Genetic testing: Key to diagnosis in patients with unexplained chronic kidney disease
The main goal of this public-private collaboration between the University Medical Center Groningen and Sanofi Genzyme is to investigate the diagnostic yield of genetic testing (next-generation sequencing, NGS) in patients with unexplained chronic kidney disease (CKD).
In about one in five patients with end-stage renal disease, the cause for the kidney disease cannot be established, and in many others the diagnosis is inaccurate. The absence of a diagnosis or an incorrect diagnosis can have therapeutic implications.
Recent studies have shown that in research setting a molecular diagnosis can be established with NGS in 12%-56% of patients with unexplained CKD. However, these findings require prospective validation in a routine healthcare setting.
The purpose of this study therefore is to establish a national cohort of patients with unexplained CKD in the Netherlands. In this cohort the diagnostic yield of a NGS multi-gene panel for renal diseases will be determined. This observational study will use available patient data to establish the VARIETY cohort. Patients will be recruited from academic and non-academic hospitals across the Netherlands. The main inclusion criterion is unexplained (i.e. unknown cause or atypical presentation) CKD stage with an estimated glomerular filtration rate <60 ml/minute/1.73m2 before the 50 years of age. The data will be collected, stored, and analysed at the UMCG. They strive to include 400 patients in 4 years.
The primary outcome is the number of patients with a molecular diagnosis (i.e. the identification of a gene mutation known to cause CKD) using the NGS-based multi-gene panel approach. The results of this study may influence the diagnostic workup of patients with unexplained CKD in clinical practice, and may inform policymakers how to optimally implement genetic testing.
