# Genomic Approaches for Monogenic Kidney Diseases:
## 1 Introduction  
Chronic kidney disease (CKD) is a global public health problem with the adverse outcomes of kidney failure, cardiovascular disease and premature death. Kidney failure (KF), which is the final stage of CKD, affects approximately 9-13% of the world's population, corresponding to 800 million individuals [1; 2; 3]. In 2010, approximately 2618 million people worldwide received renal replacement therapy (RRT) [4]. This is predicated to increase to 5.4 million people by 2030 [5]. RRT impacts quality of life and life expectancy [6] and results in substantial health care costs [7].  
To address this issue, the implementation of screening and medical investigation strategies for individuals at high risk of developing KF is believed to be crucial [8]. The main reported causes of KF are diabetic nephropathy (19%) [9], glomerulonephritis (17%) and hypertensive nephropathy (16%), but in 20% of RRT cases, the etiology remains undetermined [10].  
Recent studies have shown that a genomic approach can detect the underlying cause of CKD in approximately 30% of pediatric and 5-30% of adult cases [11; 12; 13]. More than 600 monogenic genes correlated to kidney diseases [14] can be identified. Among the population with early-onset CKD (before 25 years of age), 70% of the diagnoses are congenital anomalies of the kidneys and urinary tracts, cystic diseases, glomerulonephritis and steroid-resistant nephrotic syndrome (SRNS) [15].  
A genetic diagnosis has important implications for the diagnostic and therapeutic pathways of a nephropathatic patient. More precise prognoses and therapies can be achieved whilst avoiding unnecessary and potentially harmful invasive medical investigations (e.g., renal biopsy) and futile therapies (e.g., immunosuppression). Additionally, genetic diagnosis allows genetic counseling, especially in the family planning stages.  
There are several approaches to genomic analysis, each with different diagnostic sensitivities and cost-effectiveness [16]. The most common approaches are based on three main technologies, including targeted gene panels, whole-exome sequencing (WES) and whole-genome sequencing (WGS). Sanger technology remains a validation system for next-generation sequencing (NGS) and for the analysis of small specific genes.  
However, there is a lack of consensus in the scientific community on the best diagnostic approach.  
Studies reporting the diagnostic yield of genomic diagnostic technologies vary considerably because of methodological inter-study heterogeneity. The target patients range from those with specific clinical presentations, such as SRNS, renal stones, or polycystic kidney disease, through to non-specific CKD clinical presentation and high suspicion of genetic conditions. Further, most studies are retrospective, and very few present direct comparisons of the diagnostic technologies for equivalent target populations. As a result, a conclusive evaluation of the best approach remains elusive.  
We aimed to review and evaluate the diagnostic yields of currently employed genomic testing technologies in the field of genetic kidney disease to assist professionals in selecting the best precision medicine approach.