Kidney Week 2025 Early Program - Genetics in Clinical Nephrology-Multidisciplinary Workshop #2 - Genetic Risk, Familial Segregation, and Ethical Considerations in Living Kidney Donation

Video Transcription

Video Summary

This workshop uses a transplant case to explore genetic kidney disease and ethical decision-making in living donation. A 31-year-old Colombian man with biopsy-labeled FSGS progressed to kidney failure and is evaluated for transplant; his 56-year-old mother volunteers as donor but has isolated microscopic hematuria and a past kidney stone. The audience debates whether to biopsy and/or perform genetic testing, generally favoring testing the son first with a broad kidney gene panel. Testing reveals a likely pathogenic hemizygous COL4A5 variant (X-linked Alport syndrome) plus APOL1 risk alleles. The mother’s biopsy shows thin basement membrane changes, consistent with heterozygous COL4A5 status.<br /><br />The panel discusses whether she should be accepted as a donor, emphasizing uncertain but meaningful lifetime kidney failure risk in heterozygous females, strong age effects (higher concern under 40, pregnancy risks), and limited, biased outcome data on Alport carriers who donate. APOL1 is reviewed: two risk alleles raise kidney disease and post-donation risk; emerging African data suggest heterozygotes may also have increased risk, though relevance to Colombians is unclear. A powerful letter from the mother illustrates psychosocial motivations and shifts opinions toward allowing donation.<br /><br />Ethical questions include whether donor-recipient relationship should matter, whether genetic testing should be optional or effectively required for informed consent, and how to decide when multiple relatives may need transplants. The session covers cascade testing in an X-linked pedigree and debates pediatric testing, weighing early treatment benefits (especially for boys with X-linked Alport) against a child’s “right to an open future,” psychosocial harms, and potential insurance discrimination (notably for APOL1). The real outcome: the mother donated 11 years earlier; later developed hypertension and mild proteinuria; the son’s Alport diagnosis came years after transplant and he ultimately returned to dialysis.

Asset Subtitle

Alice Doreille, Daniel P. Gale, Maya Sabatello

Meta Tag

Module GENE

Speaker FACULTY FACULTY

Keywords

living kidney donation ethics

genetic kidney disease

X-linked Alport syndrome

COL4A5 variant

FSGS misdiagnosis

thin basement membrane nephropathy

APOL1 risk alleles

kidney transplant donor evaluation

cascade genetic testing

pediatric genetic testing ethics