Lim Cynthia, Lim Ru Sin, Choo Jason, Leow Esther Huimin, Chan Gek Cher, Zhang Yaochun, Ng Jun Li, Chin Hui-Lin, Tan Ee Shien, Goh Jeannette, Gandhi Naline, Ng Yong Hong, Than Mya, Ganesan Indra, Chong Siew Le, Yap Celeste, Chao Sing Ming, Cham Breana, Kam Sylvia, Lim Jiin Ying, Mok Irene, Tan Hui Zhuan, Kwek Jia Liang, Lee Tung Lin, Wang Ziyin, Goh Su Mein, Lim Regina, Yeo See Cheng, Teo Boon Wee, Da Yi, Matchar David, Ng Kar Hui
Department of Renal Medicine, Medicine, Singapore General Hospital, SingHealth Duke-NUS Academic Medical Center, Singapore, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Am J Nephrol. 2025;56(2):158-171. doi: 10.1159/000542942. Epub 2024 Dec 3.
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.
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.
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.
单基因肾小球疾病的早期诊断和恰当治疗可减少肾衰竭，避免不必要的检查（如肾活检）以及免疫抑制剂的无效治疗，指导移植决策，并告知其家庭成员遗传风险。然而，新加坡对肾病的基因检测利用不足。我们旨在实施一项由肾病专家主导的基因服务，并评估新加坡单基因肾小球疾病基因检测的接受度、采用情况、效用和成本效益。
我们将进行一项前瞻性、多中心、II型混合有效性 - 实施研究，并采用事后设计来评估由肾病专家主导的针对疑似遗传性肾小球肾病的基因检测的实施情况和临床结果。多学科实施团队将培训“基因肾病专家”，以提供检测前和检测后的咨询，为疑似肾小球肾病（持续性镜下血尿和/或蛋白尿或白蛋白尿且无已知病因、激素抵抗性原发性肾病综合征、明显的家族性IgA肾病或无明显病因的慢性肾病）安排靶向外显子组测序，并解读基因检测结果；创建患者转诊、评估和管理的工作流程，并在定期的基因组委员会会议上讨论基因检测结果。结果包括患者和肾病专家的接受度、适宜性和采用情况、效用（接受基因检测并确诊为遗传性肾小球疾病的患者比例）以及成本效益。
本研究将创建并评估一项由肾病专家主导的基因服务，开发高效的变异筛选流程，并为新加坡单基因肾小球疾病的最佳转诊和基因检测策略提供未来建议。这将有助于基因检测在未来成为主流，从而在肾脏护理中实现精准医疗。
