Diseases In Depth - Dent Disease
What is Dent disease?
Dent disease is a rare X-linked kidney disorder characterized by hypercalciuria and low molecular weight proteinuria, and is often accompanied by nephrolithiasis and nephrocalcinosis that can lead to renal failure. Other common manifestations are hypophosphatemia and osteomalacia.
How is Dent disease diagnosed?
Laboratory Findings
- Proteinuria usually in the range of 1-2 gm/day, half of which is low molecular weight (LMWP) (<30,000 Da). Low molecular weight proteins that can be clinically measured include alpha 1 microglobulin and retinol binding protein. ß2 microglobulin is another low molecular weight protein that is often measured, but it is not stale in acidic urine and therefore not recommended for this purpose.
- Hypercalciuria in the range of 4-6 mg/kg body weight if kidney function is preserved
- Low levels of parathyroid hormone
- Increased levels of 1,25 vitamin D
- Hypophosphatemia and relative hyperphosphaturia with normal serum calcium levels
- Aminoaciduria, glycosuria, hypokalemia
Radiologic findings
Patients can have presence of kidney stones or nephrocalcinosis. When analyzed stones are made of calcium oxalate or calcium phosphate.
Genetic screening/testing
Testing for the genes that cause Dent disease 1 (CLCN5) or Dent disease 2 (ORCL1) can be obtained through commercial laboratories, although many insurance companies will not pay for this testing.
Treatment of Dent disease
Hypercalciuria is thought to be the major factor that causes kidney stones and nephrocalcinosis in patients with Dent disease. Therefore it is reasonable to attempt to reduce urinary calcium by restricting dietary sodium intake and prescribing a thiazide diuretic. Caution has to be applied in young patients who might develop volume depletion and hypokalemia. Recently, animal studies in a model of Dent Disease have suggested that a high citrate diet may delay the loss of kidney function. Therefore some clinicians recommend a high citrate diet or prescribe potassium citrate. No studies are yet available to support the efficacy of either approach in humans with Dent disease.
