Kidney Failure Risk Equation in vascular access planning: a population-based study supporting value in decision making.

Background: The Kidney Failure Risk Equation (KFRE) can play a better role in vascular access (VA) planning in patients with chronic kidney disease (CKD) requiring hemodialysis (HD). We described the VA creation and utilization pattern under existing estimated glomerular filtration rate (eGFR)-based referral, and investigated the utility of KFRE score as an adjunct variable in VA planning. Methods: Patients with CKD aged ≥18 years with eGFR <20 mL/min/1.73 m2 who chose HD as dialysis modality from January 2010 to August 2020 were included from a population-based database in British Columbia, Canada. Modality selection date was the index date. Exposures were categorized as (i) current eGFR-based referral, (ii) eGFR-based referral plus KRFE 2-year risk score on index date (KFRE-2) >40% and (iii) eGFR-based referral plus KFRE-2 ≤40%. We estimated the proportion of patients who started HD on arteriovenous fistula/graft (AVF/G) within 2 years, indicating timely pre-emptive creation, and the proportion of patients in whom AVF/G was created but did not start HD within 2 years, indicating too-early creation. Results: Study included 2581 patients, median age 71 years, 60% male. Overall, 1562(61%) started HD and 276 (11%) experienced death before HD initiation within 2 years. Compared with current referral, the proportion of patients who started HD on AVF/G was significantly higher when KFRE-2 was considered in addition to current referral (49% vs 58%, P-value <.001). Adjunct KFRE-2 significantly reduced too-early creation (31% vs 18%, P-value <.001). Conclusions: KFRE in addition to existing eGFR-based referral for VA creation has the potential to improve VA resource utilization by ensuring more patients start HD on AVF/G and may minimize too-early/unnecessary creation. Prospective research is necessary to validate these findings.

Safety and Effectiveness of Rivaroxaban Versus Warfarin Across GFR Levels in Atrial Fibrillation: A Population-Based Study in Australia and Canada.

Rationale & Objective: The benefit-risk profile of rivaroxaban versus warfarin for atrial fibrillation (AF) in patients with chronic kidney disease is uncertain. We compared rivaroxaban with warfarin across the range of kidney function in adults with AF. Study Design: Multicenter retrospective cohort. Setting & Participants: Adults with AF and a measure of estimated glomerular filtration rate (eGFR); using administrative data from 5 jurisdictions across Australia and Canada (2011-2018). Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. Patients receiving dialysis and kidney transplant recipients were excluded. Exposures: New dispensation of either rivaroxaban or warfarin. Outcomes: Composite (1) effectiveness outcome (all-cause death, ischemic stroke, or transient ischemic attack) and (2) major bleeding events (intracranial, gastrointestinal, or other) at 1 year. Analytical Approach: Cox proportional hazards models accounting for propensity score matching were performed independently in each jurisdiction and then pooled using random-effects meta-analysis. Results: 55,568 patients (27,784 rivaroxaban-warfarin user matched pairs; mean age 74 years, 46% female, 33.5% with eGFR <60 mL/min/1.73 m2) experienced a total of 4,733 (8.5%) effectiveness and 1,144 (2.0%) bleeding events. Compared to warfarin, rivaroxaban was associated with greater or similar effectiveness across a broad range of kidney function (pooled HRs of 0.72 [95% CI, 0.66-0.78], 0.78 [95% CI, 0.58-1.06], 0.70 [95% CI, 0.57-0.87], and 0.78 [95% CI, 0.62-0.99]) for eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively). Rivaroxaban was also associated with similar risk of major bleeding across all eGFR categories (pooled HRs of 0.75 [95% CI, 0.56-1.00], 1.01 [95% CI, 0.79-1.30], 0.87 [95% CI, 0.66-1.15], and 0.63 [95% CI, 0.37-1.09], respectively). Limitations: Unmeasured treatment selection bias and residual confounding. Conclusions: In adults with AF, rivaroxaban compared with warfarin was associated with lower or similar risk of all-cause death, ischemic stroke and transient ischemic attack and similar risk of bleeding across a broad range of kidney function. Plain-Language Summary: This real-world study involved a large cohort of 55,568 adults with atrial fibrillation from 5 jurisdictions across Australia and Canada. It showed that the favorable safety (bleeding) and effectiveness (stroke or death) profile of rivaroxaban compared with warfarin was consistent across different levels of kidney function. This study adds important safety data on the use of rivaroxaban in patients with reduced kidney function, including those with estimated glomerular filtration rate <30 mL/min/1.73 m2 in whom the risks and benefits of rivaroxaban use is most uncertain. Overall, the study supports the use of rivaroxaban as a safe and effective alternative to warfarin for atrial fibrillation across differing levels of kidney function.

Long-term effect of COVID-19 infection on kidney function among COVID-19 patients followed in post-COVID-19 recovery clinics in British Columbia, Canada.

