Hospital and Physician Variability in Revascularization Decisions and Outcomes for Patients With 3-Vessel and Left Main Coronary Artery Disease: A Population-Based Cohort Study.

BACKGROUND: Hospital- and physician-level variation for selection of percutaneous coronary intervention versus coronary artery bypass grafting (CABG) for patients with coronary artery disease has been associated with outcome differences. However, most studies excluded patients treated medically. METHODS AND RESULTS: From 2010 to 2019, adults with 3-vessel or left main coronary artery disease at 3 hospitals (A, B, C) in Alberta, Canada, were categorized by treatment with medical therapy, percutaneous coronary intervention, or CABG. Multilevel regression models determined the proportion of variation in treatment attributable to patient, physician, and hospital factors, and survival models assessed outcomes including death and major adverse cardiovascular events over 5 years. Of 22 580 patients (mean age, 67 years; 80% men): 6677 (29%) received medical management, 9171 (41%) percutaneous coronary intervention, and 6732 (30%) CABG. Hospital factors accounted for 10.8% of treatment variation. In adjusted models (site A as reference), patients at sites B and C had 49% (95% CI, 44%-53%) and 43% (95% CI, 37%-49%) lower rates of medical therapy, respectively, and 31% (95% CI, 24%-38%) and 32% (95% CI, 24%-40%) lower rates of CABG. During 5.0 years median follow-up, 3287 (14.6%) patients died, with no intersite mortality differences. There were no between-site differences in acute coronary syndromes or stroke; patients at sites B and C had 24% lower risk (95% CI, 13%-34% and 11%-35%, respectively) of heart failure hospitalization. CONCLUSIONS: Hospital-level variation in selection of percutaneous coronary intervention, CABG, or medical therapy for patients with complex coronary artery disease was not associated with differences in 5-year mortality rates. Research and quality improvement initiatives comparing revascularization practices should include medically managed patients.

Recovery of kidney function after acute kidney disease-a multi-cohort analysis.

BACKGROUND: There are no consensus definitions for evaluating kidney function recovery after acute kidney injury (AKI) and acute kidney disease (AKD), nor is it clear how recovery varies across populations and clinical subsets. We present a federated analysis of four population-based cohorts from Canada, Denmark and Scotland, 2011-18. METHODS: We identified incident AKD defined by serum creatinine changes within 48 h, 7 days and 90 days based on KDIGO AKI and AKD criteria. Separately, we applied changes up to 365 days to address widely used e-alert implementations that extend beyond the KDIGO AKI and AKD timeframes. Kidney recovery was based on resolution of AKD and a subsequent creatinine measurement below 1.2× baseline. We evaluated transitions between non-recovery, recovery and death up to 1 year; within age, sex and comorbidity subgroups; between subset AKD definitions; and across cohorts. RESULTS: There were 464 868 incident cases, median age 67-75 years. At 1 year, results were consistent across cohorts, with pooled mortalities for creatinine changes within 48 h, 7 days, 90 days and 365 days (and 95% confidence interval) of 40% (34%-45%), 40% (34%-46%), 37% (31%-42%) and 22% (16%-29%) respectively, and non-recovery of kidney function of 19% (15%-23%), 30% (24%-35%), 25% (21%-29%) and 37% (30%-43%), respectively. Recovery by 14 and 90 days was frequently not sustained at 1 year. Older males and those with heart failure or cancer were more likely to die than to experience sustained non-recovery, whereas the converse was true for younger females and those with diabetes. CONCLUSION: Consistently across multiple cohorts, based on 1-year mortality and non-recovery, KDIGO AKD (up to 90 days) is at least prognostically similar to KDIGO AKI (7 days), and covers more people. Outcomes associated with AKD vary by age, sex and comorbidities such that older males are more likely to die, and younger females are less likely to recover.

Unsupervised item response theory models for assessing sample heterogeneity in patient-reported outcomes measures.

