TY - JOUR
T1 - Diagnostic yield of massively parallel sequencing in patients with chronic kidney disease of unknown etiology
T2 - rationale and design of a national prospective cohort study
AU - de Haan, Amber
AU - Eijgelsheim, Mark
AU - Vogt, Liffert
AU - van der Zwaag, Bert
AU - van Eerde, Albertien M.
AU - Knoers, Nine V. A. M.
AU - de Borst, Martin H.
N1 - Funding Information: Funding This collaboration project is cofinanced by Sanofi Genzyme and the Dutch Ministry of Economic Affairs and Climate Policy by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships (grant numbers RVO/6320 and IMAGEN/LSHM20009). Publisher Copyright: ©
PY - 2022/4/7
Y1 - 2022/4/7
N2 - INTRODUCTION: Chronic kidney disease (CKD) can be caused by a variety of systemic or primary renal diseases. The cause of CKD remains unexplained in approximately 20% of patients. Retrospective studies indicate that massively parallel sequencing (MPS)-based gene panel testing may lead to a genetic diagnosis in 12%-56% of patients with unexplained CKD, depending on patient profile. The diagnostic yield of MPS-based testing in a routine healthcare setting is unclear. Therefore, the primary aim of the VARIETY (Validation of algoRithms and IdEnTification of genes in Young patients with unexplained CKD) study is to prospectively address the diagnostic yield of MPS-based gene panel testing in patients with unexplained CKD and an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 before the age of 50 years in clinical practice. METHODS AND ANALYSIS: The VARIETY study is an ongoing, prospective, nationwide observational cohort study to investigate the diagnostic yield of MPS-based testing in patients with unexplained CKD in a routine healthcare setting in the Netherlands. Patients are recruited from outpatient clinics in hospitals across the Netherlands. At least 282 patients will be included to meet the primary aim. Secondary analyses include subgroup analyses according to age and eGFR at first presentation, family history, and the presence of extrarenal symptoms. ETHICS AND DISSEMINATION: Ethical approval for the study has been obtained from the institutional review board of the University Medical Center Groningen. Study findings should inform physicians and policymakers towards optimal implementation of MPS-based diagnostic testing in patients with unexplained CKD.
AB - INTRODUCTION: Chronic kidney disease (CKD) can be caused by a variety of systemic or primary renal diseases. The cause of CKD remains unexplained in approximately 20% of patients. Retrospective studies indicate that massively parallel sequencing (MPS)-based gene panel testing may lead to a genetic diagnosis in 12%-56% of patients with unexplained CKD, depending on patient profile. The diagnostic yield of MPS-based testing in a routine healthcare setting is unclear. Therefore, the primary aim of the VARIETY (Validation of algoRithms and IdEnTification of genes in Young patients with unexplained CKD) study is to prospectively address the diagnostic yield of MPS-based gene panel testing in patients with unexplained CKD and an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 before the age of 50 years in clinical practice. METHODS AND ANALYSIS: The VARIETY study is an ongoing, prospective, nationwide observational cohort study to investigate the diagnostic yield of MPS-based testing in patients with unexplained CKD in a routine healthcare setting in the Netherlands. Patients are recruited from outpatient clinics in hospitals across the Netherlands. At least 282 patients will be included to meet the primary aim. Secondary analyses include subgroup analyses according to age and eGFR at first presentation, family history, and the presence of extrarenal symptoms. ETHICS AND DISSEMINATION: Ethical approval for the study has been obtained from the institutional review board of the University Medical Center Groningen. Study findings should inform physicians and policymakers towards optimal implementation of MPS-based diagnostic testing in patients with unexplained CKD.
KW - Chronic renal failure
KW - End stage renal failure
KW - GENETICS
KW - NEPHROLOGY
UR - http://www.scopus.com/inward/record.url?scp=85127831857&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/bmjopen-2021-057829
DO - https://doi.org/10.1136/bmjopen-2021-057829
M3 - Article
C2 - 35393322
SN - 2044-6055
VL - 12
SP - e057829
JO - BMJ Open
JF - BMJ Open
IS - 4
M1 - e057829
ER -