BACKGROUND: We investigated the effect of Post-Acute COVID Syndrome or "long-COVID" on kidney function among patients followed in post-COVID recovery clinics (PCRC) in British Columbia, Canada. METHODS: Long-COVID patients referred to PCRC between July 2020 to April 2022, aged ≥18 years who had an estimated glomerular filtration rate (eGFR) value recorded at 3 months from the coronavirus disease 2019 (COVID-19) diagnosis (index) date were included. Those requiring renal replacement therapy prior to index date were excluded. Primary outcome was change in eGFR and urine albumin-creatinine ratio (UACR) after COVID-19 infection. The proportion of patients in each of the six eGFR categories (<30, 30-44, 45-59, 60-89, 90-120 and >120 mL/min/1.73 m2) and three UACR categories (<3, 3-30 and >30 mg/mmol) in all of the study time points were calculated. Linear mixed model was used to investigate change in eGFR over time. RESULTS: The study sample included 2212 long-COVID patients. Median age was 56 years, 51% were male. Half (∼47%-50%) of the study sample had normal eGFR (≥90 mL/min/1.73 m2) from COVID-19 diagnosis to 12 months post-COVID and <5% of patients had an eGFR <30 mL/min/1.73 m2. There was an estimated 2.96 mL/min/1.73 m2 decrease in eGFR within 1 year after COVID-19 infection that was equivalent to 3.39% reduction from the baseline. Decline in eGFR was highest in patients hospitalized for COVID-19 (6.72%) followed by diabetic patients (6.15%). More than 40% of patients were at risk of CKD. CONCLUSIONS: People with long-COVID experienced a substantial decline in eGFR within 1 year from the infection date. The prevalence of proteinuria appeared to be high. Close monitoring of kidney function is prudent among patients with persistent COVID-19 symptoms.

Kidney function and the comparative effectiveness and safety of direct oral anticoagulants vs. warfarin in adults with atrial fibrillation: a multicenter observational study.

AIMS: The aim of this study was to determine the comparative effectiveness and safety of direct oral anticoagulants (DOACs) and warfarin in adults with atrial fibrillation (AF) by level of kidney function. METHODS AND RESULTS: We pooled findings from five retrospective cohorts (2011-18) across Australia and Canada of adults with; a new dispensation for a DOAC or warfarin, an AF diagnosis, and a measure of baseline estimated glomerular filtration rate (eGFR). The outcomes of interest, within 1 year from the cohort entry date, were: (1) the composite of all-cause death, first hospitalization for ischaemic stroke, or transient ischaemic attack (effectiveness), and (2) first hospitalization for major bleeding defined as an intracranial, upper or lower gastrointestinal, or other bleeding (safety). Cox models were used to examine the association of a DOAC vs. warfarin with outcomes, after 1:1 matching via a propensity score. Kidney function was categorized as eGFR ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. A total of 74 542 patients were included in the matched analysis. DOAC initiation was associated with greater or similar effectiveness compared with warfarin initiation across all eGFR categories [pooled HRs (95% CIs) for eGFR categories: 0.74(0.69-0.79), 0.76(0.54-1.07), 0.68(0.61-0.75) and 0.86(0.76-0.98)], respectively. DOAC initiation was associated with lower or similar risk of major bleeding than warfarin initiation [pooled HRs (95% CIs): 0.75(0.65-0.86), 0.81(0.65-1.01), 0.82(0.66-1.02), and 0.71(0.52-0.99), respectively). Associations between DOAC initiation, compared with warfarin initiation, and study outcomes were not modified by eGFR category. CONCLUSION: DOAC use, compared with warfarin use, was associated with a lower or similar risk of all-cause death, ischaemic stroke, and transient ischaemic attack and also a lower or similar risk of major bleeding across all levels of kidney function.

Latent Tuberculosis Therapy Outcomes in Dialysis Patients: A Retrospective Cohort.

RATIONALE & OBJECTIVES: Maintenance dialysis patients are at an increased risk for active tuberculosis (TB). In 2012, British Columbia, Canada, began systematically screening maintenance dialysis patients for latent TB infection (LTBI) and treating people with evidence of LTBI when appropriate. We examined LTBI treatment outcomes and compared treatment outcomes before and after rollout of the systematic screening program. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: The study comprised 365 people in British Columbia, Canada, initiating at least 90 days of dialysis from January 1, 2001, to May 31, 2017, and starting LTBI therapy: 290 (79.5%) people in the recent cohort and 75 (20.5%) in the historical cohort. People starting LTBI therapy from January 1, 2012, onward were classified as the recent cohort, whereas people starting LTBI therapy before January 1, 2012, were classified as the historical cohort. EXPOSURE: Systematic LTBI screening and therapy. OUTCOMES: Proportion of people who experience grade 3 to 5 adverse events (AEs) or any grade rash and end-of-treatment outcomes. ANALYTICAL APPROACH: Outcomes were reported using descriptive statistics. 2-sample test of proportions using χ2 distribution was used to test for statistical significance between the recent and historical cohorts. RESULTS: 298 (81.6%) people successfully completed LTBI therapy. The proportion of people experiencing a grade 3 to 4 AE or any grade rash was 21.1%. Most AEs were related to gastrointestinal events, general malaise, or pruritus that resulted in regimen changes. 2 (0.5%) people were hospitalized for AEs related to LTBI therapy. No significant difference was found between the recent and historical cohorts in all outcomes of interest. No grade 5 AEs (deaths) were attributed to LTBI therapy. LIMITATIONS: Retrospective data and generalizability outside low-TB-burden settings. CONCLUSIONS: Our findings suggest that a high proportion of people receiving maintenance dialysis can complete LTBI therapy. The rate of grade 3 to 4 AEs was high and associated with frequent medication changes during therapy. LTBI therapy in maintenance dialysis may be safe but requires close monitoring.