PURPOSE: Unsupervised item-response theory (IRT) models such as polytomous IRT based on recursive partitioning (IRTrees) and mixture IRT (MixIRT) models can be used to assess differential item functioning (DIF) in patient-reported outcome measures (PROMs) when the covariates associated with DIF are unknown a priori. This study examines the consistency of results for IRTrees and MixIRT models. METHODS: Data were from 4478 individuals in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry who received cardiac angiography in Alberta, Canada, and completed the Hospital Anxiety and Depression Scale (HADS) depression subscale items. The partial credit model (PCM) based on recursive partitioning (PCTree) and mixture PCM (MixPCM) were used to identify covariates associated with differential response patterns to HADS depression subscale items. Model covariates included demographic and clinical characteristics. RESULTS: The median (interquartile range) age was 64.5(15.7) years, and 3522(78.5%) patients were male. The PCTree identified 4 terminal nodes (subgroups) defined by smoking status, age, and body mass index. A 3-class PCM fits the data well. The MixPCM latent classes were defined by age, disease indication, smoking status, comorbid diabetes, congestive heart failure, and chronic obstructive pulmonary disease. CONCLUSION: PCTree and MixPCM were not consistent in detecting covariates associated with differential interpretations of PROM items. Future research will use computer simulations to assess these models' Type I error and statistical power for identifying covariates associated with DIF.

Follow-up Care of Critically Ill Patients With Acute Kidney Injury: A Cohort Study.

Rationale & Objective: To evaluate follow-up care of critically ill patients with acute kidney injury (AKI). Study Design: Retrospective cohort study. Setting & Participants: Patients admitted to the intensive care unit (ICU) with AKI in Alberta, Canada from 2005 to 2018, who survived to discharge without kidney replacement therapy or estimated glomerular filtration rate <15 mL/min/1.73 m2. Exposure: AKI (defined as ≥50% or ≥0.3 mg/dL serum creatinine increase). Outcomes: The primary outcome was the cumulative incidence of an outpatient serum creatinine and urine protein measurement at 3 months postdischarge. Secondary outcomes included an outpatient serum creatinine or urine protein measurement or a nephrologist visit at 3 months postdischarge. Analytical Approach: Patients were followed from hospital discharge until the first of each outcome of interest, death, emigration from the province, kidney replacement therapy (maintenance dialysis or kidney transplantation), or end of study period (March 2019). We used non-parametric methods (Aalen-Johansen) to estimate the cumulative incidence functions of outcomes accounting for competing events (death and kidney replacement therapy). Results: There were 29,732 critically ill adult patients with AKI. The median age was 68 years (IQR, 57-77), 39% were female, and the median baseline estimated glomerular filtration rate was 72 mL/min/1.73 m2 (IQR, 53-90). The cumulative incidence of having an outpatient creatinine and urine protein measurement at 3 months postdischarge was 25% (95% CI, 25-26). At 3 months postdischarge, 64% (95% CI, 64-65) had an outpatient creatinine measurement, 28% (95% CI, 27-28) had a urine protein measurement, and 5% (95% CI, 4-5) had a nephrologist visit. Limitations: We lacked granular data, such as urine output. Conclusions: Many critically ill patients with AKI do not receive the recommended follow-up care. Our findings highlight a gap in the transition of care for survivors of critical illness and AKI.

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.

Prediction of major postoperative events after non-cardiac surgery for people with kidney failure: derivation and internal validation of risk models.

BACKGROUND: People with kidney failure often require surgery and experience worse postoperative outcomes compared to the general population, but existing risk prediction tools have excluded those with kidney failure during development or exhibit poor performance. Our objective was to derive, internally validate, and estimate the clinical utility of risk prediction models for people with kidney failure undergoing non-cardiac surgery. DESIGN, SETTING, PARTICIPANTS, AND MEASURES: This study involved derivation and internal validation of prognostic risk prediction models using a retrospective, population-based cohort. We identified adults from Alberta, Canada with pre-existing kidney failure (estimated glomerular filtration rate [eGFR] < 15 mL/min/1.73m2 or receipt of maintenance dialysis) undergoing non-cardiac surgery between 2005-2019. Three nested prognostic risk prediction models were assembled using clinical and logistical rationale. Model 1 included age, sex, dialysis modality, surgery type and setting. Model 2 added comorbidities, and Model 3 added preoperative hemoglobin and albumin. Death or major cardiac events (acute myocardial infarction or nonfatal ventricular arrhythmia) within 30 days after surgery were modelled using logistic regression models. RESULTS: The development cohort included 38,541 surgeries, with 1,204 outcomes (after 3.1% of surgeries); 61% were performed in males, the median age was 64 years (interquartile range [IQR]: 53, 73), and 61% were receiving hemodialysis at the time of surgery. All three internally validated models performed well, with c-statistics ranging from 0.783 (95% Confidence Interval [CI]: 0.770, 0.797) for Model 1 to 0.818 (95%CI: 0.803, 0.826) for Model 3. Calibration slopes and intercepts were excellent for all models, though Models 2 and 3 demonstrated improvement in net reclassification. Decision curve analysis estimated that use of any model to guide perioperative interventions such as cardiac monitoring would result in potential net benefit over default strategies. CONCLUSIONS: We developed and internally validated three novel models to predict major clinical events for people with kidney failure having surgery. Models including comorbidities and laboratory variables showed improved accuracy of risk stratification and provided the greatest potential net benefit for guiding perioperative decisions. Once externally validated, these models may inform perioperative shared decision making and risk-guided strategies for this population.

