Two types of Dent disease

• Dent disease 1 (DD1): caused by mutations in the CLCN5 gene
• Dent disease 2 (DD2): caused by mutations in the OCRL gene, which can also cause a more severe condition called Lowe syndrome

Key symptoms and signs

• Protein in the urine (especially small proteins that are normally reabsorbed by the kidneys)
• High levels of calcium in the urine, which can lead to kidney stones or calcium deposits in the kidneys (nephrocalcinosis)
• Bone problems such as rickets (soft or weak bones), especially in children
• Progressive loss of kidney function, sometimes leading to kidney failure in adulthood
• Occasionally: short stature, mild learning difficulties, or cataracts (mostly in Dent disease type 2)

How is Dent disease diagnosed?

• Dent disease can be hard to recognize at first. It is often found when a urine test shows unexpected protein levels.
• The key sign is low-molecular-weight proteinuria, a specific type of protein loss.
• A genetic test can confirm the diagnosis and distinguish between Dent disease 1 and 2.
• Kidney biopsies are usually not needed if Dent disease is suspected based on lab tests and family history. 

The true number of people with Dent disease is expected to be higher than currently diagnosed, because the symptoms can vary and often go unnoticed for years.

Who should be tested?

• Males with unexplained protein in the urine, kidney stones, calcium in the kidneys, or early kidney problems
• Female relatives of affected individuals may be carriers and should be tested to understand the risk to future children.

Is there a treatment or cure?

There is no cure yet, but treatment can help manage symptoms and slow down kidney damage:

• Citrate supplements may reduce the risk of kidney stones
• Phosphate supplements (if low phosphate levels are found)
• Vitamin D and vitamin A monitoring and replacement, if needed
• Growth hormone in some cases for short stature
• Regular monitoring of kidney function and bone health is important
• Avoid routine use of:
  • Thiazide diuretics (risk of dehydration, especially in DD2)
  • ACE inhibitors/ARBs (limited benefit in Dent disease)

What about kidney transplants?

If kidney failure occurs, a transplant can be successful. However, special care is needed when considering a female carrier (like a mother or sister) as a kidney donor.

Follow-up and care

Patients should be seen regularly by kidney specialists (nephrologists), ideally in centers with experience in rare kidney diseases. Monitoring includes:

• Blood and urine tests
• Imaging (like kidney ultrasounds)
• Growth and bone health assessments