Advancing Palliative Care in Patients With CKD: From Ideas to Practice.

A palliative approach to care focuses on what matters most to patients with life-limiting illness, including chronic kidney disease (CKD). Despite recent publication of related clinical practice guidelines in nephrology, there is limited information about how to practically implement these recommendations. In this Perspective, we describe our experience integrating a palliative approach within routine care of patients with CKD glomerular filtration rate categories 4 and 5 (G4-G5) across a provincial kidney care network during the past 15 years. The effort was led by a multidisciplinary group, tasked with building capacity and developing tools and resources for practical integration within a provincial network structure. We used an evidence-based framework that includes recommendations for 4 pillars of palliative care to guide our work: (1) patient identification, (2) advance care planning, (3) symptom assessment and management, and (4) caring of the dying patient and bereavement. Activities within each pillar have been iteratively implemented across all kidney care programs using existing committees and organizational structures. Key quality indicators were used to guide strategic planning and improvement. We supported culture change through the use of multiple strategies simultaneously. Altogether, we established and integrated palliative care activities into routine CKD G4-G5 care across the continuum from nondialysis to dialysis populations.

Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate.

Patients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m2. Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m2 and 168 mg/g, respectively. Using competing-risk regression, random-effect meta-analysis, and Markov processes with Monte Carlo simulations, we developed two- and four-year models of the probability and timing of kidney failure requiring kidney replacement therapy (KRT), a non-fatal CVD event, and death according to age, sex, race, eGFR, albumin-to-creatinine ratio, systolic blood pressure, smoking status, diabetes mellitus, and history of CVD. Hypothetically applied to a 60-year-old white male with a history of CVD, a systolic blood pressure of 140 mmHg, an eGFR of 25 ml/min/1.73m2 and a urine albumin-to-creatinine ratio of 1000 mg/g, the four-year model predicted a 17% chance of survival after KRT, a 17% chance of survival after a CVD event, a 4% chance of survival after both, and a 28% chance of death (9% as a first event, and 19% after another CVD event or KRT). Risk predictions for KRT showed good overall agreement with the published kidney failure risk equation, and both models were well calibrated with observed risk. Thus, commonly-measured clinical characteristics can predict the timing and occurrence of clinical outcomes in patients with severely decreased GFR.

Long-term patient and kidney survival after coronary artery bypass grafting, percutaneous coronary intervention, or medical therapy for patients with chronic kidney disease: a propensity-matched cohort study.

BACKGROUND: Revascularization in patients with chronic kidney disease (CKD) and coronary artery disease (CAD) is often deferred because of concern over progression of renal failure. HYPOTHESIS: Revascularization with either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) leads to progression of renal failure, but improves survival compared with medical therapy in patients with CKD. PATIENTS AND METHODS: Linkages between the British Columbia Cardiac Registry and the British Columbia Renal Registry of patients with established CAD and CKD who underwent CABG, PCI, or were treated medically were propensity matched. Overall patient survival was analyzed using a Cox proportional hazard model. Primary renal outcomes, defined as patients requiring long-term dialysis or progressive loss in kidney function, were analyzed using a competing risk approach. RESULTS: On the basis of the matched cohort, the risk of renal outcome in the first three months was the highest in the CABG group, but comparable between the PCI and the medical group (estimated probability at 3 months: 12.7% for CABG, 5.4% for PCI, 4.4% for medical; P<0.01). The estimated probability for the renal outcome at 24 months was similar across the groups: 37.9% for CABG, 37.6% for PCI, and 35.2% for medical therapy (P=0.62). The mortality risk at 24 months was lower for CABG (3.9%) compared with PCI (14.5%) or medical therapy (16.4%) (P<0.01). CONCLUSION: In patients with CAD and CKD who undergo the current practice of CABG, PCI, or are treated with medical therapy, progression of renal failure is higher in the first 3 months for CABG, but similar for all groups at 24 months. The 2-year mortality is lower in patients treated with CABG compared with PCI or medical therapy.

External validation and clinical utility of a prediction model for 6-month mortality in patients undergoing hemodialysis for end-stage kidney disease.

BACKGROUND: End-stage kidney disease is associated with poor prognosis. Health care professionals must be prepared to address end-of-life issues and identify those at high risk for dying. A 6-month mortality prediction model for patients on dialysis derived in the United States is used but has not been externally validated. AIM: We aimed to assess the external validity and clinical utility in an independent cohort in Canada. DESIGN: We examined the performance of the published 6-month mortality prediction model, using discrimination, calibration, and decision curve analyses. SETTING/PARTICIPANTS: Data were derived from a cohort of 374 prevalent dialysis patients in two regions of British Columbia, Canada, which included serum albumin, age, peripheral vascular disease, dementia, and answers to the "the surprise question" ("Would I be surprised if this patient died within the next year?"). RESULTS: The observed mortality in the validation cohort was 11.5% at 6 months. The prediction model had reasonable discrimination (c-stat = 0.70) but poor calibration (calibration-in-the-large = -0.53 (95% confidence interval: -0.88, -0.18); calibration slope = 0.57 (95% confidence interval: 0.31, 0.83)) in our data. Decision curve analysis showed the model only has added value in guiding clinical decision in a small range of threshold probabilities: 8%-20%. CONCLUSION: Despite reasonable discrimination, the prediction model has poor calibration in this external study cohort; thus, it may have limited clinical utility in settings outside of where it was derived. Decision curve analysis clarifies limitations in clinical utility not apparent by receiver operating characteristic curve analysis. This study highlights the importance of external validation of prediction models prior to routine use in clinical practice.

