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Internal Medicine

Dent’s disease

Renal tubular disorder characterized by manifestations of proximal tubule dysfunction, including low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive renal failure.

Renal tubular disorder characterized by manifestations of proximal tubule dysfunction, including low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive renal failure.

  • X-linked recessive inheritance
  • Caused by mutations in either the CLCN5 (Dent disease 1) or OCRL1 (Dent disease 2) genes that are located on chromosome Xp11.22 and Xq25

Pathophysiology

Characterized by PT dysfunction and LMW proteinuria, associated with hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive renal failure.

  • Associated with: Aminoaciduria, phosphaturia, glycosuria, uricosuria, kaliuresis, and impaired urinary acidification
  • Hypercalciuria and nephrocalcinosis

Clinical features

  • Bone pain and difficulty in walking (due to rickets)
  • Abdominal pain and haematuria (symptoms of renal stones)

Extra-renal manifestations:

  • Mild intellectual impairment
  • Hypotonia
  • Cataract

Complications

  • Rickets
  • Osteomalacia
  • End-stage renal failure (30-80%)

Diagnosis

Diagnostic criteria:

All criterias have to be met
  1. LMW proteinuria (elevation of urinary excretion of Ī²2-microglobulin, Clara cell protein and/or RBP by at least 5-fold above the upper limit of normality)
  2. Hypercalciuria (> 4 mg/kg in a 24 h-hour collection or > 0.25 mg Ca2+ per mg creatinine on a spot sample)
  3. At least one of the following:
    • Nephrocalcinosis
    • Kidney stones
    • Hematuria
    • Hypophosphatemia
    • Renal insufficiency

Molecular genetic testing

Confirmatory test

Differential diagnosis:

Other causes of generalized dysfunction of the proximal tubules
  • Renal Fanconi syndrome
  • Oculocerebrorenal syndrome of Lowe (OCRL)

Management

The primary goals of treatment are to decrease hypercalciuria, prevent kidney stones and nephrocalcinosis, and delay the progression of CKD.

Interventions aimed at decreasing hypercalciuria and preventing kidney stones and nephrocalcinosis have not been tested in randomized controlled trials. Although thiazide diuretics can decrease urinary calcium excretion in boys with Dent disease, side effects limit their use. The effectiveness of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in preventing or delaying further loss of kidney function in children with proteinuria is unclear.

  • Thiazide diuretics (treat hypercalciuria)
  • High citrate diet (long-term control of hypercalciuria, delays progression of renal disease even in the apparent absence of stone formation)
  • Renal replacement therapy (cases of ESRD)
  • Vitamin D supplementation and phosphorus repletion (treatment of bone disease)
  • Human growth hormone (for growth failure)

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