Chapter 12 - Dent's Disease

Abstract

Dent’s disease is an inherited disorder whose clinical features result from renal tubular epithelial dysfunction. Dent’s disease is associated with mutations in CLCN5 in about 60% of cases, and with mutations in OCRL1 in another 15%. The major features of Dent’s disease reflect disturbances in proximal tubular solute reabsorption. The most consistent of these is low-molecular-weight (LMW) proteinuria, which is essentially a universal feature in all affected males and, in less extreme degrees, in many carrier females. LMW proteinuria is dramatically milder in females, but it is sufficiently consistent as to have value as a screening tool, though some carriers have normal excretion of LMW proteins. The urinary proteome in Dent’s disease reflects failure to reabsorb filtered proteins. It does not include proteinsthat are secreted into the urine in response to tubular injury.Although kidney stones occur in only half of patients, nephrolithiasis is one of the distinctive features of Dent’s disease. Hypercalciuria is nearly universal before the onset of renal failure, and the stones are composed of calcium, either oxalate or phosphate. Hypercalciuria is moderate in adolescents and young adults with Dent’s disease, in the range of 4-6 mg/kg body weight, but in children under age 10 years it can be much greater and can exceed 10 mg/kg. Nephrocalcinosis may reflect a disturbance beyond hypercalciuria, as the degree of hypercalciuria in Dent’s disease is no more severe than in a typical patient with idiopathic hypercalciuria. Rickets only occurs in a minority of patients with Dent’s disease but it is often severe and disabling in those patients.