Dr Julia Jefferis1,2, Dr Sadia Jahan2,3, Dr Ulf Schmitz2, Dr Erik Biros2, Dr Zornitza Stark4,5,6, Dr Amali Mallawaarachchi7,8,9,10, Dr Chirag Patel11, Dr Andrew Mallett2,12,13
1Department of Nephrology, Mater Hospital, Brisbane, Australia, 2College of Medicine and Dentistry, James Cook University, Townsville, Australia, 3Royal Adelaide Hospital, Brisbane, Australia, 4Australian Genomics, Murdoch Children’s Research Institute, Melbourne, Australia, 5 Victorian Clinical Genetics Services, Murdoch Children’s Research Institute,, Melbourne, Australia, 6University of Melbourne, Melbourne, Australia, 7Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research, , Sydney, Australia, 8Clinical Genetics Service, Institute of Precision Medicine and Bioinformatics and Institute of Academic Medicine, Royal Prince Alfred Hospital, Sydney, Australia, 9School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, Australia, 10Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia, 11Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia, 12Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia, 13Department of Renal Medicine, Townsville University Hospital, Douglas, Australia
Biography:
Dr Julia Jefferis is a nephrologist currently undertaking a PhD in genetic kidney disease.
Introduction:
Kidney disease of uncertain cause (UKD) is increasingly recognised as due to an underlying genetic basis. We conducted a systematic review to evaluate diagnostic yield of genetic testing in UKD.
Methods:
A PROSPERO registered systematic review was undertaken in compliance with PRISMA, identifying papers which undertook genetic testing in patients with UKD, searching OVID, Embase and Scopus databases. Inclusion criteria were patients with chronic kidney disease, where the aetiology was considered uncertain, who underwent genetic testing (panel/whole exome/genome sequencing). Patient demographics, details of kidney disease, urinalysis, biopsy, imaging, ancestry, family history and genetic test results were extracted. Outcomes of interest were demographics, diagnostic rate and genotype.
Findings:
Initial searches identified 288 papers for full text review with 51 undergoing full text analysis and 48 suitable for analysis. From 22,618 patients, a cohort of 4,632 were determined to have UKD, and the median diagnostic yield was 28.6% (IQR 17-34%). In this cohort 73.4% were of European ancestry, median age was 34 years, 42% were female gender, 40% had a family history of kidney disease and 70.9% were undergoing kidney replacement therapy. Testing strategies included single gene testing (3), panel testing (22), whole exome (19) and whole genome (5). Those receiving a diagnosis (N=669) with pathogenic and/or likely pathogenic variants were extracted for further analysis; over one hundred genes were implicated, though seven accounted for the majority of diagnoses COL4A3-5 (179), NPHP1-4 (82), UMOD (34), PAX2 (28), INF2 (18), PKD1(17), and MUC1 (12).
Conclusion:
The diagnostic rate of 28.6% in this meta-analysis suggests that patients with uncertain aetiology of kidney disease should be assessed for genetic forms of kidney disease including with genomic testing.
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