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Clinical utility of genomics in genetic kidney disease

Clinical utility of genomics in genetic kidney disease

Background

Melbourne Genomics’ Clinical Flagships have been at the forefront of determining when genomic testing makes a demonstrable difference to the safety and quality of patient care; genetic kidney disease (GKD) is one of 16 areas of health investigated.

Genetic kidney disease affects about 3% of the Australian population. One in seven adult Australians have chronic kidney disease and up to 20% of this may be genetic in origin.

Although there is no cure, early identification and proactive treatment may slow the progression of genetic kidney disease and delay the need for dialysis and kidney transplantation.

Publications

"Clinical impact of genomic testing in patients with suspected monogenic kidney disease", Kushani Jayasinghe, Zornitza Stark, Peter G. Kerr, Clara Gaff, Melissa Martyn, John Whitlam, Belinda Creighton, Elizabeth Donaldson, Matthew Hunter, Anna Jarmolowicz, Lilian Johnstone, Emma Krzensinski, Sebastian Lunke, Elly Lynch, Kathleen Nicholls, Chirag Patel, Yael Prawer, Jessica Ryan, Emily J. See, Andrew Talbot, Alison Trainer, Rigan Tytherleigh, Giulia Valente, Matthew Wallis, Louise Wardrop, Kirsty H. West, Susan M. White, Ella Wilkins, Andrew J. Mallet and Catherine Quinlan, Genetics in Medicine (2020) https://doi.org/10.1038/s41436-020-00963-4

Project description

The objective: to determine if genomic sequencing can provide a more definitive diagnosis and enable more personalised care for children and adults with GKD.

The Genetic Kidney Disease Flagship was led by Dr Catherine Quinlan (The Royal Children’s Hospital). Key coordination was provided by Dr Andrew Talbot (The Royal Melbourne Hospital), Dr John Whitlam (Austin Health) and Dr Jessica Ryan (Monash Health); more than 20 health professionals were directly involved1.

Activities

Between April 2017 and October 2018, nephrologists referred patients for assessment and testing. A total of 204 patients received genomic testing through the Flagship.

Analysis was generally targeted to genes known to be involved in GKD; analysis of a wider set of disease-causing genes was offered in a limited number of cases (primarily complex patients).

Outcomes

Of the patients tested, 80 (39%) received a diagnosis, 31 of whom had their diagnosis completely reclassified.

Genomic testing had profound implications for care, with 59% of those diagnosed experiencing a change in medical management, including other planned testing no longer being required. A planned renal biopsy was no longer required for 10 (13%) patients who received a genomic diagnosis. Other changes to patient care included alterations in medical monitoring (44%) and treatment plans (20%), as well as other specific actions such as bringing forward kidney transplantation and informing family planning (9%).

Lessons learnt

  • Genomic sequencing changed or clarified diagnosis for a third of all patients tested. A definitive genomic diagnosis was made for 39% of patients, none of which would have been made using the usual testing available at the time the study began.
  • Education and support from clinical geneticists enabled nephrologists to make appropriate use of genomic testing. The diagnostic utility achieved in this study is higher than in published studies that did not involve multidisciplinary assessment of referrals. Funding to support multidisciplinary assessment for kidney patients is required to ensure appropriate use of genomic testing.

Impact

Evidence generated by the Flagship enabled the national KidGen network to receive philanthropic funding to continue offering a multidisciplinary renal genetics service.

As a result of Flagship findings, pathology departments at two member hospitals are now considering requests for genomic testing from within their existing budget.

Clinical Flagship team




Name

Organisation

Role

Catherine Quinlan

RCH

Paediatric nephrologist

Andrew Talbot

RMH

Nephrologist

John Whitlam

Austin Health

Nephrologist

Jessica Ryan

Monash Health

Nephrologist

Kushani Jayasinghe Monash Health Nephrologist

Alison Trainer

RMH

Clinical geneticist

Anna Jarmolowicz

RMH

Genetic counsellor

Belinda Creighton

Monash Health

Genetic counsellor

Ella Wilkins

VCGS

Genetic counsellor

Emma Krzesinski

Monash Health

Clinical geneticist

Giulia Valente

Austin Health

Genetic counsellor

Heather Chalinor

Austin Health

Genetic counsellor

Ingrid Winship

RMH

Clinical geneticist

Kathy Nicholls

RMH

Nephrologist

Kirsty West

RMH

Genetic counsellor

Lilian Johnstone

Monash Health

Paediatric nephrologist

Louise Wardrop

Australian Genomics

Program manager

Mathew Wallis

Austin Health

Clinical geneticist

Matthew Hunter

Monash Health

Clinical geneticist

Sue White

VCGS

Clinical geneticist

Yael Prawer

Monash Health

Genetic counsellor

Zornitza Stark

VCGS

Clinical geneticist

The health economic evaluation for this Flagship was led by Ilias Goranitis from the University of Melbourne.
 

1 The Melbourne Genomics Genetic Kidney Disease Flagship is part of a broader Australian network of nephrologists, KidGen, which has project coordinator funding from Australian Genomics.