Perioperative management for people with kidney failure receiving dialysis: A scoping review.

BACKGROUND: People with kidney failure receiving dialysis (CKD-G5D) are more likely to undergo surgery and experience poorer postoperative outcomes than those without kidney failure. In this scoping review, we aimed to systematically identify and summarize perioperative strategies, protocols, pathways, and interventions that have been studied or implemented for people with CKD-G5D. METHODS: We searched MEDLINE, EMBASE, CINAHL Plus, Cochrane Database of Systematic Reviews, and Cochrane Controlled Trials registry (inception to February 2020), in addition to an extensive grey literature search, for sources that reported on a perioperative strategy to guide management for people with CKD-G5D. We summarized the overall study characteristics and perioperative management strategies and identified evidence gaps based on surgery type and perioperative domain. Publication trends over time were assessed, stratified by surgery type and study design. RESULTS: We included 183 studies; the most common study design was a randomized controlled trial (27%), with 67% of publications focused on either kidney transplantation or dialysis vascular access. Transplant-related studies often focused on fluid and volume management strategies and risk stratification, whereas dialysis vascular access studies focused most often on imaging. The number of publications increased over time, across all surgery types, though driven by non-randomized study designs. CONCLUSIONS: Despite many current gaps in perioperative research for patients with CKD-G5D, evidence generation supporting perioperative management is increasing, with recent growth driven primarily by non-randomized studies. Our review may inform organization of evidence-based strategies into perioperative care pathways where evidence is available while also highlighting gaps that future perioperative research can address.

Association of Kidney Function With Major Postoperative Events After Noncardiac Ambulatory Surgeries: A Population-Based Cohort Study.

OBJECTIVE: The aim of this study was to estimate the association between estimated glomerular filtration rate (eGFR) and acute myocardial infarction (AMI) or death after ambulatory noncardiac surgery. SUMMARY BACKGROUND DATA: People with chronic kidney disease (CKD) commonly undergo surgical procedures. Although most are performed in an ambulatory setting, the risk of major perioperative outcomes after ambulatory surgery for people with CKD is unknown. METHODS: In this retrospective population-based cohort study using administrative health data from Alberta, Canada, we included adults with measured preoperative kidney function undergoing ambulatory noncardiac surgery between April 1, 2005 and February 28, 2017. Participants were categorized into 6 eGFR categories (in mL/min/1.73m 2 )of ≥60 (G1-2), 45 to 59 (G3a), 30 to 44 (G3b), 15 to 29 (G4), <15 not receiving dialysis (G5ND), and those receiving chronic dialysis (G5D). The odds of AMI or death within 30 days of surgery were estimated using multivariable generalized estimating equation models. RESULTS: We identified 543,160 procedures in 323,521 people with a median age of 66 years (IQR 56-76); 52% were female. Overall, 2338 people (0.7%) died or had an AMI within 30 days of surgery. Compared with the G1-2 category, the adjusted odds ratio of death or AMI increased from 1.1 (95% confidence interval: 1.0-1.3) for G3a to 3.1 (2.6-3.6) for G5D. Emergency Department and Urgent Care Center visits within 30 days were frequent (17%), though similar across eGFR categories. CONCLUSIONS: Ambulatory surgery was associated with a low risk of major postoperative events. This risk was higher for people with CKD, which may inform their perioperative shared decision-making and management.

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.

Using the Revised Cardiac Risk Index to Predict Major Postoperative Events for People With Kidney Failure: An External Validation and Update.

