CureGN Study Rationale, Design, and Methods: Establishing a Large Prospective Observational Study of Glomerular Disease

CureGN Consortium

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Rationale & Objectives: Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death. Study Design: Multicenter prospective cohort study. Setting & Participants: Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded. Exposures: Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year. Outcomes: Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events. Analytical Approach: The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years’ initial follow-up, CureGN has 80% power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0 mL/min/1.73 m2 in estimated glomerular filtration rate per year. Limitations: Current follow-up can only detect large differences in ESKD and death outcomes. Conclusions: Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes.

Original languageEnglish (US)
Pages (from-to)218-229
Number of pages12
JournalAmerican Journal of Kidney Diseases
Volume73
Issue number2
DOIs
StatePublished - Feb 1 2019

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Observational Studies
Prospective Studies
Chronic Kidney Failure
IGA Glomerulonephritis
Lipoid Nephrosis
Focal Segmental Glomerulosclerosis
Membranous Glomerulonephritis
Glomerular Filtration Rate
Medical History Taking
Cardiovascular Infections
Biomarkers
Kidney
Biopsy
Therapeutics
Vasculitis
Proteinuria
Immunoglobulin A
Multicenter Studies
Disease Progression
Cohort Studies

Keywords

  • adult
  • CureGN
  • digital pathology repository
  • estimated glomerular filtration rate (eGFR)
  • focal segmental glomerulosclerosis (FSGS)
  • Glomerular disease
  • glomerulonephropathy
  • Henoch-Schönlein purpura
  • IgA nephropathy (IgAN)
  • IgA vasculitis (IgAV)
  • kidney biopsy
  • longitudinal cohort
  • membranous nephropathy (MN)
  • minimal change disease (MCD)
  • patient-reported outcome (PRO)
  • pediatric
  • study design

ASJC Scopus subject areas

  • Nephrology

Cite this

CureGN Study Rationale, Design, and Methods : Establishing a Large Prospective Observational Study of Glomerular Disease. / CureGN Consortium.

In: American Journal of Kidney Diseases, Vol. 73, No. 2, 01.02.2019, p. 218-229.

Research output: Contribution to journalArticle

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abstract = "Rationale & Objectives: Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death. Study Design: Multicenter prospective cohort study. Setting & Participants: Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded. Exposures: Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year. Outcomes: Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events. Analytical Approach: The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years’ initial follow-up, CureGN has 80{\%} power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0 mL/min/1.73 m2 in estimated glomerular filtration rate per year. Limitations: Current follow-up can only detect large differences in ESKD and death outcomes. Conclusions: Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes.",
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TY - JOUR

T1 - CureGN Study Rationale, Design, and Methods

T2 - Establishing a Large Prospective Observational Study of Glomerular Disease

AU - CureGN Consortium

AU - Mariani, Laura H.

AU - Bomback, Andrew S.

AU - Canetta, Pietro A.

AU - Flessner, Michael F.

AU - Helmuth, Margaret

AU - Hladunewich, Michelle A.

AU - Hogan, Jonathan J.

AU - Kiryluk, Krzysztof

AU - Nachman, Patrick H.

AU - Nast, Cynthia C.

AU - Rheault, Michelle N.

AU - Rizk, Dana V.

AU - Trachtman, Howard

AU - Wenderfer, Scott E.

AU - Bowers, Corinna

AU - Hill-Callahan, Peg

AU - Marasa, Maddalena

AU - Poulton, Caroline J.

AU - Revell, Adelaide

AU - Vento, Suzanne

AU - Barisoni, Laura

AU - Cattran, Dan

AU - D'Agati, Vivette

AU - Jennette, J. Charles

AU - Klein, Jon B.

AU - Laurin, Louis Philippe

AU - Twombley, Katherine

AU - Falk, Ronald J.

AU - Gharavi, Ali G.

AU - Gillespie, Brenda W.

AU - Gipson, Debbie S.

AU - Greenbaum, Larry A.

AU - Holzman, Lawrence B.

AU - Kretzler, Matthias

AU - Robinson, Bruce

AU - Smoyer, William E.

AU - Guay-Woodford, Lisa M.

AU - Ahn, Wooin

AU - Appel, Gerald B.

AU - Babayev, Revekka

AU - Batal, Ibrahim

AU - Brown, Eric

AU - Campenot, Eric S.

AU - Canetta, Pietro

AU - Carlassara, Lucrezia

AU - Chan, Brenda

AU - Chatterjee, Debanjana

AU - D'Agati, Vivette D.

AU - Delbarba, Elisa

AU - Sambandam, Kamalanathan K

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Rationale & Objectives: Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death. Study Design: Multicenter prospective cohort study. Setting & Participants: Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded. Exposures: Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year. Outcomes: Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events. Analytical Approach: The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years’ initial follow-up, CureGN has 80% power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0 mL/min/1.73 m2 in estimated glomerular filtration rate per year. Limitations: Current follow-up can only detect large differences in ESKD and death outcomes. Conclusions: Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes.

AB - Rationale & Objectives: Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death. Study Design: Multicenter prospective cohort study. Setting & Participants: Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded. Exposures: Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year. Outcomes: Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events. Analytical Approach: The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years’ initial follow-up, CureGN has 80% power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0 mL/min/1.73 m2 in estimated glomerular filtration rate per year. Limitations: Current follow-up can only detect large differences in ESKD and death outcomes. Conclusions: Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes.

KW - adult

KW - CureGN

KW - digital pathology repository

KW - estimated glomerular filtration rate (eGFR)

KW - focal segmental glomerulosclerosis (FSGS)

KW - Glomerular disease

KW - glomerulonephropathy

KW - Henoch-Schönlein purpura

KW - IgA nephropathy (IgAN)

KW - IgA vasculitis (IgAV)

KW - kidney biopsy

KW - longitudinal cohort

KW - membranous nephropathy (MN)

KW - minimal change disease (MCD)

KW - patient-reported outcome (PRO)

KW - pediatric

KW - study design

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DO - 10.1053/j.ajkd.2018.07.020

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EP - 229

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

SN - 0272-6386

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