The Canadian Glomerulonephritis Registry and Translational Research Initiative (CGNR)

The SPOR Canadian Glomerulonephritis Registry and Translational Research Initiative

Glomerulonephritis (GN) is one of the most important causes of kidney failure in Canada. These comprise a group of "rare" diseases (<5 per 250,000 population), yet GN is a leading cause of kidney failure and accounts annually for close to 20% of incident cases of end stage kidney disease (ESKD) in Canada. Prevention of progression to kidney failure is possible, however several barriers and gaps in knowledge challenge our ability to provide patients with individualized effective therapy. These include a lack of sensitive non-invasive tools for monitoring disease activity, prognosis, and response to therapy. A gap in understanding of the core molecular processes underlying the development and progression of GN, and a lack of cohesive networks for evaluation of novel treatment approaches contribute to a lack of targeted and personalized therapies for GN. To address these challenges we will create a national, multi-dimensional platform for application of human-based molecular research and advanced therapeutics in GN.

Study Overview

• Status: Recruiting
• Conditions: Glomerular Nephritis

Detailed Description

To accomplish the goals set out in this project, the CGNR network will recruit and maintain a large cohort of patients 350 with glomerular diseases and follow them prospectively with standardized clinical data and biospecimen collection. The infrastructure and study design presented in this protocol will form the backbone for a broad range of scientific approaches and inquiries, essential to moving the field forward and improving the outcomes of patients affected by these diseases. Successful recruitment of 350 patients from across the country, creating a rich biobank and data repository. Our aims are to identifying patient characteristics associated with glomerular diseases and complications, characterizing disease trajectory under current clinical care, estimating event rates of clinically meaningful outcomes, identify predictors of short and long-term outcomes including therapeutic outcomes. We also aim to identify and characterize clinical, histological, molecular and genetic biomarkers that are linked to glomerular diseases and outcomes that might improve disease classification, and biomarkers that may be employed in clinical practice or in clinical trials that predict disease activity or response to therapy. Furthermore, we propose to study sequence variations, transcriptome profile and their impact on disease presentation and clinical outcome. On the patient level, we will identify patient reported outcomes such as disease burden, physical function and quality of life associated with GN diseases and validate tools to assess impact of disease and therapy on patients. Achievement of our goals will be determined by the success of the research studies that evolve from the biobank, and data repository.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

• Study Contact: Name: Heather Reich, MD; Phone Number: 416-340-3439; Email: heather.reich@uhn.ca
• Study Contact Backup: Name: Ping Lam, PhD; Phone Number: 416-340-3514; Email: ping.lam@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2C4
      • Recruiting
      • University Health Network
      • Contact: Ping Lam, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

- Adult patient who has biopsy proven IgAN or FSGS, MCD, MGN, MPGN with kidney function GFR>=30

Description

Inclusion Criteria:

• diagnosis of IgAN, FSGS, MCD, MGN, MPGN
• age 18-80 inclusive
• estimated GFR>=30ml/min/1.73m2 estimated using 4 variable MDRD
• first kidney biopsy within 12 months of enrollment
• connective tissue disease serology is normal/negative ANA, ANCA

Exclusion Criteria:

• Systemic lupus erythematosus (SLE) - serology supported
• Evidence of diabetic nephropathy on renal biopsy
• Underlying connective tissue disease and/or serologic evidence (sarcoid, rheumatoid arthritis, vasculitis)
• Prior organ transplant

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
IgA Nephropathy (IgAN); Biopsy-Proven IgAN
Focal Segmental Glomerulosclerosis (FSGS); Biopsy-Proven FSGS
Membranous Nephropathy (MGN); Biopsy-Proven MGN
Mesangioproliferative Glomerulonephritis (MPGN); Biopsy-Proven MPGN
Minimal Change Disease (MCD); Biopsy-Proven MCD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite renal outcome (Estimated Glomerular Filtration Rate)	End Stage Renal Disease (eGFR<15 or dialysis>60 days) or 40% decline in GFR at 2 years	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of renal function decline	slope of least-squares regression line calculated for each person over 2 years	2 years
Complete remission of proteinuria	proteinuria <0.3g/day	2 years
Partial remission of proteinuria	Defined by % reduction in 24 hour protein excretion from peak value	2 years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Sunnybrook Health Sciences Centre; CHU de Quebec-Universite Laval; University of Alberta; McGill University Health Centre/Research Institute of the McGill University Health Centre; The Ottawa Hospital; Providence Health & Services; Queen Elizabeth II Health Sciences Centre; Foothills Medical Centre
• Investigators: Principal Investigator: Heather Reich, MD, Nephrologist

Publications and helpful links

General Publications

• Hildebrand AM, Barua M, Barbour SJ, Tennankore KK, Cattran DC, Takano T, Lam P, De Serres SA, Samanta R, Hladunewich MA, Fairhead T, Poyah P, Bush DD, MacLaren B, Sparkes D, Boll P, Jauhal A, John R, Avila-Casado C, Reich HN. The Canadian Glomerulonephritis Registry (CGNR) and Translational Research Initiative: Rationale and Clinical Research Protocol. Can J Kidney Health Dis. 2022 Apr 8;9:20543581221089094. doi: 10.1177/20543581221089094. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2017
• Primary Completion (Anticipated): December 30, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: February 16, 2018
• First Submitted That Met QC Criteria: March 2, 2018
• First Posted (Actual): March 9, 2018

Study Record Updates

• Last Update Posted (Actual): March 9, 2018
• Last Update Submitted That Met QC Criteria: March 2, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Glomerulonephritis; Nephritis
• Other Study ID Numbers: CAPCR 16-6110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No