Clinical implementation of Nephrologist-led Genomic Testing for Glomerular Diseases in Singapore: Rationale and Protocol.

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 under-utilized 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-center, 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.