Comprehensive evaluation of a prospective Australian patient cohort with suspected genetic kidney disease undergoing clinical genomic testing: a study protocol.

Jayasinghe K1,2,3,4,5, Stark Z3,5,6, Patel C3,7, Mallawaarachchi A3,8,9, McCarthy H3,10,11, Faull R3,12, Chakera A3,13, Sundaram M3,14, Jose M3,15,16, Kerr P1,2,4, Wu Y3,5,17, Wardrop L3,4,5, Goranitis I3,5,17, Best S3,5,18, Martyn M4,5,6, Quinlan C3,4,5,6,19, Mallett AJ20,5,21,22.

Author information

1: Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, Australia.
2: Monash University, Melbourne, Victoria, Australia.
3: Australian Genomics Health Alliance, Melbourne, Victoria, Australia.
4: Melbourne Genomics Health Alliance, Melbourne, Victoria, Australia.
5: Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
6: Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
7: Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
8: Department of Medical genomics, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
9: Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
10: Sydney Children's Hospitals Network, Sydney, New South Wales, Australia.
11: Children's Hospital Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia.
12: Royal Adelaide Hospital, Adelaide, South Australia, Australia.
13: Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
14: Royal Darwin Hospital, Darwin, Northern Territory, Australia.
15: School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
16: Royal Hobart Hospital, Hobart, Tasmania, Australia.
17: Health Economics Unit, Centre for Health Policy, University of Melbourne, Melbourne, Victoria, Australia.
18: Centre for Healthcare Resilience and Implementation Science, Australian Institute of Health Innovation, Macquarie University, Sydney, New South Wales, Australia.
19: Department of Paediatric Nephrology, Royal Children's Hospital, Melbourne, Victoria, Australia.
20: Australian Genomics Health Alliance, Melbourne, Victoria, Australia Andrew.Mallett@health.qld.gov.au.
21: Kidney Health Service and Conjoint Renal Research Laboratory, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
22: Institute for Molecular Bioscience and Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

Abstract

INTRODUCTION:

Recent advances in genomic technology have allowed better delineation of renal conditions, the identification of new kidney disease genes and subsequent targets for therapy. To date, however, the utility of genomic testing in a clinically ascertained, prospectively recruited kidney disease cohort remains unknown. The aim of this study is to explore the clinical utility and cost-effectiveness of genomic testing within a national cohort of patients with suspected genetic kidney disease who attend multidisciplinary renal genetics clinics.

METHODS AND ANALYSIS:

This is a prospective observational cohort study performed at 16 centres throughout Australia. Patients will be included if they are referred to one of the multidisciplinary renal genetics clinics and are deemed likely to have a genetic basis to their kidney disease by the multidisciplinary renal genetics team. The expected cohort consists of 360 adult and paediatric patients recruited by December 2018 with ongoing validation cohort of 140 patients who will be recruited until June 2020. The primary outcome will be the proportion of patients who receive a molecular diagnosis via genomic testing (diagnostic rate) compared with usual care. Secondary outcomes will include change in clinical diagnosis following genomic testing, change in clinical management following genomic testing and the cost-effectiveness of genomic testing compared with usual care.

ETHICS AND DISSEMINATION:

The project has received ethics approval from the Melbourne Health Human Research Ethics Committee as part of the Australian Genomics Health Alliance protocol: HREC/16/MH/251. All participants will provide written informed consent for data collection and to undergo clinically relevant genetic/genomic testing. The results of this study will be published in peer-reviewed journals and will also be presented at national and international conferences.