Renal genetics in Australia: Kidney medicine in the genomic age

Abstract

There have been few new therapies for patients with chronic kidney disease in the last decade. However, the management of patients affected by genetic kidney disease is rapidly evolving. Inherited or genetic kidney disease affects around 10% of adults with end‐stage kidney disease and up to 70% of children with early onset kidney disease. Advances in next‐generation sequencing have enabled rapid and cost‐effective sequencing of large amounts of DNA. Next‐generation sequencing‐based diagnostic tests now enable identification of a monogenic cause in around 20% of patients with early‐onset chronic kidney disease. A definitive diagnosis through genomic testing may negate the need for prolonged diagnostic investigations and surveillance, facilitate reproductive planning and provide accurate counselling for at‐risk relatives. Genomics has allowed the better understanding of disease pathogenesis, providing prognostic information and facilitating development of targeted treatments for patients with inherited or genetic kidney disease. Although genomic testing is becoming more readily available, there are many challenges to implementation in clinical practice. Multidisciplinary renal genetics clinics serve as a model of how some of these challenges may be overcome. Such clinics are already well established in most parts of Australia, with more to follow in future. With the rapid pace of new technology and gene discovery, collaboration between expert clinicians, laboratory and research scientists is of increasing importance to maximize benefits to patients and health‐care systems.

Clinical impact of genomic testing in patients with suspected monogenic kidney disease

“…This challenge was foreseen prior to study commencement, and the multidisciplinary RGC model, which allowed support from a clinical geneticist and genetic counselor in reviewing all patients, was used to address this. 38 Our study has limitations. We did not consider the possible contribution of digenic inheritance or susceptibility alleles to the diagnostic yield in this cohort.…”

Diagnostic Yield of Next-Generation Sequencing in Patients With Chronic Kidney Disease of Unknown Etiology

“…This allows a more flexible analysis compared to gene panels and the opportunity to identify new causative genes. Furthermore, WES data can be stored for future reanalysis as new genes are discovered and variants are reclassified Jayasinghe et al, 2018). Although WES sequences the entire exome, it is possible to only target a specified subset of genes with an in silico panel (targeted WES).…”

“…Although WES sequences the entire exome, it is possible to only target a specified subset of genes with an in silico panel (targeted WES). This approach gives similar results as gene panels, but has the advantage that the original WES data can be "opened" for further analysis if new genes are discovered or if a causative variant cannot be identified in the initial analysis (Preston et al, 2017;Jayasinghe et al, 2018). Because of these advantages, most of the current diagnostic gene panels are based on targeted WES.…”

Attitudes and Practices of Australian Nephrologists Toward Implementation of Clinical Genomics

“…Genomic testing is becoming widely available as a diagnostic tool in nephrology 1 and evidence for clinical usefulness in the care of individuals with kidney disease is beginning to emerge [2][3][4] , with diagnostic yields ranging from 10 to 60% depending on patient selection strategies used. Funding for genetic and especially genomic testing is limited in many healthcare settings, and access to services such as genetic counseling and clinical genetics consultation is highly variable across many specialties, including nephrology [5][6][7] . Given the complexity of genetic kidney disease (GKD), in addition to the practical challenges associated with patient and test selection, result interpretation and counseling 6 , the nephrology workforce needs to be prepared and supported for diagnostic genomics to be effectively implemented.…”

“…Funding for genetic and especially genomic testing is limited in many healthcare settings, and access to services such as genetic counseling and clinical genetics consultation is highly variable across many specialties, including nephrology [5][6][7] . Given the complexity of genetic kidney disease (GKD), in addition to the practical challenges associated with patient and test selection, result interpretation and counseling 6 , the nephrology workforce needs to be prepared and supported for diagnostic genomics to be effectively implemented.…”