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. 2187 patients with CKD (eGFR 15-45 ml/min/m2) from 25 Canadian centres were divided into GN vs non-GN cause of CKD. Patients on immunotherapy for GN were not included in the study. Standardized measures of CV risk factors, biomarkers and CV outcomes were recorded over 3 years of follow-up, with the primary outcome measure being time to first all-cause CV event. RESULTS: In the overall cohort, CV events occurred in 25 (8.7%) of the GN group and 338 (17.8%) of the non-GN group (HR 0.45, 95% CI 0.30-0.67, p < 0.01). In a Cox regression multivariable model that included age, sex, prior diabetes and CVD, baseline eGFR and onset of renal replacement therapy, the risk of CV events was similar in the GN and non-GN groups (HR 0.71, 95% CI 0.47-1.08, p = 0.11). GN and non-GN patients were matched by age and using a propensity score including sex, prior diabetes and CVD and baseline eGFR. In the matched group, the risk of CV events was similar in GN vs non-GN patients (N = 25/271 (9.2%) in both groups, HR 1.01, 95% CI 0.05-1.77, p = 0.9). An interaction analysis showed that CRP, ACR and troponin conferred differing amounts of CV risk in the GN and non-GN groups. CONCLUSIONS: Patients with advanced CKD due to GN have a high 8.7% absolute 3-year risk of CVD, attributable to prior CV risk factors and level of kidney function rather than the GN disease itself.

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. The outcome of interest was mortality before commencing dialysis. The biomarker profile consisted of N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin I (TnI), asymmetric dimethylarginine (ADMA), interleukin (IL)-6, high sensitivity C-reactive protein, fibroblast growth factor-23 (FGF23), transforming growth factor-beta, 25-hydroxylvitamin D, and cystatin C (CysC). RESULTS: The mean estimated glomerular filtration rate was 27 mL/min/1.73 m2 and median follow-up time was 44 months. Mortality before dialysis commencement was the greatest in DKD (20%), followed by PCK/TIN (13%), and was least in those GN (8%). The majority of deaths were cardiovascular in nature, 17, 9, and 5.5% for DKD, PCK/TIN, GN, respectively. Those with DKD had higher hazard for mortality, unadjusted (hazard ratio [HR] 2.7, 95% CI 1.7-4.3) and adjusted (HR 1.7, 95% CI 1.1-2.8). The biomarker profiles associated with mortality differed significantly by CKD etiology as follows: DKD was associated with CysC (HR 1.3, 95% CI 1.0-1.6), ADMA (HR 1.3, 95% CI 1.1-1.6), and NT-proBNP (HR 1.7, 95% CI 1.4-2.1), GN was associated with FGF23 (HR 1.8, 95% CI 1.1-2.8), TnI (HR 3.6, 95% CI 1.3-9.5), and transforming growth factor-beta (HR 0.6, 95% CI 0.4-0.9) and PCK/TIN was associated with ADMA (HR 1.5, 95% CI 1.3-1.8) and IL-6 (HR 2.1, 95% CI 1.5-3.1). CONCLUSIONS: Biomarkers profiles differ according to the etiology of CKD and are associated with mortality.

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. DESIGN: Retrospective observational cohort study. SETTING: British Columbia, Canada, chronic renal disease registry 1995-2012. PATIENTS: 37 biopsy proven Alport syndrome or hematuria with family history of Alport syndrome. MEASUREMENTS: Serial estimated glomerular filtration rate (eGFR) Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient's eGFR measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m2 /y decline), stable state (0-2 mL/min/1.73 m2 /y decline), and regressors (>2 mL/min/1.73 m2 /y incline). METHODS: In this retrospective observational cohort study, participants were identified through a chronic renal disease registry in British Columbia, Canada, from 1995 to 2012. Inclusion criteria were biopsy proven or hematuria with a family history of Alport syndrome. Individual patients and family group members were studied. Trajectory of renal decline described graphically by fitting a cubic smoothing spline to patient's serial estimated glomerular filtration rate (eGFR) measures. Various time points within a trajectory were indexed, randomly sampled, and followed for 2 years to estimate portion of progressors (>5 mL/min/1.73 m2/y decline), stable state (0-2 mL/min/1.73 m2/y decline), and regressors (>2 mL/min/1.73 m2/y incline). LIMITATIONS: Histological or genetic evidence of Alport syndrome is not available in all patients. RESULTS: Median follow-up time was 48.2 months of 37 patients (78% male), with a median age of 36 (interquartile range [IQR], 18-47) and a median age of renal replacement therapy commencement (n = 23) of 38 (IQR = 20-52). Renal function changes were found to be heterogeneous overall, intra-individual and within families. Portion of progressors in eGFR 45-60 mL/min/1.73 m2 was 73.7% (SD, 10.3), whereas 23.6% (SD, 11.0) remained stable. Within eGFR 30-45 mL/min/1.73 m2, 45.6% (SD, 7.0) were progressors, whereas 53.4% (SD, 7.4) remained stable. A large portion of eGFR 15-30 mL/min/1.73 m2 patients were stable (54.8%; SD, 8.4), whereas 25.7% (SD, 7.1) progressed and 19.5% (SD, 5.6) regressed. CONCLUSIONS: The renal decline in Alport syndrome patients is heterogeneous which has implications for designing clinical trials of interventions.

