) have been identified in mammals. Mutations in two of these, CLC-5 and CLC-Kb, have been defined in the hypercalciuric nephrolithiasis disorders of Dent's disease and a form of Bartter's syndrome, respectively. In addition, other forms of Bartter's syndrome have been defined with mutations involving the bumetanide-sensitive sodium-potassium-chloride cotransporter (NKCC2) and the potassium channel ROMK. Finally, mutations of the thiazide-sensitive sodium-chloride cotransporter (NCCT) are associated with Gitelman's syndrome, in which hypocalciuria and hypomagnesaemia are notable features. These molecular genetic studies have increased our understanding of the renal tubular mechanisms that regulate mineral homeostasis.
Thakker
R V
RV
Medical Research Council Molecular Endocrinology Group, Medical Research Council Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK. rthakker@rpms.ac.uk
D000818:Animals; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007669:Kidney Calculi / Q000235:genetics*; D009397:Nephrocalcinosis / Q000235:genetics*
D018118:Chloride Channels