Dent disease

Dent disease is a rare X-linked renal tubular disorder primarily affecting the proximal tubules of the kidneys. It is characterized by low-molecular-weight (LMW) proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis (kidney stones), and progressive renal failure. The disease predominantly affects males, while female carriers are usually asymptomatic or mildly affected. Dent disease exists in two forms: Dent disease 1 (caused by mutations in the CLCN5 gene encoding a chloride/proton exchanger in the proximal tubule) and Dent disease 2 (caused by mutations in the OCRL gene, which also causes Lowe syndrome). Both forms share similar renal manifestations. The hallmark feature is LMW proteinuria, which is present in virtually all affected males. Hypercalciuria occurs in the majority of patients and predisposes to nephrocalcinosis and kidney stone formation. Other proximal tubular dysfunction may include aminoaciduria, phosphaturia (which can lead to rickets or osteomalacia), glycosuria, and uricosuria, reflecting a partial or complete Fanconi syndrome. Progressive chronic kidney disease is common, with many affected males developing end-stage renal disease between the third and fifth decades of life. There is currently no disease-specific cure for Dent disease. Management is supportive and aimed at slowing disease progression and managing complications. Thiazide diuretics may be used to reduce hypercalciuria, though their use must be carefully monitored due to potential side effects including hypokalemia and volume depletion. Citrate supplementation may help prevent kidney stone formation. ACE inhibitors or angiotensin receptor blockers may be considered to reduce proteinuria. A high fluid intake is generally recommended. Dietary modifications, vitamin D supplementation, and phosphate replacement may be necessary in patients with rickets. Renal replacement therapy, including dialysis or kidney transplantation, may ultimately be required for patients who progress to end-stage renal disease.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Dent disease