MISE EN CONTEXTE: Les patients atteints du syndrome d'Alport voient souvent leur état de santé évoluer vers l'insuffisance rénale. La corrélation entre le génotype et le phénotype est bien établie. Par contre, l'histoire naturelle de la trajectoire menant à l'insuffisance rénale demeure mal connue. OBJECTIFS DE L'ÉTUDE: Le principal objectif de cette étude était de caractériser l'histoire naturelle du déclin de la fonction rénale chez une cohorte de patients atteints du syndrome d'Alport. CADRE ET TYPE D'ÉTUDE: Une étude de cohorte observationnelle rétrospective effectuée entre 1995 et 2012 à partir du registre provincial des maladies rénales chroniques de la Colombie-Britannique, au Canada. PATIENTS: Une cohorte de 37 patients dont le diagnostic avait été confirmé par biopsie ou qui présentaient une hématurie conjointement à un historique familial de syndrome d'Alport. MESURES: Le débit de filtration glomérulaire estimé (DFGe) a été mesuré à plusieurs reprises. La trajectoire du déclin de la fonction rénale a été représentée graphiquement en ajustant une méthode d'interpolation cubique par splines de lissage à la série de mesures du débit de filtration glomérulaire estimé (eGFR) du patient. Plusieurs périodes suivant une trajectoire déterminée ont été indexées, échantillonnées aléatoirement et suivies pendant deux ans afin d'évaluer la proportion de cas de progression de la maladie (>5 mL/min/173m2/année de déclin), de patients stationnaires (0 à 2 mL/min/1,73 m2/année de déclin) et de cas de régression (>2 mL/min/1,73 m2/année de remontée). MÉTHODOLOGIE: Les patients qui ont participé à cette étude de cohorte observationnelle et rétrospective ont été recrutés entre 1995 et 2012 au sein d'un registre des patients souffrant d'insuffisance rénale chronique de la Colombie-Britannique, au Canada. La sélection des participants s'est effectuée sur la base d'un diagnostic posé par biopsie OU d'une hématurie en présence d'un historique familial de syndrome d'Alport. Les patients eux-mêmes, ainsi que des membres de leurs familles respectives ont été observés. La trajectoire du déclin de la fonction rénale a été représentée graphiquement en ajustant une méthode d'interpolation cubique par splines de lissage à la série de mesures du débit de filtration glomérulaire estimé (eGFR) du patient. Plusieurs périodes suivant une trajectoire déterminée ont été indexées, échantillonnées aléatoirement et suivies pendant deux ans afin d'évaluer la proportion de cas de progression de la maladie (>5 mL/min/173m2/année de déclin), de patients stationnaires (0 à 2 mL/min/1,73m2/année de déclin) et de cas de régression (>2 mL/min/1,73m2/année de remontée). LIMITES DE L'ÉTUDE: Les données génétiques ou histologiques nécessaires pour la confirmation du syndrome d'Alport étaient absentes pour certains patients. RÉSULTATS: Le suivi s'est effectué auprès de 37 patients dont 78% étaient des hommes et s'est échelonné sur une période moyenne de 48,2 mois. L'âge médian des participants était de 36 ans (Ecart Interquartile [EI] 18, 47) et l'âge médian où ceux-ci avaient commencé une thérapie de remplacement de la fonction rénale était de 38 ans (EI 20, 52). Les changements dans la fonction rénale se sont avérés hétérogènes tant de façon globale pour l'étude que chez les individus ou au sein de leurs familles. La proportion de progression de la maladie pour les patients présentant des valeurs de eGFR entre 45 et 60 mL/min/1,73m2 était de 73,7% (Écart-type [ÉT]: 10,3) tandis que 23,6% (ÉT: 11,0) sont demeurés stables. Dans le groupe de patients dont les valeurs de eGFR se situaient entre 30 et 45 mL/min/1,73m2, une proportion de 45,6% (ÉT: 7,0) était en progression alors que 53,4% (ÉT: 7,4) sont demeurés stables. Une forte proportion des patients présentant des valeurs de eGFR entre 15 et 30 mL/min/1,73m2 soit 54,8% (ÉT: 8,4) sont demeurés stables, tandis que 25,7% (ÉT: 7,1) étaient en progression et 19,5% (ÉT: 5,6) étaient en régression. CONCLUSIONS: Le déclin de la fonction rénale chez les patients atteints du syndrome d'Alport est hétérogène ce qui entraîne des répercussions sur la façon de concevoir les essais d'intervention cliniques.