Background: People with kidney failure have high risk of postoperative morbidity and mortality. Although the revised cardiac risk index (RCRI) is used to estimate the risk of major postoperative events, it has not been validated in this population. We aimed to externally validate the RCRI and determine whether updating the model improved predictions for people with kidney failure. Methods: We derived a retrospective, population-based cohort of adults with kidney failure (maintenance dialysis or sustained estimated glomerular filtration rate < 15 mL/min per 1.73 m2) who had surgery in Alberta, Canada between 2005 and 2019. We categorized participants based on RCRI variables and assigned risk estimates of death or major cardiac events, and then estimated predictive performance. We re-estimated the coefficients for each RCRI variable and internally validated the updated model. Net benefit was estimated with decision curve analysis. Results: After 38,541 surgeries, 1204 events (3.1%) occurred. The estimated C-statistic for the original RCRI was 0.64 (95% confidence interval: 0.62, 0.65). Examination of calibration revealed significant risk overestimation. In the re-estimated RCRI model, discrimination was marginally different (C-statistic 0.67 [95% confidence interval: 0.66, 0.69]), though calibration was improved. No net benefit was observed when the data were examined with decision curve analysis, whereas the original RCRI was associated with harm. Conclusions: The RCRI performed poorly in a Canadian kidney failure cohort and significantly overestimated risk, suggesting that RCRI use in similar kidney failure populations should be limited. A re-estimated kidney failure-specific RCRI may be promising but needs external validation. Novel perioperative models for this population are urgently needed.

Contexte: Les personnes atteintes d'insuffisance rénale présentent un risque élevé de mortalité et de morbidité postopératoires. L'indice de risque cardiaque révisé (IRCR) est utilisé pour estimer le risque d'événements postopératoires majeurs, mais il n'a pas été validé au sein de cette po-pulation. Nous avons cherché à réaliser une validation externe de l'IRCR et à déterminer si une modification du modèle pourrait permettre une meilleure valeur prédictive pour les patients atteints d'insuffisance rénale. Méthodologie: Nous avons étudié rétrospectivement une cohorte populationnelle d'adultes atteints d'insuffisance rénale (sous dialyse d'entretien ou avec un débit de filtration glomérulaire estimé < 15 ml/min/1,73 m2, de façon soutenue) ayant subi une intervention chirurgicale en Alberta (Canada) entre 2005 et 2019. Les participants ont été classifiés selon les variables de l'IRCR, et une estimation du risque de décès ou d'événement cardiovasculaire majeur leur a été attribuée; la performance prédictive a ensuite été évaluée. Nous avons réestimé les coefficients pour chacune des variables de l'IRCR et nous avons validé de manière interne le modèle modifié. Le bénéfice net a été estimé avec une analyse de la courbe décisionnelle. Résultats: Après 38 541 interventions chirurgicales, des événements cardiovasculaires sont survenus dans 1 204 cas (3,1 %). La statistique C estimée obtenue avec l'IRCR initial était de 0,64 (intervalle de confiance [IC] à 95 %, de 0,62 à 0,65). Un examen de la calibration de l'indice a révélé une surestimation significative du risque. Avec le modèle d'IRCR modifié, la discrimination présentait une légère différence (statistique C de 0,67 [IC à 95 %, de 0,66 à 0,69]), bien que la calibration ait été améliorée. Pour l'indice modifié, aucun bénéfice net n'a été observé lors de l'examen des données par une analyse décisionnelle, alors qu'un préjudice était associé à l'IRCR initial. Conclusions: L'IRCR s'est révélé peu concluant dans une cohorte populationnelle de patients canadiens atteints d'insuffisance rénale et il a significativement surestimé les risques pour ces patients, ce qui suggère que l'utilisation de l'IRCR dans des populations similaires atteintes d'insuffisance rénale devrait être limitée. Un IRCR réestimé, propre à la population des patients atteints d'insuffisance rénale, pourrait être prometteur, mais requiert une validation externe. De nouveaux modèles périopératoires sont indispensables pour cette population.

Heart rate variability as a function of menopausal status, menstrual cycle phase, and estradiol level.

Low estradiol status is associated with increased cardiovascular risk. We sought to determine the association between heart rate variability (HRV), a marker of cardiovascular risk, at baseline and in response to stressor as a function of menopausal status, menstrual cycle phase and estradiol level. Forty-one healthy women (13 postmenopausal, 28 premenopausal) were studied. Eleven premenopausal women were additionally studied in the high and low estradiol phases of the menstrual cycle. HRV was calculated by spectral power analysis (low Frequency (LF), high frequency (HF) and LF:HF) at baseline and in response to graded Angiotensin II (AngII) infusion. The primary outcomes were differences in HRV at baseline and in response to AngII. Compared to premenopausal women in the low estradiol phase, postmenopausal women demonstrated lower baseline LF (p = 0.01) and HF (p < 0.001) measures, which were not significant after adjustment for age and BMI. In response to AngII, a decrease in cardioprotective HRV (ΔHF = -0.43 ± 0.46 ln ms2 , p = 0.005 vs. baseline) was observed in postmenopausal women versus premenopausal women. Baseline HRV parameters did not differ by menstrual phase in premenopausal women. During the low estradiol phase, no differences were observed in the HRV response to AngII challenge. In contrast, women in the high estradiol phase were unable to maintain HRV (ΔLF = -0.07 ± 0.46 ln ms2 , p = 0.048 response vs. baseline, ΔHF = -0.33 ± 0.74 ln ms2, p = 0.048 response vs. baseline). No association was observed between any measure of HRV and estradiol level. Menopausal status and the high estradiol phase in premenopausal women were associated with reduced HRV, a marker of cardiovascular risk. Understanding the role of estradiol in the modulation of cardiac autonomic tone may help guide risk reduction strategies in women.

