Often only CKD patients with high likelihood of genetic disease are offered genetic testing. Early genetic testing could obviate the need for kidney biopsies, allowing for adequate prognostication and treatment. To test the viability of a ‘genetics first’ approach for CKD, we performed genetic testing in a group of kidney transplant recipients <50 years, irrespective of cause of transplant.
From a cohort of 273 transplant patients, we selected 110 that were in care in the UMC Utrecht, had DNA available and were without clear-cut non-genetic disease. Forty patients had been diagnosed with a genetic disease prior to enrollment, in 70 patients we performed a whole exome sequencing based 379 gene panel analysis.
Genetic analysis yielded a diagnosis in 51%. Extrapolated to the 273 patient cohort, who did not all fit the inclusion criteria, the diagnostic yield was still 21%. Retrospectively, in 43% of biopsied patients the kidney biopsy would not have had added diagnostic value if genetic testing had been performed as a first tier diagnostic.
Burden of monogenic disease in transplant patients with ESKD of any cause prior to the age of 50 is between 21 and 51%. Early genetic testing can provide a non-invasive diagnostic, impacting prognostication and treatment and obviating the need for an invasive biopsy. We conclude that in patients who one expects to develop ESKD prior to the age of 50, genetic testing should be considered as first mode of diagnostics.

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