Association of Clonal Hematopoiesis of Indeterminate Potential with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney Disease.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is an inflammatory premalignant disorder resulting from acquired genetic mutations in hematopoietic stem cells. This condition is common in aging populations and associated with cardiovascular morbidity and overall mortality, but its role in CKD is unknown.

Methods: We performed targeted sequencing to detect CHIP mutations in two independent cohorts of 87 and 85 adults with an eGFR<60 ml/min per 1.

Defining the Scope of Knowledge Translation Within a National, Patient-Oriented Kidney Research Network.

Purpose Of Program: Integrated knowledge translation (IKT) is a collaborative approach whereby knowledge created through health research is utilized in ways that are relevant to the needs of all stakeholders. However, research teams have limited capacity and know-how for achieving IKT, resulting in a disconnect between the generation and application of knowledge. The goal of this report is to describe how IKT research was achieved across a large-scale, patient-oriented research network, Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD).

A Framework to Ensure Patient Partners Have Equal and Contributing Voices Throughout the Research Program Evaluation Process.

Purpose Of Program: Traditionally, peer review was a closed process conducted only by individuals working in the research field. To establish a more integrated and patient-centered approach, one of Canada's largest kidney research networks (Can-SOLVE CKD) has created a Research Operations Committee (ROC) that includes patients as key members. The ROC represents one way for achieving meaningful patient-oriented research (POR).

Conversion of Urine Protein-Creatinine Ratio or Urine Dipstick Protein to Urine Albumin-Creatinine Ratio for Use in Chronic Kidney Disease Screening and Prognosis : An Individual Participant-Based Meta-analysis.

Background: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead.

Objective: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging.

Design: Individual participant-based meta-analysis.

Glomerular Filtration Rate-Specific Cutoffs Can Refine the Prognostic Value of Circulating Cardiac Biomarkers in Advanced Chronic Kidney Disease.

Background: Using standard cutoffs derived from healthy adults, high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are frequently elevated in patients with reduced glomerular filtration rate (GFR), with unclear implications. We sought to compare GFR-specific cutoffs of each biomarker with standard cutoffs for discrimination of cardiovascular risk in asymptomatic patients with chronic kidney disease.

Methods: We investigated a prospective cohort of 1956 participants with median GFR of 27 mL/min/1.

GFR-Specific versus GFR-Agnostic Cutoffs for Parathyroid Hormone and Fibroblast Growth Factor-23 in Advanced Chronic Kidney Disease.

Background: In the majority of patients with advanced chronic kidney disease (CKD), values of parathyroid hormone (PTH1-84) and fibroblast growth factor 23 (FGF-23) exceed the normal reference range, potentially as an appropriate adaptation to reduced glomerular filtration rate (GFR). We tested whether GFR-specific cutoffs for PTH1-84 and FGF-23 could better identify patients with inappropriately high PTH1-84 and FGF-23 for their degree of CKD and thereby improve prognostication of clinical outcomes compared to a uniform threshold.

Methods: Prospective pan-Canadian cohort of 1,812 patients with mean estimated GFR (eGFR) 28.

The Risk of Adverse Events in Patients With Polycystic Kidney Disease With Advanced Chronic Kidney Disease.

Background: Polycystic kidney disease (PKD) leads to progressive chronic kidney disease (CKD) with a subsequent risk of adverse events such as cardiac disease, infections, end-stage kidney disease (ESKD), and mortality.

Objectives: To determine the risks of CKD-related adverse outcomes in patients with PKD compared with patients without PKD.

Setting: Canadian study of prediction of death, dialysis and interim cardiovascular events (CanPREDDICT) was a prospective pan-Canadian cohort study from 2008-2013 involving 28 facilities with adjudicated outcomes.

Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD): Form and Function.

Purpose Of Review: This article serves to describe the Can-SOLVE CKD network, a program of research projects and infrastructure that has excited patients and given them hope that we can truly transform the care they receive.

Issue: Chronic kidney disease (CKD) is a complex disorder that affects more than 4 million Canadians and costs the Canadian health care system more than $40 billion per year. The evidence base for guiding care in CKD is small, and even in areas where evidence exists, uptake of evidence into clinical practice has been slow.

The Variability of Estimated Glomerular Filtration Rate Decline in Alport Syndrome.

Background: A progressive trajectory toward renal failure is common in patients with Alport syndrome. Genotype-phenotype correlations have been well described; however, the natural history of the trajectory toward renal failure is not well described.

Objective: The objective of this study is to describe the natural history of renal function decline in a cohort of Alport syndrome patients.

Randomized Controlled Trial for the Effect of Vitamin D Supplementation on Vascular Stiffness in CKD.

Background And Objectives: Vitamin D is implicated in vascular health in CKD. This study compared placebo, calcifediol, and calcitriol treatment with changes in vascular stiffness, BP, proteinuria, mineral metabolism parameters, C-reactive protein, and fibroblast growth factor 23 in patients with stable CKD.

Design, Setting, Participants, & Measurements: We conducted a double-blind, randomized controlled trial in out-patient CKD clinics in Vancouver, Canada, from February of 2011 to August of 2014, enrolling 119 patients with an eGFR of 15-45 ml/min per 1.

