Thematic Area:  Alport Syndrome

The following guidance documents have been adopted based on standardized reviews and are followed in all ERKNet centers:

Consensus statement on standards and guidelines for the molecular diagnostics of Alport syndrome: refining the ACMG criteria

Eur J Hum Genet. 2021 Apr 15. doi: 10.1038/s41431-021-00858-1. Online ahead of print

Expert consensus guidelines for the genetic diagnosis of Alport syndrome

Pediatr Nephrol. 2019 Jul;34(7):1175-1189. doi: 10.1007/s00467-018-3985-4. Epub 2018 Jul 9.

Expert Guidelines for the Management of Alport Syndrome and Thin Basement Membrane Nephropathy

J Am Soc Nephrol 2013; 24:364-75

Core Recommendations:
  1. Genetic testing is the gold standard for the diagnosis of Alport syndrome and the demonstration of its mode of inheritance.
  2. All affected members of a family with X-linked Alport syndrome, including most mothers of affected males, should be identified and followed.
  3. Males with X-linked Alport syndrome and individuals with autosomal recessive disease should be treated with renin-angiotensin system blockade.
  4. Affected mothers of males with X-linked Alport syndrome should be discouraged from renal donation because of their own risk of kidney failure.
  5. Genetic testing should be considered in some individuals with thin basement membrane nephropathy to exclude X-linked Alport syndrome.
Comments by evaluators:
  • Useful and comprehensive guidelines.
  • The recommendations are described as expert opinions (Level D) / opinions of respected authorities (Level III). 
  • The health questions are specifically described and further categorised by sub types- Alport syndrome (X-Linked, autosomal recessive) and thin basement membrane nephropathy. 
  • The term autosomal dominant Alport syndrome is not discussed in these guidelines.

Clinical practice recommendations for the treatment of Alport syndrome: A statement of the Alport Syndrome Research Collaborative

 Pediatr Nephrol 2013; 28:5-11

 Core Recommendations:

  1. Monitoring for microalbuminuria and proteinuria should be initiated by age 1 year in at risk children, or as soon as a diagnosis of Alport syndrome is established, and repeated at least annually.
  2. Affected individuals with overt proteinuria (urine protein-creatinine ratio persistently > 0.2 mg/mg, or urinary protein excretion > 4 mg/m2/h in a timed collection) should receive treatment with ACE inhibitor therapy. 
  3. Treatment with ACE inhibitor therapy should be considered in affected boys with microalbuminuria in whom the risk of ESRD by age 30 is high.
  4. Second line treatment with an ARB (losartan) or aldosterone inhibition (spironolactone).

Comments by evaluators:

  • This guideline is for children with Alport syndrome.
  • Very little evidence. Mainly expert opinion. 
  • The authors of this manuscript are paediatric and adult nephrologists. Pharmacology and genetics input would be useful.