Enhancing diagnostic outcomes in kidney genetic disorders: the KidGen national kidney genomics study protocol

Amali Mallawaarachchi; Hugh McCarthy; Thomas A. Forbes; Kushani Jayasinghe; Chirag Patel; Stephen I. Alexander; Tiffany Boughtwood; Jeffrey Braithwaite; Aron Chakera; Sam Crafter; Ira W. Deveson; Randall Faull; Trudie Harris; Lilian Johnstone; Matthew Jose; Anna Leaver; Melissa H. Little; Daniel MacArthur; Tessa Mattiske; Christine Mincham; Kathy Nicholls; Catherine Quinlan; Michael C. J. Quinn; Gopala Rangan; Jessica  Ryan; Cas Simons; Ian Smyth; Madhivanan Sundaram; Peter Trnka; Laura Wedd; Erik Biros; Zornitza Stark; Andrew Mallett

doi:10.1186/s12882-024-03926-y

Enhancing diagnostic outcomes in kidney genetic disorders: the KidGen national kidney genomics study protocol

Amali Mallawaarachchi, Hugh McCarthy, Thomas A. Forbes, Kushani Jayasinghe, Chirag Patel, Stephen I. Alexander, Tiffany Boughtwood, Jeffrey Braithwaite, Aron Chakera, Sam Crafter, Ira W. Deveson, Randall Faull, Trudie Harris, Lilian Johnstone, Matthew Jose, Anna Leaver, Melissa H. Little, Daniel MacArthur, Tessa Mattiske, Christine MinchamKathy Nicholls, Catherine Quinlan, Michael C. J. Quinn, Gopala Rangan, Jessica Ryan, Cas Simons, Ian Smyth, Madhivanan Sundaram, Peter Trnka, Laura Wedd, Erik Biros, Zornitza Stark, Andrew Mallett

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Abstract

Background: Genetic kidney disease (GKD) significantly affects the community and is responsible for a notable portion of adult kidney disease cases and about half of cases in paediatric patients. It substantially impacts the quality of life and life expectancy for affected children and adults across all stages of kidney disease. Precise genetic diagnosis in GKD promises to improve patient outcomes, provide access to targeted treatments, and reduce the disease burden for individuals, families, and healthcare systems. Genetic investigations are increasingly used in nephrology practice; however, many patients who undergo testing still lack a definitive diagnosis.

Methods: The KidGen National Kidney Genomics Study aims to increase diagnostic yield for those with suspected monogenic kidney disease without a diagnosis after standard diagnostic genetic testing. The program will seek to enrol up to 200 families from KidGen Collaborative kidney genetics clinics across Australia who have yet to receive conclusive diagnoses despite prior testing. Participants will undergo a personalised pathway of research genomic investigations. These include re-analysing existing data and/or undergoing advanced genomic testing methods, including short and long-read whole-genome sequencing, RNA sequencing, and functional genomics strategies using mouse modelling or kidney organoids.

Discussion: The KidGen National Kidney Genomics Study is a coordinated, multidisciplinary extension of previous research projects that aims to assess the diagnostic yield of advanced genomic approaches. The study's evidence will drive changes to current diagnostic pathways, including identifying which chronic kidney disease patients are most likely to benefit from a more comprehensive genomic approach to diagnosis.

Original language	English
Article number	51
Pages (from-to)	1-11
Number of pages	11
Journal	BMC Nephrology
Volume	26
Issue number	1
DOIs	https://doi.org/10.1186/s12882-024-03926-y
Publication status	Published - 3 Feb 2025

Bibliographical note

Copyright the Author(s) 2025. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

Diagnostic yield
Undiagnosed patients
Study protocol
Re-analysis
Advanced genomic testing
Genetic kidney disease

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10.1186/s12882-024-03926-yLicence: CC BY-NC-ND

Publisher version (open access)Final published version, 1.52 MBLicence: CC BY-NC-ND

Cite this

Mallawaarachchi, A., McCarthy, H., Forbes, T. A., Jayasinghe, K., Patel, C., Alexander, S. I., Boughtwood, T., Braithwaite, J., Chakera, A., Crafter, S., Deveson, I. W., Faull, R., Harris, T., Johnstone, L., Jose, M., Leaver, A., Little, M. H., MacArthur, D., Mattiske, T., ... Mallett, A. (2025). Enhancing diagnostic outcomes in kidney genetic disorders: the KidGen national kidney genomics study protocol. BMC Nephrology, 26(1), 1-11. Article 51. https://doi.org/10.1186/s12882-024-03926-y