Cardiovascular risk is similar in patients with glomerulonephritis compared to other types of chronic kidney disease: a matched cohort study.

Background: Patients with chronic kidney disease (CKD) due to glomerulonephritis (GN) are thought to be at high risk for cardiovascular disease (CVD). However, no study has examined whether GN directly contributes to CV risk beyond the effects conferred by pre-existing traditional risk factors and level of renal function.

Methods: Matched cohort study using the previously described prospective CanPREDDICT study cohort.

The Association between Biomarker Profiles, Etiology of Chronic Kidney Disease, and Mortality.

Background: Prognosis in chronic kidney disease (CKD) for adverse outcomes differs substantially based on the etiology of CKD. We examined whether the biomarker profile differed based on CKD etiology and whether they were associated with mortality.

Methods: Prospective observational study of 1,157 patients, 663 with diabetic kidney disease (DKD), 273 with glomerulonephritis (GN), and 221 with cystic/interstitial disease (polycystic kidney disease, pyelonephritis or chronic tubulointerstitial nephritis [PCK/TIN]) were identified in the Canadian Study of Prediction of Dialysis, Death and Interim Cardiovascular events over Time cohort.

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

Background: Clinical trial samples may be stored frozen for prolonged periods before analysis, which can reduce the immunoreactivity of numerous analytes, particularly peptides. We sought to determine the effect of 6 years of frozen storage on serum N-terminal pro-B-type natriuretic peptide (NT-proBNP).

Methods: NT-proBNP was measured from serum samples taken from 99 different patients enrolled in the CanPREDDICT study after <1 year of storage at -70 °C using the Roche first-generation NT-proBNP assay on an e411 instrument.

Infection in advanced chronic kidney disease leads to increased risk of cardiovascular events, end-stage kidney disease and mortality.

The risk of infection in advanced chronic kidney disease (CKD) and its subsequent impact on adverse outcomes are not well established. Therefore, we determined the association of an infectious episode with the subsequent risk of cardiovascular ischemia, congestive heart failure, end-stage kidney disease or mortality in a Canadian prospective cohort (CanPREDDICT) of patients with advanced CKD (eGFR: 15-45 ml/min/1.73m(2)) followed by nephrologists for up to 5 years.

Advanced chronic kidney disease populations have elevated trimethylamine N-oxide levels associated with increased cardiovascular events.

Cardiovascular disease is more common in patients with chronic kidney disease (CKD), and traditional risk factors do not adequately predict those at risk for cardiovascular (CV) events. Recent evidence suggests elevated trimethylamine N-oxide (TMAO), created by gut microflora from dietary L-carnitine and choline, is associated with CV events. We investigated the relationship of TMAO levels in patients with stages 3b and 4 CKD to ischemic CV events using the CanPREDDICT cohort, a Canada-wide observational study with prospective 3-year follow-up of adjudicated CV events.

A randomized control trial to assess the impact of vitamin D supplementation compared to placebo on vascular stiffness in chronic kidney disease patients.

Background: Vitamin D deficiency is associated with cardiovascular (CV) risk in multiple populations, including those with chronic kidney disease (CKD). The active form of the hormone (1,25 OH2D3) binds to receptors in multiple organs. CKD patients are deficient in both 25 Vitamin D and 1,25 OH2D3.

Biomarkers of inflammation, fibrosis, cardiac stretch and injury predict death but not renal replacement therapy at 1 year in a Canadian chronic kidney disease cohort.

Background: Newer biomarkers, reflective of biological processes, such as inflammation and fibrosis, cardiac stretch or damage and vascular health may be useful in understanding clinical events in chronic kidney disease (CKD). We assessed whether these newer biomarkers, alone or as a panel, improve risk prediction for renal replacement therapy or death, over and above conventional clinical, demographic and laboratory variables.

Methods: We conducted a prospective observational Canadian cohort study in 2544 CKD patients with estimated glomerular filtration rate (eGFR) of 15-45 mL/min/1.

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

Background: The 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.

Responsiveness of FGF-23 and mineral metabolism to altered dietary phosphate intake in chronic kidney disease (CKD): results of a randomized trial.

Background: High fibroblast growth factor-23 (FGF-23) levels are associated with adverse outcomes. We studied the responsiveness of FGF-23 and mineral metabolism to altered dietary phosphate intake in chronic kidney disease (CKD) and healthy control patients.

Methods: Thirty patients were enrolled: 18 normophosphatemic CKD subjects and 12 healthy controls.

Vascular stiffness in incident peritoneal dialysis patients over time.

Objective: Vascular stiffness is prevalent in end-stage renal disease patients and predicts adverse events. This study describes the prevalence of vascular stiffness and its associated factors in a cohort of incident peritoneal dialysis (PD) patients.

Methods: In a prospective observational study of 50 patients, carotid-femoral pulse wave velocity (PWV) were conducted at baseline, 3, 6 and 12 months after initiation of PD.

Genetic variations of NAT2 and CYP2E1 and isoniazid hepatotoxicity in a diverse population.

Aims: TB is a serious global public health problem. Isoniazid, a key drug used to treat latent TB, can cause hepatotoxicity in some patients. This pilot study investigated the effects of genetic variation in NAT2 and CYP2E1 on isoniazid-induced hepatotoxicity in TB contacts in British Columbia, Canada.