Kidney Week

Abstract: FR-PO668

Diagnostic Yield and Clinical Utility of Genomic Testing in Patients with Suspected Genetic Kidney Disease: Singapore's First-Year Experience

Session Information

• Genetic Kidney Diseases: Cohort Studies - Genetic Associations and Diagnoses
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Lim, Ru Sin, Tan Tock Seng Hospital, Singapore, Singapore

Ru Sin Lim, MBBS

• Lim, Regina Shaoying, Tan Tock Seng Hospital, Singapore, Singapore

Regina Shaoying Lim, MBBS

• Wang, Ziyin, Tan Tock Seng Hospital, Singapore, Singapore

Ziyin Wang

• Zhang, Yaochun, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore

Yaochun Zhang, PhD

• Lim, Si Ting, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore

Si Ting Lim

• Than, Mya, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore

Mya Than, MBBS, MPH

• Ng, Jun Li, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore

Jun Li Ng

• Chong, Kay Yuan, Singapore General Hospital, Singapore, Singapore

Kay Yuan Chong, MPH

• Ho, Jing Yi, KK Women's and Children's Hospital, Singapore, Singapore, Singapore

Jing Yi Ho

• Leow, Esther Huimin, KK Women's and Children's Hospital, Singapore, Singapore, Singapore

Esther Huimin Leow, MBBS

• Ng, Yong Hong, KK Women's and Children's Hospital, Singapore, Singapore, Singapore

Yong Hong Ng, MBBS

• Choo Chon Jun, Jason, Singapore General Hospital, Singapore, Singapore

Jason Choo Chon Jun, MBBS, FASN

• Chan, Gek Cher, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore

Gek Cher Chan, MBChB

• Da, Yi, National University Health System, Singapore, Singapore, Singapore

Yi Da, MD

• Du, Ruochen, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore

Ruochen Du

• Ng, Kar Hui, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore

Kar Hui Ng, MBBS

Group or Team Name

• Renal Alliance for Precision Diagnosis in Singapore (RAPIDS).

Background

The genetic diagnostic yield for monogenic kidney disease is 25-30% in children and 10-30% in adults. Recognizing genetic kidney disease (GKD) as a cause of chronic kidney disease (CKD) has clinical implications. We aim to evaluate the diagnostic yield and clinical utility of genomic testing in suspected GKD patients.

Methods

We included patients with primary glomerular diseases with suspected genetic etiology or CKD of unknown etiology. Proband samples underwent clinical-grade targeted panel testing of 84 glomerular genes or whole exome sequencing (WES). This study was conducted at four tertiary hospitals in Singapore from March 2023 to January 2024.

Results

We recruited 147 probands: 102 (69.4%) adults and 45 (30.6%) children, with 61 (41.5%) females. The mean recruitment age was 33.1 ± 18.4 years and the mean disease onset age was 24.5 ± 17.4 years. They comprised of 118 (80.2%) Chinese, 12 (8.2%) Malays and 10 (6.8%) Indians. The genetic diagnostic rate was 34/147 (23.1%): 12/45 (26.7%) in children and 22/102 (21.6%) in adults involving ten distinct disorders, of which Alport syndrome accounts for 76%. 4 probands (2.7%) had suspicious variants of uncertain significance. Female gender (OR 6.7; p=0.001), extrarenal malformations (OR 3.5; p=0.039), and Alport features on kidney biopsy (OR 17.7; p=0.029) predict a GKD diagnosis. Of those with GKD diagnosis who had post-genetic counselling (n=26), genomic testing had significant clinical impact in 20/26 (77%), entailing providing appropriate treatment in 13/26 (50%), avoiding kidney biopsy in 5/26 (19.2%), initiating extra-renal surveillance in 10/26 (38.5%), confirming the genetic diagnosis, offering closure and prognostication in 16/26 (61.5%), guiding reproductive decisions in 9/26 (34.6%), offering cascade family testing in 14/26 (53.8%), and aiding in selecting suitable living kidney donor while predicting post-transplant recurrence in 4/26 (15.4%).

Conclusion

Our study shows that genomic testing has a high diagnostic yield, impacting patient management for both positive and negative findings. This supports integrating genomic testing into standard kidney disease care and underscores its clinical utility in suspected GKD.

Funding

• Government Support – Non-U.S.