@article{e1b527aa41574603a05d7bf05d6be21c,

title = "Enhancing diagnostic outcomes in kidney genetic disorders: the KidGen national kidney genomics study protocol",

abstract = "Background: Genetic kidney disease (GKD) significantly affects the community and is responsible for a notable portion of adult kidney disease cases and about half of cases in paediatric patients. It substantially impacts the quality of life and life expectancy for affected children and adults across all stages of kidney disease. Precise genetic diagnosis in GKD promises to improve patient outcomes, provide access to targeted treatments, and reduce the disease burden for individuals, families, and healthcare systems. Genetic investigations are increasingly used in nephrology practice; however, many patients who undergo testing still lack a definitive diagnosis. Methods: The KidGen National Kidney Genomics Study aims to increase diagnostic yield for those with suspected monogenic kidney disease without a diagnosis after standard diagnostic genetic testing. The program will seek to enrol up to 200 families from KidGen Collaborative kidney genetics clinics across Australia who have yet to receive conclusive diagnoses despite prior testing. Participants will undergo a personalised pathway of research genomic investigations. These include re-analysing existing data and/or undergoing advanced genomic testing methods, including short and long-read whole-genome sequencing, RNA sequencing, and functional genomics strategies using mouse modelling or kidney organoids. Discussion: The KidGen National Kidney Genomics Study is a coordinated, multidisciplinary extension of previous research projects that aims to assess the diagnostic yield of advanced genomic approaches. The study's evidence will drive changes to current diagnostic pathways, including identifying which chronic kidney disease patients are most likely to benefit from a more comprehensive genomic approach to diagnosis.",

keywords = "Diagnostic yield, Undiagnosed patients, Study protocol, Re-analysis, Advanced genomic testing, Genetic kidney disease",

author = "Amali Mallawaarachchi and Hugh McCarthy and Forbes, \{Thomas A.\} and Kushani Jayasinghe and Chirag Patel and Alexander, \{Stephen I.\} and Tiffany Boughtwood and Jeffrey Braithwaite and Aron Chakera and Sam Crafter and Deveson, \{Ira W.\} and Randall Faull and Trudie Harris and Lilian Johnstone and Matthew Jose and Anna Leaver and Little, \{Melissa H.\} and Daniel MacArthur and Tessa Mattiske and Christine Mincham and Kathy Nicholls and Catherine Quinlan and Quinn, \{Michael C. J.\} and Gopala Rangan and Jessica Ryan and Cas Simons and Ian Smyth and Madhivanan Sundaram and Peter Trnka and Laura Wedd and Erik Biros and Zornitza Stark and Andrew Mallett",

note = "Copyright the Author(s) 2025. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2025",

month = feb,

day = "3",

doi = "10.1186/s12882-024-03926-y",

language = "English",

volume = "26",

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Mallawaarachchi, A, McCarthy, H, Forbes, TA, Jayasinghe, K, Patel, C, Alexander, SI, Boughtwood, T, Braithwaite, J, Chakera, A, Crafter, S, Deveson, IW, Faull, R, Harris, T, Johnstone, L, Jose, M, Leaver, A, Little, MH, MacArthur, D, Mattiske, T, Mincham, C, Nicholls, K, Quinlan, C, Quinn, MCJ, Rangan, G, Ryan, J, Simons, C, Smyth, I, Sundaram, M, Trnka, P, Wedd, L, Biros, E, Stark, Z & Mallett, A 2025, 'Enhancing diagnostic outcomes in kidney genetic disorders: the KidGen national kidney genomics study protocol', BMC Nephrology, vol. 26, no. 1, 51, pp. 1-11. https://doi.org/10.1186/s12882-024-03926-y

TY - JOUR

T1 - Enhancing diagnostic outcomes in kidney genetic disorders

T2 - the KidGen national kidney genomics study protocol

AU - Mallawaarachchi, Amali

AU - McCarthy, Hugh

AU - Forbes, Thomas A.

AU - Jayasinghe, Kushani

AU - Patel, Chirag

AU - Alexander, Stephen I.

AU - Boughtwood, Tiffany

AU - Braithwaite, Jeffrey

AU - Chakera, Aron

AU - Crafter, Sam

AU - Deveson, Ira W.

