Kidney Week 2025 Annual Meeting-Beyond Human Leukocyte Antigens: Integrating Genetics into Living Donor Kidney Transplantation

Video Transcription

Video Summary

This session focused on integrating non-HLA genetics into living donor kidney transplantation, emphasizing when genetic testing is useful, how to interpret results, and practical/ethical barriers. Dr. Christy Thomas reviewed three key areas: (1) monogenic kidney diseases (e.g., ADPKD, Alport, Fabry) where identifying a causal variant can affect donor selection and sometimes post-transplant management; (2) APOL1 high-risk genotypes as susceptibility factors for kidney disease in people of African ancestry, noting risk increases are typically modest (often ~1.7–1.9x) and modified by other variants (some additive, some neutral, some protective); and (3) pharmacogenomics, highlighting CYP3A5 genotype effects on tacrolimus metabolism—genotype-guided dosing helps reach therapeutic levels faster, though clear outcome benefits are not yet proven.<br /><br />Testing strategies were contrasted: universal screening vs targeted testing. For recipients, yields range ~10% in adults (higher in children), and targeted approaches can improve efficiency. For living donors—an asymptomatic low-risk group—universal genetic screening may generate false positives and uncertainty; a preferred approach is to first test the affected recipient, then perform targeted testing of related donors for the familial variant.<br /><br />Dr. Rashid Kabat-Egesin discussed genetic contributions to CKD and transplant outcomes, including recurrence risk in FSGS (low in monogenic forms) and emerging “minor histocompatibility antigen” loci beyond HLA (e.g., LIMS1, LILRB3) that may influence rejection and graft loss.<br /><br />Dr. Morgan Grams reviewed epidemiology and risks after donation (lower GFR, small increases in BP/preeclampsia, slightly higher ESKD risk) and how APOL1 might interact, advocating risk-based counseling tools while awaiting larger studies (e.g., APOLLO).<br /><br />Dr. Elisa Gordon addressed ethical/logistical challenges: inequities in access, limited counseling workforce, provider knowledge gaps, insurance variability, privacy/GINA limitations, and EHR integration. Proposed solutions included clinician training, better counseling infrastructure, transparent consent processes, and supportive digital tools. Discussion emphasized shared decision-making and allowing time for donors/families to process genetic information.

Asset Subtitle

Moderator(s): Yasar Caliskan, Mona Doshi

Presentation(s):

Understanding Non-HLA Genetic Factors in Kidney Transplantation - Christie Thomas
Role of Genetics in Transplant Outcomes and CKD Risk After Living Kidney Donation - Rasheed Gbadegesin
Epidemiology and Outcomes of APOL1-Mediated Kidney Disease in Living Kidney Donors - Morgan Grams
Ethical and Logistical Challenges of Genetic Testing - Elisa Gordon

Meta Tag

Date 11/8/2025

Pathway 1 Kidney Transplantation

Pathway 2 Genetic Diseases and Development

Session ID 505564

Keywords

non-HLA genetics

living donor kidney transplantation

genetic testing strategy

monogenic kidney disease

ADPKD

Alport syndrome

Fabry disease

APOL1 high-risk genotype

African ancestry kidney risk

pharmacogenomics

CYP3A5

tacrolimus dosing

FSGS recurrence risk

minor histocompatibility antigens

ethical and logistical barriers