Mortality and Resource Use Among Individuals With Chronic Kidney Disease or Cancer in Alberta, Canada, 2004-2015.

Importance: Although the public is aware that cancer is associated with excess mortality and adverse outcomes, the clinical consequences of chronic kidney disease (CKD) are not well understood. Objective: To compare the clinical consequences of incident severe CKD and the first diagnosis with a malignant tumor, focusing on the 10 leading causes of cancer in men and women residing in Canada. Design, Setting, and Participants: This population-based cohort study enrolled individuals aged 19 years and older with severe CKD or certain types of cancer between 2004 and 2015 in Alberta, Canada. Data were analyzed in November 2021. Exposures: Individuals were categorized as having severe CKD (based on estimated glomerular filtration rate <30 mL/min/1.73 m2 or nephrotic albuminuria without dialysis or kidney transplantation) or nonmetastatic or metastatic cancer (defined by a diagnosis of lung, breast, colorectal, prostate, bladder, thyroid, kidney or renal pelvis, uterus, pancreas, or oral cancer). Main Outcomes and Measures: All-cause mortality, number of hospitalizations, total number of hospital days, and placement into long-term care were calculated after diagnosis. Results: Of 200 494 individuals in the cohort (104 559 women [52.2%]; median [IQR] age, 66.8 [55.9-77.7] years), 51 159 (25.5%) had incident severe CKD, 115 504 (57.6%) had nonmetastatic cancer, and 33 831 (16.9%) had metastatic cancer. Kaplan-Meier 1-year survival was 83.3% (95% CI, 83.0%-83.6%) for patients with CKD, 91.2% (95% CI, 91.0%-91.4%) for patients with nonmetastatic cancer, and 52.8% (95% CI, 52.2%-53.3%) for patients with metastatic cancer. Kaplan-Meier 5-year survival was 54.6% (95% CI, 54.2%-55.1%) for patients with CKD, 76.6% (95% CI, 76.3%-76.8%) for patients with nonmetastatic cancer, and 33.9% (95% CI, 33.3%-34.4%) for patients with metastatic cancer. Compared with nonmetastatic cancer, the age-, sex-, and comorbidity-adjusted relative rate of death was similar for CKD (adjusted relative rate, 1.00; 95% CI, 0.97-1.03; P = .92) during the first year of follow-up and was higher for CKD at years 1 to 5 (adjusted relative rate 1.23; 95% CI, 1.19-1.26). During the first year of follow-up, for patients with CKD, adjusted rates of placement in long-term care (adjusted relative rate, 0.88; 95% CI, 0.82-0.94) and hospitalization (adjusted relative rate, 0.65; 95% CI, 0.64-0.66) were lower than rates for patients with nonmetastatic cancer; however, those rates were higher for the CKD group than for the nonmetastatic cancer group during years 1 to 5 (long-term care placement, adjusted relative rate, 1.36; 95% CI, 1.29-1.43; hospitalization, adjusted relative rate, 1.55; 95% CI, 1.52-1.58). As expected, adjusted rates of long-term care placement and hospitalization were higher for patients with metastatic cancer than for the other 2 groups. Conclusions and Relevance: In this study, mortality, hospitalization, and likelihood of placement into long-term care were similar for CKD and nonmetastatic cancer. These data highlight the importance of CKD as a public health problem.

Prophylactic clipping to prevent delayed colonic post-polypectomy bleeding: meta-analysis of randomized and observational studies.

