Dent’s disease: clinical features and molecular basis

Abstract

Dent's disease is an X-linked recessive renal tubulopathy characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive renal failure. LMWP is the most constant feature, while the other clinical manifestations show wide variability. Patients also present variable manifestations of proximal tubule dysfunctions, such as aminoaciduria, glucosuria, hyperphosphaturia, kaliuresis, and uricosuria, consistent with renal Fanconi syndrome. Dent's disease affects mainly male children, and female carriers are generally asymptomatic. In two-thirds of patients, the disease is caused by mutations in the CLCN5 gene, which encodes the electrogenic chloride/proton exchanger ClC-5. A few patients have mutations in OCRL1, the gene associated with the oculocerebrorenal syndrome of Lowe, which encodes a phosphatidylinositol-4,5-biphosphate-5-phosphatase (OCRL1). Both ClC-5 and OCRL1 are involved in the endocytic pathway for reabsorption of LMW proteins in the proximal tubule. This review will provide an overview of the important phenotypic characteristics of Dent's disease and summarize the molecular data that have significantly increased our comprehension of the mechanisms causing this disease.

The ratio of urinary α1-microglobulin to microalbumin can be used as a diagnostic criterion for tubuloproteinuria

“…However, mild to moderate proteinuria (less than 1 g/day, mainly low-molecularmost constant feature. It mainly affects male children, and female carriers are generally asymptomatic (11,12). The level of proteinuria often reaches the nephrotic range (13,14).…”

Diagnosis and treatment of Dent disease in 10 Chinese boys

“…A few patients have mutations in OCRL, which encodes a phosphatidylinositol-4, 5-biphosphate-5-phosphatase (OCRL). Both ClC-5 and OCRL1 are involved in the endocytic pathway for reabsorption of low molecular weight proteins in the proximal tubules (8,9).…”

Nephrology Quiz and Questionnaire

“…Mutations in ClC-5 allow greater amounts of PTH to be delivered to more distal parts of the proximal tubule, where PTH can then bind apically located PTH receptors and stimulate the internalization of the Npt2a protein, thus causing the development of phosphaturia (19). Receptor stimulation also increases the activity of the 1a-hydroxylase enzyme, thus causing increased production of 1,25(OH) 2 D. In turn, vitamin D increases gastrointestinal absorption of calcium, thus explaining the hypercalciuria present in these patients.…”