The KIDNEYCODE Program: Diagnostic Yield and Clinical Features of Individuals with CKD

Area of Science:

• Nephrology
• Genetics
• Genomic Medicine

Background:

• Chronic kidney disease (CKD) increasingly recognized to have underlying genetic causes.
• Genetic testing for CKD remains underutilized despite its diagnostic potential.
• KIDNEYCODE program aimed to evaluate genetic testing's diagnostic yield in CKD.

Purpose of the Study:

• To evaluate the diagnostic yield of genetic testing in individuals with CKD.
• To characterize the phenotypic spectrum of genetic causes of CKD.
• To assess the utility of genetic testing within the KIDNEYCODE program.

Main Methods:

• Included 859 unrelated individuals undergoing panel testing (17 genes) via the KIDNEYCODE program.
• Eligibility criteria included eGFR ≤90 ml/min/1.73m² with hematuria or family history, or suspected/biopsy-confirmed Alport syndrome or FSGS.
• Analysis included individuals with and without kidney biopsies and those with prior clinical diagnoses.

Main Results:

• 234 individuals (27%) received molecular diagnoses, primarily for Alport syndrome (209), FSGS (12), and polycystic kidney disease (6).
• A positive family history of CKD was a stronger predictor of a positive genetic finding than clinical features alone.
• Among 248 individuals with kidney biopsies, 49 (20%) received a molecular diagnosis, predominantly in COL4A genes.

Conclusions:

• Genetic testing demonstrates significant diagnostic yield in individuals with CKD, particularly for Alport syndrome.
• Family history is a crucial factor in identifying individuals likely to benefit from genetic testing for CKD.
• Findings support expanding access to genetic testing for CKD patients, especially those with family history, hematuria, or hearing loss.