OVERVIEW

What is hereditary nephritis?

Hereditary nephritis (Alport syndrome) is a genetic disorder caused by gene mutations, primarily characterized by hematuria, proteinuria, and progressive renal dysfunction. Some patients may also exhibit extrarenal manifestations such as sensorineural hearing loss, ocular abnormalities, or esophageal leiomyomas.

This disease is generally incurable, but renal function can be preserved by controlling proteinuria, reducing damage to renal tubular epithelial cells, and slowing the progression to kidney failure. However, without timely intervention, it may lead to renal failure, severely impacting quality of life.

Is hereditary nephritis common?

To date, there is no population-based epidemiological data on hereditary nephritis.

Who is most likely to develop hereditary nephritis?

Individuals with mutations in the genes encoding type IV collagen in the glomerular basement membrane. Specifically:

• 85% of hereditary nephritis cases are caused by COL4A5 gene mutations (which encodes the α5 chain of type IV collagen in the glomerular basement membrane), leading to X-linked dominant Alport syndrome (XL Alport syndrome).
• 15% result from COL4A3 or COL4A4 gene mutations, causing autosomal Alport syndrome, predominantly the autosomal recessive form (AR Alport syndrome).

SYMPTOMS

What are the common manifestations of hereditary nephritis?

Patients with hereditary nephritis often have a family history and may exhibit the following clinical manifestations:

• Hematuria: The most common clinical manifestation, seen in nearly 100% of patients as microscopic hematuria (defined as fewer than 3 red blood cells per high-power field under a microscope, usually undetectable to the naked eye). About 60% of patients experience episodic gross hematuria (typically more than 1 mL of blood per liter of urine, visible as red-colored urine).
• Proteinuria: Absent or minimal in early stages but progressively worsens with age, potentially leading to heavy proteinuria.
• End-stage renal disease: Severe kidney function deterioration as the disease progresses.
• Sensorineural hearing loss: Initially subtle but progressively worsens with age, potentially impairing daily communication.
• Ocular abnormalities: Usually does not affect vision but progresses with declining kidney function. May also manifest as worsening myopia.

How does hereditary nephritis progress?

The condition gradually worsens with age. In XL Alport syndrome, male patients experience more severe progression, with 90% developing kidney failure before age 40. In AR Alport syndrome, nearly all patients develop kidney failure before age 30.

CAUSES

What causes hereditary nephritis?

Hereditary nephritis is a genetic disorder caused by gene mutations.

Is hereditary nephritis inherited? How is it inherited?

Yes, it is inherited, primarily through X-linked dominant inheritance.

DIAGNOSIS

How to diagnose hereditary nephritis?

When diagnosing hereditary nephritis, doctors primarily consider family history, persistent glomerular hematuria, or hematuria accompanied by proteinuria. Further confirmation is achieved through medical history inquiries and relevant auxiliary examinations.

What tests are needed for hereditary nephritis?

Patients are generally required to undergo the following tests:

• Urinalysis: Midstream urine samples are collected and repeatedly examined to determine if there is persistent hematuria or hematuria accompanied by proteinuria.
• Kidney function tests: Assess the progression of kidney damage.
• Search for extrarenal manifestations: Pure-tone audiometry, slit-lamp examination, or fundoscopy to determine if the eyes or ears are affected. These are non-invasive tests, but eye examinations require pupil-dilating drops.

If any of the above criteria are met, a skin biopsy is required. If abnormalities are found, a diagnosis can be made. If normal, further kidney biopsy and/or genetic testing is performed.

What diseases can hereditary nephritis be easily confused with?

Hereditary nephritis may be confused with diseases causing persistent familial hematuria (e.g., thin basement membrane nephropathy, familial IgA nephropathy) or diseases leading to kidney failure combined with deafness (e.g., MYH9-related disorders, Bartter syndrome).

Doctors differentiate these conditions by reviewing family history, conducting urinalysis, kidney biopsies, and genetic testing.

TREATMENT

Which department should I visit for hereditary nephritis?

Nephrology.

What are the treatment options for hereditary nephritis?

Treatment goals: Control proteinuria, prevent renal tubular epithelial cell damage, inhibit renal interstitial fibrosis, slow the progression to renal failure, and preserve kidney function.

• Medication:
  • Indications for treatment: Patients with Alport syndrome and a urine protein/creatinine ratio > 0.2 mg/mg or urine protein excretion > 4mg/(m²·h) require treatment; male patients with microalbuminuria and a high risk of ESRD before age 30 (e.g., large deletions, nonsense mutations, or frameshift mutations in the COL4A5 gene) should initiate angiotensin blockade therapy.
  • ACE inhibitors (ACEIs, e.g., ramipril, enalapril) are the first-line treatment, with dosing adjusted by the physician based on age and condition. Alternatively, angiotensin receptor blockers (ARBs) and aldosterone receptor antagonists may be used in combination.
• Hearing impairment and ocular involvement: Symptomatic and supportive treatment should be provided by relevant specialists.
• Renal replacement therapy: Patients progressing to ESRD (eGFR < 15 ml/(min·1.73m²)) require renal replacement therapy, including dialysis or kidney transplantation.

What are the common adverse effects of medications for hereditary nephritis?

• ACEIs may cause orthostatic hypotension, dry cough, angioedema, and hyperkalemia.
• ARBs have fewer side effects but may increase the risk of acute kidney injury when combined with ACEIs.
• ACEIs and ARBs should be used cautiously in women of childbearing age who plan to conceive.

Is surgery required for hereditary nephritis?

Kidney transplantation may be considered for patients with ESRD, with favorable outcomes: 20-year patient survival is 70.2%, and graft survival is 46.8%. However, about 3% of male transplant recipients may develop anti-glomerular basement membrane disease.

Can hereditary nephritis be completely cured?

No, but disease progression can be controlled with medication or surgery.

Can hereditary nephritis lead to death?

Yes, if it progresses to ESRD, timely and standardized treatment is essential to prevent fatal outcomes.

DIET & LIFESTYLE

How to Follow Up During Hereditary Nephritis?

Once diagnosed with hereditary nephritis, patients should undergo close monitoring, receive appropriate genetic counseling, and follow dietary guidance.

• Urine-related tests, including urinalysis, urine protein-to-creatinine ratio, and 24-hour urine protein quantification, are recommended every 3 months.
• Renal function assessments, including blood biochemistry and 24-hour creatinine clearance rate, are recommended every 6 months.

What Dietary Precautions Should Hereditary Nephritis Patients Take?

Protein intake requirements vary depending on the disease stage. Patients should follow their doctor's and dietitian's guidance to control protein intake and opt for high-quality protein sources.

Does Hereditary Nephritis Affect Fertility?

For patients or family members with fertility plans, genetic testing is recommended before pregnancy to identify specific mutation sites. A clinician with expertise in clinical genetics should provide proper genetic counseling and fertility guidance based on the genetic profile.

PREVENTION

How to prevent hereditary nephritis?

Early diagnosis, eugenics, and preventing the birth of children with the disease.