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Kidney Week

Abstract: PO1290

Early Experience with Broad-Panel Genetic Testing in Pre- and Post-Transplant Evaluation of Patients with Kidney Failure

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Sodhi, Rupi K., Loyola University Medical Center, Maywood, Illinois, United States
  • Desai, Amishi S., Loyola University Medical Center, Maywood, Illinois, United States
  • Yoo, Jongwon, Loyola University Medical Center, Maywood, Illinois, United States
  • Arwindekar, Divya Jain, Loyola University Medical Center, Maywood, Illinois, United States
  • Brossart, Katya, Natera, Inc., San Carlos, California, United States
  • Tabriziani, Hossein, Natera, Inc., San Carlos, California, United States
  • Akkina, Sanjeev, Loyola University Medical Center, Maywood, Illinois, United States
Background

Genetic testing plays an important role in kidney transplantation (KT). Genetic assessment during the pre-KT workup enables more accurate estimation of the risk of recurrent kidney disease and informs treatment of recurrence living-related kidney donor selection. Testing with a broad genetic panel may be beneficial for patients with advanced disease. Here we describe an academic transplant center’s early experience with a >380-gene kidney disease panel using NGS, with variant confirmation via orthogonal methods.

Methods

Twenty-six pre- and post-KT patients underwent genetic testing between June 2020 and April 2021. Patients ranged in age from 28 to 67 years, with a median age of 31 years. Genetic testing results were correlated to clinical histories, including biopsy (when available), ultrasound results, presence of proteinuria and hematuria, demographic factors, family history and comorbidities. Certified genetic counselors interpreted the results and provided consultation to patients on request.

Results

Positive findings were identified in 38.5% (10/26) of patients tested, in TTR, COL4A3, COL4A4, COL4A5, COL11A1, INF2, and PKD1. Two patients with a pathogenic variant in the TTR gene also had 2 APOL1 risk alleles (G1 and/or G2). Genetic findings confirmed clinical disease in 1 individual, identified a subcategory of clinical disease in 2 individuals, reclassified disease in 3 individuals, and established a molecular diagnosis in 4 individuals. In this cohort, 8 individuals received a KT, of which 6 had no pathogenic variant identified. Of those 6, two had biopsy proven glomerular disease that recurred after early KT, implicating a non-inherited cause of renal disease. Identification of positive pathogenic variants in 75% (3/4) of patients evaluated for a living related donor transplantation, prompted evaluation of the intended donors.

Conclusion

Identification of patients awaiting KT who are at increased risk of a monogenic disease can result in a high yield via a broad-panel testing approach. The implications of a genetic diagnosis in this cohort are multifaceted, with potential to impact care and identify family members who may be at risk for kidney failure, and to enable early diagnosis and intervention.