BACKGROUND AND AIMS: Delayed post-polypectomy bleeding (DPPB) is a commonly described adverse event following polypectomy. Prophylactic clipping may prevent DPPB in some patient subgroups. We performed a meta-analysis to assess both the efficacy and real-world effectiveness of prophylactic clipping. METHODS: We performed a database search through March 2020 for clinical trials or observational studies assessing prophylactic clipping and DPPB. Pooled risk ratios (RR) were calculated using random effects models. Subgroup, sensitivity, and meta-regression analyses were performed to elucidate clinical or methodological factors associated with effects on outcomes. RESULTS: A total of 2771 citations were screened, with 11 randomized controlled trials (RCTs) and 9 observational studies included, representing 24,670 colonoscopies. DPPB occurred in 2.0% of patients overall. The pooled RR of DPPB was 0.47 (95% CI 0.29-0.77) from RCTs enrolling only patients with polyps ≥ 20 mm. Remaining pooled RCT data did not demonstrate a benefit for clipping. The pooled RR of DPPB was 0.96 (95% CI 0.61-1.51) from observational studies including all polyp sizes. For patients with proximal polyps of any size, the RR was 0.73 (95% CI 0.33-1.62) from RCTs. Meta-regression confirmed that polyp size ≥ 20 mm significantly influenced the effect of clipping on DPPB. CONCLUSION: Pooled evidence demonstrates a benefit when clipping polyps measuring ≥ 20 mm, especially in the proximal colon. In lower-risk subgroups, prophylactic clipping likely results in little to no difference in DPPB.

Mortality and cardiovascular events in adults with kidney failure after major non-cardiac surgery: a population-based cohort study.

BACKGROUND: People with kidney failure have a high incidence of major surgery, though the risk of perioperative outcomes at a population-level is unknown. Our objective was to estimate the proportion of people with kidney failure that experience acute myocardial infarction (AMI) or death within 30 days of major non-cardiac surgery, based on surgery type. METHODS: In this retrospective population-based cohort study, we used administrative health data to identify adults from Alberta, Canada with major surgery between April 12,005 and February 282,017 that had preoperative estimated glomerular filtration rates (eGFRs) < 15 mL/min/1.73m2 or received chronic dialysis. The index surgical procedure for each participant was categorized within one of fourteen surgical groupings based on Canadian Classification of Health Interventions (CCI) codes applied to hospitalization administrative datasets. We estimated the proportion of people that had AMI or died within 30 days of the index surgical procedure (with 95% confidence intervals [CIs]) following logistic regression, stratified by surgery type. RESULTS: Overall, 3398 people had a major surgery (1905 hemodialysis; 590 peritoneal dialysis; 903 non-dialysis). Participants were more likely male (61.0%) with a median age of 61.5 years (IQR 50.0-72.7). Within 30 days of surgery, 272 people (8.0%) had an AMI or died. The probability was lowest following ophthalmologic surgery at 1.9% (95%CI: 0.5, 7.3) and kidney transplantation at 2.1% (95%CI: 1.3, 3.2). Several types of surgery were associated with greater than one in ten risk of AMI or death, including retroperitoneal (10.0% [95%CI: 2.5, 32.4]), intra-abdominal (11.7% [8.7, 15.5]), skin and soft tissue (12.1% [7.4, 19.1]), musculoskeletal (MSK) (12.3% [9.9, 15.5]), vascular (12.6% [10.2, 15.4]), anorectal (14.7% [6.3, 30.8]), and neurosurgical procedures (38.1% [20.3, 59.8]). Urgent or emergent procedures had the highest risk, with 12.1% experiencing AMI or death (95%CI: 10.7, 13.6) compared with 2.6% (1.9, 3.5) following elective surgery. CONCLUSIONS: After major non-cardiac surgery, the risk of death or AMI for people with kidney failure varies significantly based on surgery type. This study informs our understanding of surgery type and risk for people with kidney failure. Future research should focus on identifying high risk patients and strategies to reduce these risks.

Derivation and External Validation of a Risk Index for Predicting Acute Kidney Injury Requiring Kidney Replacement Therapy After Noncardiac Surgery.

