Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Practice Guideline
. 2025 May 30;40(6):1091-1106.
doi: 10.1093/ndt/gfae265.

Diagnosis, management and treatment of the Alport syndrome - 2024 guideline on behalf of ERKNet, ERA and ESPN

Roser Torra  1 , Beata Lipska-Zietkiewicz  2   3 , Frederic Acke  4 , Corinne Antignac  5 , Jan Ulrich Becker  6 , Emilie Cornec-Le Gall  7 , Albertien M van Eerde  8 , Nicolas Feltgen  9 , Rossella Ferrari  10 , Daniel P Gale  11 , Susie Gear  12 , Oliver Gross  13 , Stefanie Haeberle  14 , Laurence Heidet  15 , Rachel Lennon  16 , Laura Massella  17 , Kristina Pfau  18 , Maria Del Prado Venegas Pizarro  19 , Rezan Topaloglu  20 , Tanja Wlodkowski  14 , Heidi Zealey  12 ; ERKNet, ERA Genes&Kidney and ESPN Inherited renal disorders working group
Collaborators, Affiliations
Practice Guideline

Diagnosis, management and treatment of the Alport syndrome - 2024 guideline on behalf of ERKNet, ERA and ESPN

Roser Torra et al. Nephrol Dial Transplant. .

Abstract

Glomerular nephropathy resulting from the genetic defects in COL4A3/4/5 genes including the classical Alport syndrome is the second most common hereditary kidney disease characterized by persistent haematuria progressing to the need for kidney replacement therapy, frequently associated with sensorineural deafness, and occasionally with ocular anomalies. Diagnosis and management of COL4A3/4/5 glomerulopathy is a great challenge due to its phenotypic heterogeneity, multiple modes of inheritance, variable expressivity, and disease penetrance of individual variants as well as imperfect prognostic and progression factors and scarce and limited clinical trials, especially in children. As a joint initiative of the European Rare Kidney disease reference Network (ERKNet), European Renal Association (ERA Genes&Kidney), and European Society for Paediatric Nephrology (ESPN) Inherited renal disorders working group, a team of experts including adult and paediatric nephrologists, kidney geneticists, audiologists, ophthalmologists, and a kidney pathologist were selected to perform a systematic literature review on 21 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions. The experts formulated recommendations and formally graded them at a consensus meeting with input from patient representatives and a voting panel of nephrologists representing all regions of the world. Genetic diagnostics comprising joint analysis of COL4A3/4/5 genes is already the key diagnostic test during the initial evaluation of an individual presenting with persistent haematuria, proteinuria, kidney failure of unknown origin, focal segmental sclerosis of unknown origin, and possibly cystic kidney disease. Early renin-angiotensin system blockade is the standard of care therapy; sodium-glucose cotransporter-2 inhibitors may be added in adults with proteinuria and chronic kidney disease. Relatives with heterozygous COL4A3/4/5 variants should only be considered as the last possible resource for living kidney donation. This guideline provides guidance for the diagnosis and management of individuals with pathogenic variants in COL4A3/4/5 genes.

Keywords: COL4A3/4/5; Alport syndrome; collagen IV; glomerular basement membrane; haematuria.

PubMed Disclaimer

Conflict of interest statement

R.T. has given talks, acted as consultant or attended meetings organized by Genzyme-Sanofi, Takeda, Amicus, Orphan-Europe, Novartis, Alnylam, Chiesi, AstraZeneca, and Otsuka. R.T. is president of the European Renal Association. B.L.Z. has received speaker and/or consultant fees from Takeda, Novartis, and AstraZeneca. These were all unrelated to the topic of this guideline. D.P.G. has received speaker and/or consultancy fees from Novartis, Calliditas, Bayer, SOBI, Vifor, Sanofi, Alnylam. D.P.G. is supported by the St Peter's Trust for Kidney Bladder and Prostate research. O.G. received advisory fees from AstraZeneca, his employer received advisory fees from Boehringer Ingelheim. Employees from Boehringer Ingelheim and OG are co-inventors for the patent application EP3826642 (Empagliflozin for use in treating Alport syndrome). The other authors declare no competing interests.

References

    1. ClinGen Alport Syndrome Variant Curation Expert Panel Recommendations. https://www.clinicalgenome.org/affiliation/50146/ (8 April 2024, date last accessed).
    1. Savige J, Rana K, Tonna Set al. Thin basement membrane nephropathy. Kidney Int 2003;64:1169–78. 10.1046/j.1523-1755.2003.00234.x - DOI - PubMed
    1. Ouzzani M, Hammady H, Fedorowicz Zet al. Rayyan—a web and mobile app for systematic reviews. Syst Rev 2016;5:210. 10.1186/s13643-016-0384-4 - DOI - PMC - PubMed
    1. Classifying recommendations for clinical practice guidelines. Pediatrics 2004;114:874–7. 10.1542/peds.2004-1260 - DOI - PubMed
    1. Savige J, Gregory M, Gross Oet al. Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol 2013;24:364–75. 10.1681/ASN.2012020148 - DOI - PubMed

Publication types