Diagnosis, management and treatment of the Alport syndrome – 2024 guideline on behalf of ERKNet, ERA and ESPN
Authors: Torra Roser , Lipska-Ziętkiewicz Beata , Acke Frederic , Antignac Corinne , Becker Jan Ulrich , Gall Emilie Cornec-Le , van Eerde Albertien M , Feltgen Nicolas , Ferrari Rosella , Gale Daniel P , Gross Oliver , Haeberle Stefanie , Wlodkowski Tanja , Heidet Laurence , Lennon Rachel , Massella Laura , Topaloglu Rezan , Pfau Kristina , del Prado Venegas Pizarro Maria , Zealey Heidi ,   ERKNet, ERA Genes&Kidney and ESPN WG Hereditary Kidney Disorders groups, Ailioaie Oana , Aksenova Marina , Barany Peter , Barua Moumita , Benetti Elisa , Bonebrake Lisa , Bonny Olivier , Bouts Antonia , Boyer Olivia , CaridiGalešić Ljubanović Gianluca , Alonso Castro-Cristina , Claes Kathleen , Conlon Peter , Claudiu George Costea , Decrameréphane St , Deltas Constantinos , Demir Erol , Demoulin Nathalie , Eijgelsheim Mark , Emma Francesco , Flinter Frances , Furlano Monica , Valentine Gillion Danica , Marta Ana Gomes , Haffner Dieter , Hoefele Julia , Pavlovic Jovicic Svetlana , Kashtan Clifford , Kohl Stefan , Konrad Martin , Kopač Matjaž , Lemoine Sandrine , Christoph Max Liebau , Lugani Francesca , Madrid Alvaro , Mallett Andrew , Mastrangelo Antonio , Meglič Anamarija , Meijer Esther , Miner Jeffrey , Mır Sevgı , Hui Kar Ng , Oliveiraão Paulo Jo , Vanessa Perez Maria Gomez , Maria Anna Pinto , Raes Ann , Rheault Michelle , Savige Judy , Schwarz Christoph , Manuel Sevillano Angel Prieto , Tantisattamo Ekamol , Tasic Velibor , Toryálmán K , Turner Neil , Weinstock Andre , Zakrocka Izabela 
Published: December 2024

Glomerular nephropathy resulting from the genetic defects in COL4A3/4/5 genes including the classical Alport syndrome (AS) is the second commonest hereditary kidney disease characterized by persistent haematuria progressing to the need of 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) Working Group Hereditary Kidney Disorders, 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 the key diagnostic test already 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.