Importance: Severe acute kidney injury (AKI) is a serious postoperative complication. A tool for predicting the risk of AKI requiring kidney replacement therapy (KRT) after major noncardiac surgery might assist with patient counseling and targeted use of measures to reduce this risk. Objective: To derive and validate a predictive model for AKI requiring KRT after major noncardiac surgery. Design, Setting, and Participants: In this prognostic study, 5 risk prediction models were derived and internally validated in a population-based cohort of adults without preexisting kidney failure who underwent noncardiac surgery in Alberta, Canada, between January 1, 2004, and December 31, 2013. The best performing model and corresponding risk index were externally validated in a population-based cohort of adults without preexisting kidney failure who underwent noncardiac surgery in Ontario, Canada, between January 1, 2007, and December 31, 2017. Data analysis was conducted from September 1, 2019, to May 31, 2021. Exposures: Demographic characteristics, surgery type, laboratory measures, and comorbidities before surgery. Main Outcomes and Measures: Acute kidney injury requiring KRT within 14 days after surgery. Discrimination was assessed using the C statistic; calibration was assessed using calibration intercept and slope. Logistic recalibration was used to optimize model calibration in the external validation cohort. Results: The derivation cohort included 92 114 patients (52.2% female; mean [SD] age, 62.3 [18.0] years), and the external validation cohort included 709 086 patients (50.8% female; mean [SD] age, 61.0 [16.0] years). A total of 529 patients (0.6%) developed postoperative AKI requiring KRT in the derivation cohort, and 2956 (0.4%) developed postoperative AKI requiring KRT in the external validation cohort. The following factors were consistently associated with the risk of AKI requiring KRT: younger age (40-69 years: odds ratio [OR], 2.07 [95% CI, 1.69-2.53]; <40 years: OR, 3.73 [95% CI, 2.61-5.33]), male sex (OR, 1.55; 95% CI, 1.28-1.87), surgery type (colorectal: OR, 4.86 [95% CI, 3.28-7.18]; liver or pancreatic: OR, 6.46 [95% CI, 3.85-10.83]; other abdominal: OR, 2.19 [95% CI, 1.66-2.89]; abdominal aortic aneurysm repair: OR, 19.34 [95% CI, 14.31-26.14]; other vascular: OR, 7.30 [95% CI, 5.48-9.73]; thoracic: OR, 3.41 [95% CI, 2.07-5.59]), lower estimated glomerular filtration rate (OR, 0.97; 95% CI, 0.97-0.97 per 1 mL/min/1.73 m2 increase), lower hemoglobin concentration (OR, 0.99; 95% CI, 0.98-0.99 per 0.1 g/dL increase), albuminuria (mild: OR, 1.88 [95% CI, 1.52-2.33]; heavy: OR, 3.74 [95% CI, 2.98-4.69]), history of myocardial infarction (OR, 1.63; 95% CI, 1.32-2.03), and liver disease (mild: OR, 2.32 [95% CI, 1.66-3.24]; moderate or severe: OR, 4.96 [95% CI, 3.58-6.85]). In external validation, a final model including these variables showed excellent discrimination (C statistic, 0.95; 95% CI, 0.95-0.96), with sensitivity of 21.2%, specificity of 99.9%, positive predictive value of 38.1%, and negative predictive value of 99.7% at a predicted risk threshold of 10% or greater. Conclusions and Relevance: The findings suggest that this risk model can predict AKI requiring KRT after noncardiac surgery using routine preoperative data. The model may be feasible for implementation in clinical perioperative risk stratification for severe AKI.

Angiotensin-Converting Enzyme Inhibitor/Receptor Blocker, Diuretic, or Nonsteroidal Anti-inflammatory Drug Use After Major Surgery and Acute Kidney Injury: A Case-Control Study.

BACKGROUND: Acute kidney injury (AKI) is common after surgery and associated with increased mortality, costs, and lengths of hospitalization. We examined associations between angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), diuretic, or nonsteroidal anti-inflammatory drug (NSAID) use after major surgery and AKI. MATERIALS AND METHODS: We conducted a nested case-control study of patients who underwent major cardiac, thoracic, general, or vascular surgery in Calgary, Alberta, Canada. Cases with AKI were matched on age, gender, and surgery type with up to five controls without AKI within 30-d after surgery. Adjusted odds ratios (ORs) for AKI were determined based on postoperative administration of ACEIs/ARBs, diuretics, or NSAIDs. RESULTS: Among 33,648 patients in the cohort, 2911 cases with AKI were matched to 9309 controls without AKI. Postoperative diuretic [OR = 1.96; 95% confidence interval (CI) = 1.68-2.29], but not ACEI/ARB (OR = 0.83; 95% CI = 0.72-0.95) or NSAID (OR = 1.12; 95% CI = 0.96-1.31), use was independently associated with higher odds of AKI (including stages 1 and 2/3 AKI) after all types of major surgery. There were increased adjusted odds of AKI 1 to 5 d after first exposure to diuretics and 1 d after first exposure to NSAIDs (but not after later exposures). Relationships between ACEI/ARB use and AKI varied by surgery type (p-interaction = 0.004), with lower odds of AKI observed among ACEI/ARB use after cardiac surgery (OR = 0.70; 95% CI = 0.57-0.81), but no difference after other major surgeries. CONCLUSIONS: Postoperative administration of diuretics and NSAIDs was associated with increased odds of AKI after major surgery. These findings characterize potentially modifiable medication exposures associated with AKI after surgery.