Time to revisit the problem of CIN? The low incidence of acute kidney injury with and without contrast in hospitalized patients: an observational cohort study.

BACKGROUND: Acute kidney injury (AKI) following imaging procedures with contrast medium in hospitalized patients is commonly attributed to contrast-induced nephropathy (CIN). This study sought to establish a benchmark of the incidence of AKI in hospitalized patients who underwent computed tomography (CT) scans, with and without intravenous contrast administration. METHODS: This was a multi-center observational cohort study. Hospitalized patients in four hospitals with CT scans during two time periods in 2012 and 2013 were included. AKI post-scan was defined as a change in serum creatinine (sCr) in absolute terms of ≥26.5 µmol/L (≥0.3 mg/dl), occurring within 7 days of the CT scan. AKI incidence was examined by study phases and CT-scan types using logistic regression models. Multinomial logistic regression was used to examine the proportions of sCr availability between two study phases. RESULTS: Three hundred and twenty-five patients in Period 1 and 518 patients in Period 2 were included in the study. The incidence of AKI in Period 1 was similar in those who received contrast and in those who did not (11.6 % [95 % C.I.: 6.5, 18.7] vs. 10.1 % [95 % C.I.: 5.1, 17.3]; p = 0.38). The incidence of AKI remained not significantly different between the two periods in those who received contrast (11.6 % [95 % C.I.: 6.5, 18.7] vs. 10.7 % [95 % C.I.: 6.8, 15.8]; p = 0.89) and those who did not (10.1 % [95 % C.I.: 5.1, 17.3] vs. 9.1 % [95 % C.I.: 5.2, 14.6]; p = 0.54). Among those who received contrast, there was a significant increase in the availability of both pre- and post- CT scan sCr in Period 2 compared to Period 1 (73.6 % [95 % C.I.: 67.7, 80.6] vs. 79.8 % [95 % C.I.: 75.2, 84.7]; p = 0.006). LIMITATIONS: Our study was not targeted to specifically assess the impact of a prevention protocol on the incidence of AKI and was limited to settings within one health authority in the province. CONCLUSION: In hospitalized patients, the incidence of AKI is low, not different between those who did and did not receive contrast, and was not impacted by improvement in the monitoring of sCr in at risk patients. A better understanding of the determinants of AKI post-contrast scan is required to improve strategies to reduce the incidence of AKI.

DONNÉES CONNUES: L'occurrence d'un épisode d'insuffisance rénale aiguë (IRA) à la suite d'examens d'imagerie médicale avec administration d'un agent de contraste est fréquemment attribuée à une néphropathie induite par l'agent de contraste lui-même. La présente étude a cherché à établir des bases de référence susceptibles d'aider à mesurer l'incidence des épisodes d'IRA chez les patients hospitalisés qui ont à subir un examen par tomodensitométrie (scanner), avec ou sans administration intraveineuse d'un agent de contraste. MÉTHODOLOGIE: Cette étude observationnelle a été réalisée sur des cohortes de patients hospitalisés sélectionnés dans les unités de néphrologie de quatre centres hospitaliers différents. Ces patients ont subi des examens par tomodensitométrie au cours de deux périodes distinctes en 2012 et en 2013. Il a été décrété que les patients étaient atteints de néphropathie post-scanner lorsque leur taux de créatinine sérique augmentait de plus de 26.5 µmol/L ou à 0.3 mg/dl dans les 7 jours suivant l'examen. L'incidence d'insuffisance rénale aiguë a été analysée à l'aide d'un modèle de régression logistique en fonction de la phase de l'étude et du type de tomodensitomètre utilisé pour l'examen. Une régression logistique multinomiale a été utilisée pour présenter les taux de créatinine sérique mesurés entre les phases de l'étude. RÉSULTATS: La cohorte de la phase 1 comptait 325 patients et celle de la phase 2 en comptait 518. Il en est ressorti que l'incidence d'IRA post-scanner était similaire chez tous les patients de la phase 1, qu'ils aient ou non reçu un agent de contraste par intraveineuse avant l'examen (11.6 % [95 % I.C: 6.5, 18.7] vs 10.1 % [95 % I.C: 5.1, 17.3]; p = 0.38). L'incidence des épisodes d'IRA post-scanner est demeurée similaire dans les deux phases pour les patients ayant reçu un agent de contraste (11.6 % [95 % I.C: 6.5, 18.7] vs 10.7 % [95 % I.C: 6.8, 15.8]; p = 0.89) de même pour les patients n'en ayant pas reçu (10.1 % [95 % I.C: 5.1, 17.3] vs 9.1 % [95 % I.C: 5.2, 14.6]; p = 0.54). Chez les sujets ayant reçu un produit de contraste, il y avait une plus grande disponibilité des mesures de créatinine sérique pré ­ et post-scanner dans la période 2 par rapport à la période 1 (73.6 % [95 % I.C: 67.7, 80.6] vs 79.8 % [95 % I.C: 75.2, 84.7]; p = 0.006). LIMITES DE L'ÉTUDE: La présente étude ne visait pas à évaluer de façon systématique l'impact d'un protocole de prévention sur l'incidence d'un épisode d'IRA, étant donné qu'elle s'est limitée aux paramètres établis dans un seul cadre régional. CONCLUSION: L'incidence d'un épisode d'IRA chez les patients hospitalisés subissant un examen en tomodensitométrie demeure faible, et n'apparait pas significativement différente qu'ils reçoivent ou non un agent de contraste au préalable. Une surveillance plus rigoureuse des taux de créatinine sérique chez les patients à risque n'a pas non plus mené à des différences marquées dans l'incidence d'un épisode d'IRA post-scanner. Ainsi, une meilleure compréhension des facteurs susceptibles de provoquer des épisodes d'IRA post-scanner est requise afin d'améliorer les stratégies visant la réduction de leur incidence.

