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Abstract: PO1612

KIDNEYCODE: A Genetic Testing Program for Patients with CKD

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Devarajan, Prasad, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Appel, Gerald B., Columbia University Irving Medical Center, New York, New York, United States
  • Block, Geoffrey A., US Renal Care Inc., Plano, Texas, United States
  • Lieberman, Kenneth V., Hackensack University Medical Center, Hackensack, New Jersey, United States
  • McCalley, Stephen, Reata Pharmaceuticals Inc, Irving, Texas, United States
  • McKay, Jim, Reata Pharmaceuticals Inc, Irving, Texas, United States
  • Meyer, Colin John, Reata Pharmaceuticals Inc, Irving, Texas, United States
  • Warady, Bradley A., University of Missouri Kansas City, Kansas City, Missouri, United States
  • Chang, Alex R., Kidney Health Research Institute, Geisinger Medical Center, Danville, Pennsylvania, United States
  • Robinson, Kristina A., Invitae Corporation, San Francisco, California, United States
Background

The International Society of Nephrology recommends the adoption of genetic testing with a goal of providing precision medicine based on individual risk. A recent whole-exome sequencing study showed that genetic inheritance may be responsible for up to 10% of CKD diagnoses. We designed a gene panel to prospectively provide genetic testing in a subset of patients with CKD.

Methods

Reata Pharmaceuticals is partnering with Invitae on KIDNEYCODE, a US program that provides no-charge genetic testing using next generation sequencing (NGS) to enable diagnosis of a subset of rare monogenic causes of CKD: Alport syndrome (AS), autosomal dominant polycystic kidney disease (ADPKD) due to PKD2 variants, focal segmental glomerulosclerosis (FSGS), and autosomal recessive PKD due to PKHD1 variants. Invitae’s renal disease panel includes 17 genes (ACTN4, ANLN, CD2AP, COL4A3, COL4A4, COL4A5, CRB2, HNF1A, INF2, LMX1B, MYO1E, NPHS1, NPHS2, PAX2, PKD2, PKHD1, and TRPC6). Patients at risk for hereditary CKD (eGFR ≤ 90 mL/min/1.73m2 plus hematuria or a family history of CKD) or known or suspected AS or FSGS are eligible. Family members of those with known or suspected AS or FSGS are also eligible.

Results

Of 455 test results, a genetic variant was reported in 278 patients. Of those, 206 patients had 219 variants in COL4A3, 4, or 5 genes [112 Pathogenic/ Likely Pathogenic (P/LP), 107 Variants of Uncertain Significance (VUS)], 87 patients had 95 variants in genes associated with FSGS (22 P/LP, 73 VUS), 40 patients had 44 variants in PKHD1 (5 P/LP, 39 VUS), and 8 patients had variants in PKD2 (4 P/LP, 4 VUS).

Of the 109 patients with P/LP COL4A variants, 51 reported a previous diagnosis of Alport syndrome. Other diagnoses in patients with P/LP COL4A variants included FSGS, thin basement membrane disease, familial hematuria, hereditary nephritis, IgAN, diabetic CKD, hypertensive CKD, and ADPKD. Hearing loss was reported in 34, and eye disease was reported in 2 of the 109 patients with P/LP COL4A variants.

Conclusion

Initial results with the KIDNEYCODE panel demonstrate the utility of NGS. Combining genetic testing with clinical presentation and medical history can improve the accuracy of diagnosis of hereditary CKD.

Funding

  • Commercial Support –