Abstract
Advances in next-generation sequencing (NGS) techniques, including whole exome sequencing, have facilitated cost-effective sequencing of large regions of the genome, enabling the implementation of NGS in clinical practice. Chronic kidney disease (CKD) is a major contributor to global burden of disease and is associated with an increased risk of morbidity and mortality. CKD can be caused by a wide variety of primary renal disorders. In about one in five CKD patients, no primary renal disease diagnosis can be established. Moreover, recent studies indicate that the clinical diagnosis may be incorrect in a substantial number of patients. Both the absence of a diagnosis or an incorrect diagnosis can have therapeutic implications. Genetic testing might increase the diagnostic accuracy in patients with CKD, especially in patients with unknown etiology. The diagnostic utility of NGS has been shown mainly in pediatric CKD cohorts, while emerging data suggest that genetic testing can also be a valuable diagnostic tool in adults with CKD. In addition to its implications for unexplained CKD, NGS can contribute to the diagnostic process in kidney diseases with an atypical presentation, where it may lead to reclassification of the primary renal disease diagnosis. So far, only a few studies have reported on the diagnostic yield of NGS-based techniques in patients with unexplained CKD. Here, we will discuss the potential diagnostic role of gene panels and whole exome sequencing in pediatric and adult patients with unexplained and atypical CKD.
Highlights
Chronic kidney disease (CKD) affects over 850 million individuals worldwide, and is associated with an increased risk of morbidity and mortality (Go et al, 2004; Gansevoort et al, 2013; Hill et al, 2016; Jager et al, 2019) and a high burden in terms of quality of life and costs (Smith et al, 2004; Baumeister et al, 2010; Eriksson et al, 2016; Nguyen et al, 2018)
CKD is defined as decreased renal function [an estimated glomerular filtration rate lower than 60 ml/min/1.73 m2] or the presence of kidney damage, for 3 months or longer, irrespective of the underlying cause (Levey et al, 2011)
Improving Global Outcomes (KDIGO) guidelines, CKD can be classified into six stages based on estimated glomerular filtration rate (eGFR) (Table 1) and into three categories based on albuminuria (Table 2) (KDIGO, 2013)
Summary
Recent studies indicate that the clinical diagnosis may be incorrect in a substantial number of patients. Both the absence of a diagnosis or an incorrect diagnosis can have therapeutic implications. In addition to its implications for unexplained CKD, NGS can contribute to the diagnostic process in kidney diseases with an atypical presentation, where it may lead to reclassification of the primary renal disease diagnosis. Only a few studies have reported on the diagnostic yield of NGS-based techniques in patients with unexplained CKD.
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