Cardiac strangulation following epicardial pacemaker implantation: a rare pediatric complication.

OBJECTIVES: The aim of our study was 2-fold: to determine the incidence of cardiac strangulation (CS) and to develop a clinical pathway to aid in the diagnosis and prognosis of CS. In <2 years, 2 cases of CS occurred in our institution, which caused much alarm and led to the study's objectives. METHODS: All patients who underwent implantation of an epicardial pacemaker from January 1992 to March 2012 were included. There were no exclusion criteria. Health records were used to locate all subjects and gather all retrospective data. Prospectively, subjects without a chest radiograph from the previous 2 years were approached for imaging. RESULTS: This study included 86 patients retrospectively, and 84 patients prospectively. There was a 2.3% incidence, and a 1.2% mortality, related to CS. A pattern of posterior looping of the ventricular lead was seen in radiographs of both CS-diagnosed patients. Five variables were significantly associated with an outcome of CS (P = .0153). CONCLUSIONS: Our data indicate that the 2 cases of CS were not caused by a lack of follow-up but by a lack of consistent imaging for diagnosis. This conclusion is supported by the 8 cases of CS found in the English-language literature. If the patient is age ≤6 months at the time of implantation, particular attention should be given to the placement of leads and follow-up.

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/1.73 m(2), under nephrology care, in urban and rural centers. We measured traditional clinical and laboratory risk factors, as well as newer biomarkers: cystatin C, high sensitivity c-reactive protein (hsCRP), interleukin 6 (IL6), transforming growth factor ß1 (TGFß1), fibroblast growth factor 23 (FGF23), N-terminal probrain natriuretic peptide (NT-proBNP), troponin I and asymmetric dimethylarginine (ADMA). Key outcomes were renal replacement therapy (RRT, dialysis or transplantation) and death, during the first year follow-up after enrollment: a time point important for clinical decision-making for patients and providers. RESULTS: Newer biomarkers do not improve the prediction of RRT, when added to conventional risk factors such as eGFR, urine albumin to creatinine ratio, hemoglobin, phosphate and albumin. However, in predicting death within 1 year, cystatin C, NT-proBNP, hsCRP and FGF23 values significantly improved model discrimination and reclassification: c statistic increased by absolute 4.3% and Net Reclassification Improvement for categories of low, intermediate and high risk at 11.2%. CONCLUSIONS: Our findings suggest that the addition of newer biomarkers may be useful in predicting death in patients with established CKD within a 1-year timeframe. This information may be useful in informing prognosis and redirect resources to serve patients at higher risk to improve outcomes and sustainability of the nephrology care system.

An overview of the British Columbia Glomerulonephritis network and registry: integrating knowledge generation and translation within a single framework.

BACKGROUND: Glomerulonephritis (GN) is a group of rare kidney diseases with a substantial health burden and high risk of progression to end-stage renal disease. Research in GN has been limited by poor availability of large comprehensive registries. Substantial variations in access to and administration of treatment and outcomes in GN have been described. Leveraging provincial resources and existing infrastructure, the British Columbia (BC) GN Network is an initiative which serves to combine research and clinical care objectives. The goal of the BC GN Network is to coordinate and improve health care, including robust data capture, on all patients with GN in BC, a Canadian province of over 4.6 million people. This provincial initiative will serve as a model for Canadian or other national and international endeavours. DESCRIPTION: The BC Provincial Renal Agency (BCPRA) is the provincial governmental agency responsible for health delivery for all kidney patients in BC. The BC GN Network has been created by the BCPRA to ensure high quality and equitable access to care for all patients with GN and is a platform for evidence based clinical care programs and associated health policy. All patients with biopsy-proven GN are registered at the time of kidney biopsy into the BCPRA provincial database of kidney disease patients, forming the BC GN Registry. Thereafter, all laboratory results and renal related outcomes are captured automatically. Histology data and core clinical variables are entered into the database. Additional linkages between the GN Registry and administrative databases ensure robust capture of medications, hospital admissions, health care utilization, comorbidities, cancer and cardiac outcomes, and vital statistics. CONCLUSIONS: The BC GN Network and Registry is a unique model in that it combines robust data capture, data linkages, and health care delivery and evaluation into one integrated system. This model utilizes existing health infrastructure to prospectively capture population level data on patients with GN, producing a rich dataset capable of real-time identification and evaluation of GN health policy initiatives, of supporting observational cohort studies and health services research in GN, and of facilitating patient recruitment into GN clinical trials.

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. METHODS/DESIGNS: Commenced 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 (TGFß1). 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. DISCUSSION: The 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 TGFß1 values were lower at lower GFR. These distributions of each of the newer biomarkers by eGFR and uACR categories were variable.

