What is Alport syndrome?

From the Guidelines

Alport syndrome patients should be treated with ACE inhibitors or angiotensin receptor blockers to slow kidney disease progression, and genetic counseling is essential for affected families. The condition is characterized by hematuria, proteinuria, progressive renal insufficiency, and sensorineural hearing loss, primarily affecting the kidneys, hearing, and eyes due to mutations in genes responsible for producing type IV collagen [ 1 ]. According to the most recent study on genetic evaluation of living kidney donor candidates [ 1 ], a comprehensive approach to genetic testing and interpretation is crucial for identifying potential donors and recipients with genetic diseases like Alport syndrome.

Key Considerations

• The primary goal of treatment is to slow kidney disease progression and manage associated symptoms [ 1 ].
• ACE inhibitors or angiotensin receptor blockers, such as enalapril 5-20 mg daily or losartan 25-100 mg daily, are recommended to reduce proteinuria and preserve kidney function [ 1 ].
• Blood pressure control is essential, with a target below 130/80 mmHg [ 1 ].
• Regular monitoring of kidney function, hearing tests, and eye examinations are necessary due to the multi-systemic nature of the disease [ 1 ].
• Genetic counseling is important for affected families, as Alport syndrome follows different inheritance patterns (X-linked, autosomal recessive, or autosomal dominant) [ 1 ].

Hearing Assessment

The American Academy of Pediatrics recommends hearing assessment in infants and children with risk indicators, including syndromes associated with hearing loss, such as Alport syndrome [ 1 ]. The presence of renal abnormalities, cardiac anomalies, and other syndromes should prompt evaluation of hearing [ 1 ].

Treatment and Management

For patients who develop end-stage renal disease, dialysis and kidney transplantation are treatment options [ 1 ]. Early diagnosis and treatment are crucial to delay kidney failure and manage associated hearing and vision problems [ 1 ]. Genetic counseling and regular monitoring are essential for optimal management of Alport syndrome.

From the Research

Definition and Characteristics of Alport Syndrome

• Alport syndrome is a rare genetic disease that results in disordered basement membrane type IV collagen, leading to ocular and auditory defects as well as progressive kidney disease 2.
• It is characterized by a defective glomerular basement membrane caused by mutations in type IV collagen genes COL4A3/A4/A5, resulting in defective type IV collagen α3, α4, or α5 chains 3.
• The syndrome has three different patterns of inheritance: X-linked, autosomal, and digenic 3.

Current Treatment Options

• Therapeutic blockade of the renin-angiotensin-aldosterone system can slow the progression to end-stage kidney disease (ESKD) 2.
• Renin-angiotensin-aldosterone system inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs), can significantly delay the progression of chronic kidney disease and the onset of ESRD 4, 5, 6.
• Ramipril, an ACEi, has been found to delay the onset of ESKD and is safe and effective in children and adolescents 3.

Novel Therapies and Potential Treatments

• Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been found to have additional properties that are nephroprotective, making them a potential candidate for treatment for those with other forms of progressive kidney disease, including Alport syndrome 2.
• However, the DAPA-CKD trial suggests that conclusions about the effectiveness of SGLT2 inhibitors in Alport syndrome cannot be extrapolated due to the small number of patients with Alport in the cohort 3.
• Other novel therapeutic targets under investigation include bardoxolone methyl, lademirsen, sparsentan, atrasentan, lipid-modifying agents, hydroxychloroquine, metformin, and paricalcitol 3.
• Future genomic therapeutic strategies such as chaperone therapy, genome editing, and stem cell therapy are also being explored 3, 5.