A multidisciplinary approach to genetic testing in the kidney transplant evaluation clinic provides useful input for selection of kidney donors and management of transplant recipients, suggests an evaluation in Transplantation.
The authors describe their experience in implementing a multidisciplinary genetic testing approach for potential kidney donors and recipients at the transplant clinic of a major medical center. Between 2018 and 2020, recipients were considered for genomic evaluation, based on previously published criteria. Genetic testing was also considered for potential donors to biologically related recipients with genetic causes of kidney diseases.
Genomic DNA testing was performed using a custom-curated exome slice gene panel, comprising 344 genes linked to various kidney diseases and candidate genes highly expressed in the kidney. Each patient considered for genetic testing was reviewed by a nephrology genomic board consisting of nephrologists with expertise in genetic causes of kidney diseases, renal pathologists, researchers, medical geneticists, and genetic counselors with expertise in kidney diseases.
Of 1100 transplant evaluations performed between 2018 and 2020, 34 recipients were selected for genetic testing. Approximately three-fourths of patients were non-Hispanic White individuals. Testing was canceled in four patients, mainly due to reimbursement issues.
Testing led to genetic diagnosis of a pathogenic or likely pathogenic variant in 13 of 30 patients—a rate of 43.4%. Of 24 tested patients with focal segmental glomerulosclerosis (FSGS), 10 (41.6%) had a genetic diagnosis. Collagen type 4 gene variants were detected in 7 of the 24 patients with FSGS.
Other genetic diagnoses included tubulointerstitial nephritis, nephrolithiasis, and unknown causes of kidney diseases. The only clinical characteristic associated with positive versus negative results was family history of kidney diseases: 76.9% versus 29.4%, respectively. Testing of five potential donors led to exclusion of one individual with a pathogenic or likely pathogenic variant.
With a careful selection approach, diagnosis of a pathogenic or likely pathogenic variant is made in approximately 40% of patients selected for genetic testing at a transplantation clinic. This approach “facilitated the screening of potential living related donors and counseling of recipients about risk of recurrence of their native disease, which are of particular importance in FSGS,” the researchers write. They emphasize the importance of a multidisciplinary approach, focused on achieving transplant-specific goals while providing patients with genetic counseling both before and after testing [El Ters M, et al. Incorporation of genetic studies in the kidney transplant evaluation clinic: The value of a multidisciplinary approach. Transplantation 2023; 107:952–960; doi: 10.1097/TP.0000000000004363].