Disease-specific risk of venous thromboembolic events is increased in idiopathic glomerulonephritis.

The risk of venous thromboembolic events is thought to be highest in patients with membranous nephropathy. This association has been recently questioned, and it is not known whether this simply reflects the severity of proteinuria. To better understand the relationship between histologic diagnosis and the risk of venous thromboembolic events we evaluated patients in the Toronto Glomerulonephritis Registry. Of 1313 patients with idiopathic glomerulonephritis, 395 were diagnosed with membranous nephropathy, 370 with focal segmental glomerulosclerosis (FSGS), and 548 with immunoglobulin-A nephropathy (IgAN). Risk factors were evaluated by Cox proportional hazards for 53 image-confirmed venous thromboembolic events in 44 patients during a median follow-up of 63 months. The risk was highest in patients with membranous nephropathy and FSGS (hazard ratios of 22 and 7.8, respectively) referenced to patients with IgAN. Following adjustment for gender, cancer history, proteinuria, and serum albumin by multivariable analysis, the histologic subtype remained an independent risk for venous thromboembolic events. This risk was still highest in patients with membranous nephropathy followed by FSGS with adjusted hazard ratios of 10.8 and 5.9, respectively. Thus, in this large cohort, histologic diagnosis was an independent risk factor for venous thromboembolic events. Further studies are needed to discover mechanisms responsible for this high risk in patients with membranous nephropathy.

Evaluation and treatment of CKD patients before and at their first nephrologist encounter in Canada.

BACKGROUND: Much of the comorbidity associated with chronic kidney disease (CKD) begins in the early stages. Interventions with proven efficacy exist to decrease progression, morbidity, and mortality. This study examines their use in patients with CKD before and at their first nephrologist encounter in Canada. STUDY DESIGN: Prospective multicenter cohort study. SETTING & PARTICIPANTS: 482 patients at their first nephrologist encounter enrolled from 13 Canadian centers. Inclusion criteria were measured or estimated glomerular filtration rate less than 50 mL/min/1.73 m(2). Exclusion criteria were patients with acute kidney failure or those likely to require dialysis therapy within 3 months of referral. OUTCOMES & MEASUREMENTS: Describe: (1) characteristics of patients at their first nephrology encounter in Canada; (2) the evaluation for cardiac risk factors, cardiac diseases and CKD complications and their management before the encounter; (3) changes in management initiated by nephrologists at the first encounter; and (4) the availability and use of allied health professional services for CKD care. RESULTS: Patients had a mean age of 69.7 years, estimated glomerular filtration rate of 29 mL/min/1.73 m(2) (0.48 mL/s/1.73 m(2), hemoglobin level of 12.1 g/dL (121 g/L), albumin level of 3.6 g/dL (36 g/L), and blood pressure of 147/76 mm Hg. Transmission of results from prior evaluation was variable. At the encounter, nephrologists had available or ordered albumin and calcium/phosphate tests in greater than 70% of patients. Nephrologists did not evaluate parathyroid hormone in 83% of patients, lipids in greater than 50%, iron studies (in those with anemia) in 57%, and urine studies in 30%. Despite a high prevalence of diabetes and coronary artery disease, only 46% were administered medications to interrupt the renin-angiotensin system, 37% were administered acetylsalicylic acid, and 32% were administered lipid medication after the encounter. Availability and use of allied health professional resources varied and was low in an unstructured setting. LIMITATIONS: External validity, referral bias, and inability to make causal inferences. CONCLUSIONS: In Canada, patients with CKD continue to be encountered late by nephrologists (stage IV CKD). Information for prior evaluation is incompletely transmitted. Finally, there appears to be room for improvement in evaluation and treatment at the first nephrologist encounter.

Evaluation of predictive formulae for glomerular filtration rate for carboplatin dosing in gynecological malignancies.

OBJECTIVES: Carboplatin dosing is usually based on glomerular filtration rate (GFR). The Cockcroft-Gault and the Modified Diet in Renal Disease (MDRD) Study formulae are based on serum creatinine to estimate GFR when measured GFR is impractical. The MDRD formula has been shown to be more accurate in non-cancer patients with chronic renal disease. We compared the accuracy of these formulae for dosing carboplatin in patients with gynecological cancers. METHODS: Patient data were collected retrospectively at the Vancouver Centre of the British Columbia Cancer Agency, Canada. GFR estimated by formula was compared to measured GFR. Dose derived from estimated GFR was compared to dose derived from measured GFR. Bias (percentage error) and precision (absolute percentage error) were compared with two-sided paired t-test. RESULTS: A total of 96 patients were evaluable: median age 60 years, weight 62 kg, height 159 cm, baseline serum creatinine 71 micromol/l, GFR 91 ml/min. Both formulae had limited precision with a small bias for estimated GFR and dosing. Eight-five percent of patients would have received a significantly different dose if estimated GFR from any formula was used. The MDRD formula was more precise than the Cockcroft-Gault formula. CONCLUSIONS: The MDRD formula seems to be more accurate than the Cockcroft-Gault formula in this population. However, both have limited precision and measured GFR should be preferred for carboplatin dosing.