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. 2025;56(2):158-171.
doi: 10.1159/000542942. Epub 2024 Dec 3.

Clinical Implementation of Nephrologist-Led Genomic Testing for Glomerular Diseases in Singapore: Rationale and Protocol

Cynthia Lim  1   2 , Ru Sin Lim  3 , Jason Choo  1 , Esther Huimin Leow  4 , Gek Cher Chan  5 , Yaochun Zhang  6 , Jun Li Ng  6 , Hui-Lin Chin  6 , Ee Shien Tan  7 , Jeannette Goh  7 , Naline Gandhi  8 , Yong Hong Ng  4 , Mya Than  6 , Indra Ganesan  4 , Siew Le Chong  4 , Celeste Yap  4 , Sing Ming Chao  4 , Breana Cham  7 , Sylvia Kam  7 , Jiin Ying Lim  7 , Irene Mok  1 , Hui Zhuan Tan  1 , Jia Liang Kwek  1 , Tung Lin Lee  1 , Ziyin Wang  3 , Su Mein Goh  3 , Regina Lim  3 , See Cheng Yeo  3 , Boon Wee Teo  9 , Yi Da  9 , David Matchar  8   10 , Kar Hui Ng  6
Affiliations

Clinical Implementation of Nephrologist-Led Genomic Testing for Glomerular Diseases in Singapore: Rationale and Protocol

Cynthia Lim et al. Am J Nephrol. 2025.

Abstract

Introduction: The early diagnosis and appropriate treatment of monogenic glomerular diseases can reduce kidney failure, avoid unnecessary investigations such as kidney biopsies and ineffective treatment with immunosuppressants, guide transplant decisions, and inform the genetic risks of their family members. Yet, genetic testing for kidney disease is underutilized in Singapore. We aimed to implement a nephrologist-led genetic service and evaluate the acceptance, adoption, utility, and cost-effectiveness of genetic testing for monogenic glomerular disease in Singapore.

Methods: We will perform a prospective, multi-centre, type II hybrid effectiveness-implementation study with a post-design to evaluate both implementation and clinical outcomes of nephrologist-led genetic testing for suspected genetic glomerular kidney diseases. The multi-disciplinary implementation team will train "genetic nephrologists" to provide pre- and post-test counselling, order targeted exome panel sequencing for suspected glomerular kidney diseases (persistent microscopic haematuria and/or albuminuria or proteinuria in the absence of known causes, steroid-resistant primary nephrotic syndrome, apparent familial IgA nephropathy, or chronic kidney disease with no apparent cause), and interpret genetic test results; create workflows for patient referral, evaluation and management, and discuss genetic results at regular genomic board meetings. The outcomes are acceptance, appropriateness and adoption among patients and nephrologists, utility (proportion of patients who received genetic testing and have a confirmed diagnosis of genetic glomerular disease), and cost-effectiveness.

Conclusion: This study will create and evaluate a nephrologist-led genetic service, develop an efficient variant curation process, and inform future recommendations on the optimal referral and genetic testing strategy for monogenic glomerular disease in Singapore. This will facilitate the future mainstreaming of genetic testing that will enable precision medicine in kidney care.

Keywords: Genomic test; Glomerulonephritis; Implementation science; Rare kidney disease.

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Conflict of interest statement

Cynthia Lim received honoraria from AstraZeneca, Boehringer Ingelheim, and Sebia. Jason Choo has received consulting fees from Novartis, Bayer, AstraZeneca, Boehringer Ingelheim, Pfizer, Nitto Denko ATC, GSK, and Baxter; speaker bureau fees from Abbott, Bayer, AstraZeneca, and Boehringer Ingelheim; participation on Data Safety Monitoring Boards for Novartis; and scientific grant funding from National Medical Research Council Singapore and Nitto Denko ATC and is the President of the Singapore Society of Nephrology and Medical Director of the National Kidney Foundation, Singapore; Gek Cher Chan received research funding from National University Health System and National Medical Research Council Singapore; Hui Zhuan Tan received honoraria from AstraZeneca, Boehringer Ingelheim, and Johnson & Johnson; Hui-Lin Chin has shares in Alamya Health; Jia Liang Kwek has received honoraria from AstraZeneca, Boehringer Ingelheim, Otsuka, Lien Centre for Palliative Care, Singapore Institute of Technology and Nanyang Polytechnic and research funding from the National Kidney Foundation, Singapore; and the remaining authors have no conflicts of interest to declare.

Figures

Fig. 1.
Fig. 1.
Potential barriers to genetic testing for glomerular diseases and potential strategies to address the barriers.
Fig. 2.
Fig. 2.
Logic model for the complex implementation of genetic services by nephrologists.
See this image and copyright information in PMC

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