AU - Faull, Randall

AU - Harris, Trudie

AU - Johnstone, Lilian

AU - Jose, Matthew

AU - Leaver, Anna

AU - Little, Melissa H.

AU - MacArthur, Daniel

AU - Mattiske, Tessa

AU - Mincham, Christine

AU - Nicholls, Kathy

AU - Quinlan, Catherine

AU - Quinn, Michael C. J.

AU - Rangan, Gopala

AU - Ryan, Jessica

AU - Simons, Cas

AU - Smyth, Ian

AU - Sundaram, Madhivanan

AU - Trnka, Peter

AU - Wedd, Laura

AU - Biros, Erik

AU - Stark, Zornitza

AU - Mallett, Andrew

N1 - Copyright the Author(s) 2025. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2025/2/3

Y1 - 2025/2/3

N2 - Background: Genetic kidney disease (GKD) significantly affects the community and is responsible for a notable portion of adult kidney disease cases and about half of cases in paediatric patients. It substantially impacts the quality of life and life expectancy for affected children and adults across all stages of kidney disease. Precise genetic diagnosis in GKD promises to improve patient outcomes, provide access to targeted treatments, and reduce the disease burden for individuals, families, and healthcare systems. Genetic investigations are increasingly used in nephrology practice; however, many patients who undergo testing still lack a definitive diagnosis. Methods: The KidGen National Kidney Genomics Study aims to increase diagnostic yield for those with suspected monogenic kidney disease without a diagnosis after standard diagnostic genetic testing. The program will seek to enrol up to 200 families from KidGen Collaborative kidney genetics clinics across Australia who have yet to receive conclusive diagnoses despite prior testing. Participants will undergo a personalised pathway of research genomic investigations. These include re-analysing existing data and/or undergoing advanced genomic testing methods, including short and long-read whole-genome sequencing, RNA sequencing, and functional genomics strategies using mouse modelling or kidney organoids. Discussion: The KidGen National Kidney Genomics Study is a coordinated, multidisciplinary extension of previous research projects that aims to assess the diagnostic yield of advanced genomic approaches. The study's evidence will drive changes to current diagnostic pathways, including identifying which chronic kidney disease patients are most likely to benefit from a more comprehensive genomic approach to diagnosis.

AB - Background: Genetic kidney disease (GKD) significantly affects the community and is responsible for a notable portion of adult kidney disease cases and about half of cases in paediatric patients. It substantially impacts the quality of life and life expectancy for affected children and adults across all stages of kidney disease. Precise genetic diagnosis in GKD promises to improve patient outcomes, provide access to targeted treatments, and reduce the disease burden for individuals, families, and healthcare systems. Genetic investigations are increasingly used in nephrology practice; however, many patients who undergo testing still lack a definitive diagnosis. Methods: The KidGen National Kidney Genomics Study aims to increase diagnostic yield for those with suspected monogenic kidney disease without a diagnosis after standard diagnostic genetic testing. The program will seek to enrol up to 200 families from KidGen Collaborative kidney genetics clinics across Australia who have yet to receive conclusive diagnoses despite prior testing. Participants will undergo a personalised pathway of research genomic investigations. These include re-analysing existing data and/or undergoing advanced genomic testing methods, including short and long-read whole-genome sequencing, RNA sequencing, and functional genomics strategies using mouse modelling or kidney organoids. Discussion: The KidGen National Kidney Genomics Study is a coordinated, multidisciplinary extension of previous research projects that aims to assess the diagnostic yield of advanced genomic approaches. The study's evidence will drive changes to current diagnostic pathways, including identifying which chronic kidney disease patients are most likely to benefit from a more comprehensive genomic approach to diagnosis.

KW - Diagnostic yield

KW - Undiagnosed patients

KW - Study protocol

KW - Re-analysis

KW - Advanced genomic testing

KW - Genetic kidney disease

UR - https://www.scopus.com/pages/publications/85217877374

U2 - 10.1186/s12882-024-03926-y

DO - 10.1186/s12882-024-03926-y

M3 - Article

C2 - 39901087

SN - 1471-2369

VL - 26

SP - 1

EP - 11

JO - BMC Nephrology

JF - BMC Nephrology

IS - 1

M1 - 51

ER -

Enhancing diagnostic outcomes in kidney genetic disorders: the KidGen national kidney genomics study protocol

Abstract

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Keywords

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