In a study of 25 patients with Dent's disease, 9 of 15 men, and one of 10 women suffered end-stage kidney disease by the age of 47.
Genetics
Dent disease 1
Dent's disease is a X-linked recessive disorder. The males are prone to manifesting symptoms in early adulthood with symptoms of calculi, rickets or even with kidney failure in more severe cases. In humans, gene CLCN5 is located on chromosome Xp11.22, and has a 2238-bp coding sequence that consists of 11 exons that span 25 to 30 kb of genomic DNA and encode a 746-amino-acid protein. CLCN5belongs to the family of voltage-gated chloride channel genes that have about 12 transmembrane domains. These chloride channels have an important role in the control of membrane excitability, transepithelial transport, and possibly cell volume. The mechanisms by which CLC-5 dysfunction results in hypercalciuria and the other features of Dent's disease remain to be elucidated. The identification of additional CLCN5 mutations may help in these studies.
Dent disease 2
Dent disease 2 is associated with the OCRL gene. Both Lowe syndrome and Dent disease can be caused by truncating or missense mutations in OCRL.
As of today, no agreed-upon treatment of Dent's disease is known and no therapy has been formally accepted. Most treatment measures are supportive in nature:
Thiazide diuretics have been used with success in reducing the calcium output in urine, but they are also known to cause hypokalemia.
* In rats with diabetes insipidus, thiazide diuretics inhibit the NaCl cotransporter in the renal distal convoluted tubule, leading indirectly to less water and solutes being delivered to the distal tubule. The impairment of Na transport in the distal convoluted tubule induces natriuresis and water loss, while increasing the reabsorption of calcium in this segment in a manner unrelated to sodium transport.
Amiloride also increases distal tubular calcium reabsorption and has been used as a therapy for idiopathic hypercalciuria.
* A combination of 25 mg of chlorthalidone plus 5 mg of amiloride daily led to a substantial reduction in urine calcium in Dent's patients, but urine pH was "significantly higher in patients with Dent’s disease than in those with idiopathic hypercalciuria, and supersaturation for uric acid was consequently lower."
For patients with osteomalacia, vitamin D or derivatives have been employed, apparently with success.
Some lab tests on mice with CLC-5-related tubular damage showed a high-citrate diet preserved kidney function and delayed progress of kidney disease.
History
Dent's disease was first described by Charles Enrique Dent and M. Friedman in 1964, when they reported two unrelated British boys with rickets associated with renal tubular damage characterized by hypercalciuria, hyperphosphaturia, proteinuria, and aminoaciduria. This set of symptoms was not given a name until 30 years later, when the nephrologist Oliver Wrong more fully described the disease. Wrong had studied with Dent and chose to name the disease after his mentor. Dent's disease is a genetic disorder caused by mutations in the gene CLCN5, which encodes a kidney-specific voltage-gated chloride channel, a 746-amino-acid protein with 12 to 13 transmembrane domains. It manifests itself through low-molecular-weight proteinuria, hypercalciuria, aminoaciduria and hypophosphataemia. Because of its rather rare occurrence, Dent's disease is often diagnosed as idiopathic hypercalciuria, i.e., excess calcium in urine with undetermined causes.
