Cohort profile: Canadian study of prediction of death, dialysis and interim cardiovascular events (CanPREDDICT)

Abstract

BackgroundThe Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT) is a large, prospective, pan-Canadian, cohort study designed to improve our understanding of determinants of renal and cardiovascular (CV) disease progression in patients with chronic kidney disease (CKD). The primary objective is to clarify the associations between traditional and newer biomarkers in the prediction of specific renal and CV events, and of death in patients with CKD managed by nephrologists. This information could then be used to better understand biological variation in outcomes, to develop clinical prediction models and to inform enrolment into interventional studies which may lead to novel treatments.Methods/DesignsCommenced in 2008, 2546 patients have been enrolled with eGFR between 15 and 45 ml/min 1.73m2 from a representative sample in 25 rural, urban, academic and non academic centres across Canada. Patients are to be followed for an initial 3 years at 6 monthly intervals, and subsequently annually. Traditional biomarkers include eGFR, urine albumin creatinine ratio (uACR), hemoglobin (Hgb), phosphate and albumin. Newer biomarkers of interest were selected on the basis of biological relevance to important processes, commercial availability and assay reproducibility. They include asymmetric dimethylarginine (ADMA), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), troponin I, cystatin C, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6) and transforming growth factor beta 1 (TGFβ1). Blood and urine samples are collected at baseline, and every 6 monthly, and stored at −80°C. Outcomes of interest include renal replacement therapy, CV events and death, the latter two of which are adjudicated by an independent panel.DiscussionThe baseline distribution of newer biomarkers does not appear to track to markers of kidney function and therefore may offer some discriminatory value in predicting future outcomes. The granularity of the data presented at baseline may foster additional questions.The value of the cohort as a unique resource to understand outcomes of patients under the care of nephrologists in a single payer healthcare system cannot be overstated. Systematic collection of demographic, laboratory and event data should lead to new insights.The mean age of the cohort was 68 years, 90% were Caucasian, 62% were male, and 48% had diabetes. Forty percent of the cohort had eGFR between 30–45 mL/min/1.73m2, 22% had eGFR values below 20 mL/min/1.73m2; 61% had uACR < 30. Serum albumin, hemoglobin, calcium and 25-hydroxyvitamin D (25(OH)D) levels were progressively lower in the lower eGFR strata, while parathyroid hormone (PTH) levels increased. Cystatin C, ADMA, NT-proBNP, hsCRP, troponin I and IL-6 were significantly higher in the lower GFR strata, whereas 25(OH)D and TGFβ1 values were lower at lower GFR. These distributions of each of the newer biomarkers by eGFR and uACR categories were variable.

N-Terminal Pro–B-Type Natriuretic Peptide (NT-proBNP) Immunoreactivity Is Reduced After 6 Years of Storage at −70 °C

“…The samples for this analysis (n = 99, randomly selected) were obtained from the CanPREDDICT cohort study (6) . Of these, 39% of patients had a clinically charted history of congestive heart failure (6).…”

“…Of these, 39% of patients had a clinically charted history of congestive heart failure (6). Peripheral blood samples were collected in 8.5 mL Becton Dickinson SSTs, centrifuged, decanted, and stored in aliquots in 2 mL polypropylene cryovials (Corning) at −70°C within 2 h of collection.…”

Human Heredity and Health (H3) in Africa Kidney Disease Research Network

“…The patients in the H3Africa Kidney Disease Research Network study were younger (mean6SD, 48.5614.0 years) than those in CKD cohort studies in Europe and Japan, who were a decade or more older (26)(27)(28)(29), but similar to those in CRIC (25). Of note, diabetes is less common, at 14.0%, than in the CRIC, CanPREDDICT, and CKD Japan studies, in which diabetes occurred in 29%-47% of cases (25,27,28). The H3Africa Kidney Disease Research Network study also differs from other studies in that it includes population and disease controls with no apparent kidney disease and also patients with a nephrotic syndrome.…”

“…Additional comparisons to European, Canadian, and Asian cohorts will also be important to understand the burden of CKD and the prevalence of comorbidities, such as cardiovascular disease across different ethnicities. The German CKD cohort study (26), the CKD Japan Cohort (27), the Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT) (28), and the Spanish Morbimortalidad en Enfermedad REnal en pacieNtes diAbéticos y no diabéticos (MERENA) study (29) will also allow comparison for progression. We will also have the advantage of comparison with the CKD in Children study to understand differences in children (30).…”

Predictors of a Rapid Decline of Renal Function in Patients with Chronic Kidney Disease Referred to a Nephrology Outpatient Clinic: A Longitudinal Study

“…Concurrent with this study, at least four longitudinal studies with a similar goal were published: the African American Study of Kidney Disease and Hypertension Cohort Study (AASK); the Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT); the Chronic Kidney Disease Prognosis Consortium; and the German Chronic Kidney Disease (GCKD) cohort [9][10][11][12][13][14]. These large epidemiological studies included patients with different stages of kidney failure, ages, and ethnicities, and they used classic (eGFR and albuminuria), as well as newer, biomarkers (serum fibroblast growth factor-23, vascular endothelial growth factor) [15,16] for the prediction of specific renal and cardiovascular events.…”