Alport syndrome

Disease Description (Causes and Symptoms)

• Definition summary: A group of hereditary kidney diseases caused by structural abnormalities in the basement membranes—especially the glomerular basement membrane, the cochlear basement membrane of the inner ear, and the basement membranes around the retina and lens—due to abnormalities in the type IV collagen (alpha-3,4,5) genes. The X-linked form (COL4A5) is the most common; autosomal recessive and dominant forms (COL4A3/COL4A4) are rare.
• Pathophysiology: Abnormal type IV collagen synthesis → structural abnormalities of the glomerular basement membrane, such as thinning, thickening, and lam splitting (basket-weave appearance) → glomerular filtration impairment and progressive fibrosis, leading to chronic kidney failure. Abnormalities in the basement membranes of the inner ear and eyes cause sensorineural hearing loss, anterior lenticonus, and peripheral retinal changes.
• Main symptoms
  • Hematuria: Begins in childhood as microscopic or gross hematuria (the most common initial finding).
  • Proteinuria and features of nephrotic syndrome (progressing with age).
  • Progressive decline in kidney function → progression to end-stage renal disease (ESRD) (particularly rapid in males with the X-linked form).
  • Sensorineural hearing loss: Usually begins in childhood to adolescence and gradually worsens.
  • Eye findings: Anterior lenticonus (conical deformation of the front surface of the lens), perimacular flecks, and others (less common than hearing loss).

Treatment

• Goal: Preserve kidney function and manage complications (however, definitive genetic treatment has not yet been established as standard treatment).
• Medication treatment
  • RAAS inhibitors (ACE inhibitors or ARBs): The key treatment because they reduce proteinuria and help preserve kidney function. Consider starting early when proteinuria or hypertension is present.
  • Blood pressure control: The recommended target varies depending on the patient’s situation, so consult the treating physician.
  • Treatment of symptoms and complications: Treatment for CKD-related conditions such as hyperkalemia and anemia.
• Procedures/Surgery
  • At the chronic kidney failure stage, dialysis or kidney transplantation (immunosuppression is required after transplantation).
  • Acute decline in kidney function related to anti-glomerular basement membrane (anti-GBM) antibodies may rarely occur after transplantation, so monitoring is necessary.
• Supportive care and lifestyle management
  • A low-salt diet and appropriate control of protein intake (depending on kidney function).
  • Avoid dehydration and nephrotoxic medications (e.g., some antibiotics and NSAIDs).
  • Regular hearing tests (audiograms) and ophthalmologic examinations (lens and retinal examinations).
  • Review of family history and genetic counseling (family screening is recommended).
• Other
  • Participation in clinical research, such as gene therapy or new drug studies, may be considered (consult the treating physician).
• Precautions (points of caution, risk of complications, and self-management)
  • Avoid nephrotoxic medications such as NSAIDs, as they can accelerate worsening of kidney function.
  • Kidney function and medication adjustments, particularly for RAAS inhibitors, may be necessary before infection treatment or surgery.
  • If planning a pregnancy, counseling based on kidney status and genetic findings is necessary (female carriers may also develop declining kidney function).
  • Monitor progression through regular tests, including urine tests, blood pressure measurements, blood tests, hearing tests, and ophthalmologic examinations.

Outpatient Visit Checklist (Including Items to Bring and Example Questions)

• Items to bring
  • List of current medications and supplements (including doses and administration times)
  • Previous test results (blood tests, urine tests, urine protein-to-creatinine ratio, and urine microscopy findings)
  • Previous kidney biopsy report, if available, and genetic test results, if available
  • Family history information (family members’ history of hematuria, hearing loss, chronic kidney failure, transplantation, and other relevant conditions)
  • Recent hearing and ophthalmologic examination results, if possible
  • Symptom diary (timing, frequency, and color changes of hematuria; timing of worsening hearing; changes in vision; etc.)
• Items to check before the outpatient visit
  • Recent blood pressure readings (records measured at home)
  • Presence or absence of changes in urine color or edema
  • Whether you are taking diuretics, antihypertensive medications, or anticoagulants
• Example questions to prepare for asking during the outpatient visit (can be used directly during the consultation)
  • “Based on my current urine test and blood pressure results, should I start a RAAS inhibitor (ACEi/ARB)?”
  • “Is genetic testing recommended, and what do the results mean for my family?”
  • “If my kidney function begins to decline, how often should I undergo testing?”

Examples of General Questions to Ask the Doctor

• What are the main side effects of this medication (e.g., an ACE inhibitor/ARB), and how should I respond if side effects occur?
• For my condition, what lifestyle changes are most important for slowing the worsening of kidney function?
• When do you think a kidney transplant will become clinically necessary, and what special precautions are needed after transplantation?
• Do you recommend screening family members (genetic testing/urine testing)? If so, who should be tested first?

Examples of Disease-Specific Questions

• Once my (or my family member’s) genetic test results are available, what tests should be recommended for my children and siblings, and when should they be performed?
• My current proteinuria is mild. When is the optimal time to start a RAAS inhibitor? (Ask about the criteria for starting treatment and target proteinuria/blood pressure levels, etc.)