Genetic testing in adult-onset chronic kidney disease: unravelling a VARIETY of specific monogenic causes

The cause of chronic kidney disease (CKD) remains unknown in at least 20% of patients. In this thesis, we assessed the diagnostic value of genetic testing in adult patients with unexplained CKD in a clinical setting. We found a genetic diagnosis in 17% of adult patients with unexplained CKD. Genetic testing not only allowed for a diagnosis in 17% of patients, but it also led to clinical consequences in 73%, ranging from transplantation implications to changes in therapy. These results show the relevance of genetic testing in the diagnostic workup of adults with unexplained CKD. Furthermore, we found that a positive family history of CKD is an independent predictor for receiving a genetic diagnosis. However, even among patients with a negative family history, a genetic diagnosis can still be identified in 13% of patients, indicating that genetic testing should be offered to both patients with and without a family history of CKD. Age at onset CKD was not a predictor of diagnostic yield. Moreover, in this thesis, we describe two families in which genetic testing identified the cause of kidney failure. Additionally, we show that Dutch nephrologists encounter several barriers in implanting genetic testing into daily practice. Many of these barriers can be overcome by more genetic education. The results from this thesis show that genetic testing is a useful diagnostic tool in the clinical workup of adults with unexplained CKD. It additionally shows that genetic educational programs for nephrologists may enhance the use of genetic testing in daily practice.