The importance of clinician, patient and researcher collaborations in Alport syndrome

Abstract

Alport syndrome is caused by mutations in the genes COL4A3, COL4A4 or COL4A5 and is characterised by progressive glomerular disease, sensorineural hearing loss and ocular defects. Occurring in less than 1:5000, Alport syndrome is a rare genetic disorder but still accounts for > 1% of the prevalent population receiving renal replacement therapy. There is also increasing awareness about the risk of chronic kidney disease in individuals with heterozygous mutations in Alport syndrome genes. The mainstay of current therapy is the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, yet potential new therapies are now entering clinical trials. The 2017 International Workshop on Alport Syndrome in Glasgow was a pre-conference workshop ahead of the 50th anniversary meeting of the European Society for Pediatric Nephrology. It focussed on updates in clinical practice, genetics and basic science and also incorporated patient perspectives. More than 80 international experts including clinicians, geneticists, researchers from academia and industry, and patient representatives took part in panel discussions and breakout groups. This report summarises the workshop proceedings and the relevant contemporary literature. It highlights the unique clinician, patient and researcher collaborations achieved by regular engagement between the groups.

Keywords: Alport syndrome; Basement membrane; COL4A3; COL4A4; COL4A5; Type IV collagen.

Fig. 1

Clinical care in Alport syndrome. The presentations covered patient registries, precision medicine, genetic screening and clinical trials

Fig. 2

Diagnosis and genetics. The importance of education and raising awareness was discussed together with the classification of Alport syndrome. Genomic sequencing projects such as 100,000 (100 k) genomes in the UK will help inform about the frequency of Alport gene mutations

Fig. 3

Basic science. The presentation covered the different experimental systems in use to investigate the biology of type IV collagen and basement membranes. There was a focus on the mechanisms of hearing loss in Alport syndrome

Fig. 4

Factors that influence the progression of Alport syndrome. Treatments that have confirmed or proposed effects on protecting kidney function, cardiovascular risk and hearing (top half in green) and factors that are known or thought to be deleterious (bottom half in blue). ACE angiotensin-converting enzyme, ARB angiotensin receptor blocker, HMG-CoA β-hydroxy β-methylglutaryl-CoA, NSAIDs non-steroidal anti-inflammatory drugs

Fig. 5

Patient perspective. Four presentations from members of Alport syndrome patient organisations highlighted the importance of the patient voice