CLCN5 and Hypercalciuria: On the basis of these findings, an alternative hypothesis can be advanced: the genes involved in the development of the DD phenotype in the CLCN5− patients cause CKD through mechanisms other than those in the CLCN5+ patients, where the associations between hypercalciuria and nephrocalcinosis and between nephrocalcinosis and CKD seem to indicate the direct involvement of the ClC-5 alteration in the pathogenesis of nephrocalcinosis and subsequent CKD, as shown in animal models (Cebotaru et al. 2005).