Alport Syndrome

Alport Syndrome – Treatment Overview

Introduction
Alport syndrome is a genetic disorder of type IV collagen affecting the basement membranes of the kidneys, inner ear, and eyes. It is most commonly inherited in an X-linked pattern (COL4A5 mutation), but autosomal recessive (COL4A3, COL4A4) and autosomal dominant forms exist. The hallmark features are:

• Kidney disease: Hematuria, progressive proteinuria, leading to chronic kidney disease (CKD) and end-stage renal disease (ESRD).

• Hearing loss: Sensorineural deafness, usually developing in adolescence or early adulthood.

• Eye abnormalities: Lenticonus, corneal dystrophy, and retinal changes.

Treatment is primarily supportive, aiming to slow kidney disease progression, manage complications, and address hearing/visual impairment.

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Treatment Options and Doses

1. Renoprotective Therapy (Mainstay)

• ACE Inhibitors (first-line): Delay progression of kidney disease by lowering intraglomerular pressure and reducing proteinuria.

  • Enalapril: Start with 0.1–0.5 mg/kg/day orally in children, titrate to effect (max 20 mg/day).

  • Adults: 5–20 mg orally once or twice daily.

• ARBs (alternative or adjunct if ACEI not tolerated):

  • Losartan: 25–100 mg orally once daily.

• Early initiation (even with microalbuminuria) is recommended.

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2. Management of Advanced CKD/ESRD

• Dialysis: Hemodialysis or peritoneal dialysis for end-stage disease.

• Kidney Transplantation: Definitive therapy.

  • Outcomes are excellent, though rare cases of anti-GBM nephritis may occur post-transplant.

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3. Hearing Loss Management

• Regular audiometric screening from childhood.

• Hearing aids for sensorineural hearing loss.

• Cochlear implants in selected severe cases.

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4. Ophthalmologic Care

• Regular eye examinations.

• Corrective lenses for visual impairment.

• Surgery may be required for anterior lenticonus or cataracts.

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5. Experimental and Emerging Therapies

• SGLT2 inhibitors (dapagliflozin, empagliflozin): Being studied for additional renoprotective effect.

• Bardoxolone methyl: Investigated as a kidney-protective agent.

• Gene therapy and exon-skipping approaches: Under development to correct underlying mutations.

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6. Supportive Measures

• Salt restriction and blood pressure control.

• Avoidance of nephrotoxic agents (NSAIDs, aminoglycosides).

• Genetic counseling for affected families.