Genetic testing in kidney transplantation and living kidney donor risk assessment.
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Schott Clara, Relouw Sydney, Arnaldi Monica, Baker Cadence, Offerni-Almada Gabriela, Wang Jian, McIntyre Adam D, Son Surim, Cuerden Meaghan, Arnold Jennifer B, Burman Nikita, Colaiacovo Samantha, Solo Karla, Boudville Neil, Dipchand Christine, Feldman Liane S, Gill John, Gunaratnam Lakshman, House Andrew A, Iyer Hariharan, Johnson John, Karpinski Martin, Klarenbach Scott, Knoll Greg, Lok Charmaine E, Lotfy Khaled, Miller Matthew, Monroy-Cuadros Mauricio, Nguan Christopher, Rehman Faisal, Roshanov Pavel S, Prasad G V Ramesh, Storsley Leroy, Weir Matthew A, Hegele Robert A, Garg Amit X, Connaughton Dervla M
Аннотация
METHODS: Genetic testing was performed in 231 transplant recipients and 46 prospective LKDs by means of exome sequencing of 409 chronic kidney disease (CKD)-associated genes. We also assessed 122 retrospective LKDs who developed adverse kidney outcomes post-donation which were defined by at least two of the three criteria: hypertension, a glomerular filtration rate under 60 mL/min/1.73m2, or a urine albumin to creatinine ratio of 3 mg/mmol or more.
RESULTS: Pathogenic or likely pathogenic (P/LP) variants were identified in 23% of recipients, most commonly involving genes associated with cystic kidney disease and glomerulopathies. Among the recipients with a genetic diagnosis, there was a 37% rate of reclassification to a different phenotype post genetic testing. Among prospective LKDs, 4% had P/LP variants. In the retrospective cohort of LKDs with adverse kidney outcomes post donation, 19% carried P/LP variants.
CONCLUSIONS: Genetic testing yielded a high diagnostic rate and frequently reclassified CKD etiology in transplant recipients, underscoring its diagnostic utility. Universal genetic testing of asymptomatic LKDs had a yield of 4%, although our prospective LKD cohort had limited sample size. In contrast, high proportion of LKDs with adverse kidney outcome post-donation were found to carry P/LP variants in CKD-associated genes. Our findings suggest that targeted genetic testing of high-risk donors may be a preferred over universal testing strategy to optimize donor selection in LKDs. However, further evaluation is warranted to ensure this approach appropriately balances donor safety with equitable access.