The relevance of genetic disease in kidney transplantation
Monica Arnaldi, Dervla M. ConnaughtonPurpose of review
Genetic disease is an increasingly recognized, but undiagnosed, cause of kidney failure. This review examines how genetics informs the evaluation and management of kidney transplant candidates and recipients.
Recent findings
Monogenic disease accounts for 10–20% of adult chronic kidney disease. In kidney transplantation cohorts, diagnostic yield increases with clinical selection, from 11% among waitlisted patients tested after excluding those with a documented genetic cause of kidney disease, to 23% in unselected kidney transplant recipients including polycystic kidney disease, to 33–54% in highly selected cohorts. Genomic testing reclassifies the cause of kidney failure in about one-third of genetically diagnosed recipients, most often correcting focal segmental glomerulosclerosis, hypertensive nephrosclerosis, or chronic kidney disease of unknown cause. Because recurrence tracks disease mechanisms rather than histology, a molecular diagnosis distinguishes nonrecurrent intrinsic kidney disease from recurrent circulating-factor and complement-mediated disease. It also identifies conditions that recur but are preventable, such as primary hyperoxaluria and adenine phosphoribosyltransferase deficiency.
Summary
Genetic testing, by targeted phenotype panels, comprehensive kidney-disease panels, or exome and genome sequencing as appropriate, should be integrated to the assessment of selected kidney transplant candidates and recipients, interpreted within a multidisciplinary team, and supported by periodic reanalysis.