New Ileostomy Formation and Subsequent Community-onset Acute and Chronic Kidney Disease: A Population-based Cohort Study.

OBJECTIVE: The aim of this study was to examine relationships between ileostomy formation and subsequent kidney disease. SUMMARY AND BACKGROUND DATA: Colonic absorptive capacity loss from ileostomy formation can cause volume depletion and could result in kidney disease. METHODS: We conducted a population-based cohort study comparing patients who underwent ileostomy formation with or without bowel resection (ileostomy group) to patients who underwent bowel resection without ileostomy formation (reference group). Adjusted odds ratios (aORs) for community-onset acute kidney injury (AKI) within 3 months and new-onset chronic kidney disease (CKD) within 1 year following hospital discharge were determined. RESULTS: Among 19,889 patients, 4136 comprised the ileostomy group and 15,753 comprised the reference group; 1350 patients experienced community-onset AKI and 464 developed new-onset CKD. The aOR for community-onset AKI with ileostomy formation was 4.08 [95% confidence interval (CI) = 3.62-4.61] for any stage AKI, 7.08 (95% CI = 5.66-8.85) for stage ≥2 injury, and 7.67 (95% CI = 5.06-11.63) for stage 3 injuries. Community-onset AKI modified associations between ileostomy formation and new-onset CKD (P = 0.002). Odds of new-onset CKD were increased in the ileostomy group relative to the reference group for patients both with (aOR = 4.99; 95% CI = 3.42-7.28) and without (aOR = 2.45; 95% CI = 1.85-2.23) previous community-onset AKI episodes. In analyses comparing patients that underwent ileostomy formation and subsequent reversal within 1 year to the reference group without ileostomy, the relationship with new-onset CKD was attenuated for patients both with (aOR = 2.49; 95% CI = 1.50-4.12) and without (aOR = 0.97; 95% CI = 0.67-1.40) previous community-onset AKI episodes. CONCLUSIONS: Ileostomy formation is strongly associated with subsequent kidney disease. Vigilance for this complication and new strategies for prevention and treatment are necessary.

Costs and consequences of acute kidney injury after cardiac surgery: A cohort study.

OBJECTIVES: Acute kidney injury (AKI) is common after cardiac surgery. We quantified the mortality and costs of varying degrees of AKI using a population-based cohort in Alberta, Canada. METHODS: A cohort of patients undergoing cardiac surgery from 2004 to 2009 was assembled from linked Alberta administrative databases. AKI was classified by Kidney Disease Improving Global Outcomes stages of severity. Our outcomes were in-hospital mortality, length of stay, and costs; among survivors, we also examined mortality and costs at 365 days. Estimates were adjusted for demographic characteristics, comorbidities, and other covariates. RESULTS: Ten thousand one hundred seventy participants were included, of whom 9771 patients were discharged to community. Overall in-hospital mortality, costs, and length of stay were 4%, 7 days, and Can $34,000, respectively. Postcardiac surgery, AKI occurred in 25%. Compared with those without AKI, AKI was independently associated with increased in-hospital mortality across severity categories, with the highest risk (adjusted odds ratio, 37.1; 95% confidence interval, 26.3-52.1; P < .001) in patients who required acute dialysis. AKI severity was associated with increased hospital days and costs, with costs ranging from 1.21 for stage 1 AKI (95% confidence interval, 1.17-1.23) to 2.74 for acute dialysis (95% confidence interval, 2.49-3.00) (P < .001) times higher than in patients without AKI, after covariate adjustment. Postdischarge to 365 days, patients with AKI continued to experience increased costs up to 1.35-fold, and patients who required dialysis acutely continued to experience a 2.86-fold increased mortality. CONCLUSIONS: AKI remains an important indicator of mortality and health care costs postcardiac surgery.

Nephrology consultation and kidney failure in people with stage 4 chronic kidney disease: a population-based cohort study.

BACKGROUND: Guidelines recommend referral for nephrology consultation for people with severe chronic kidney disease (CKD) to improve care and renal outcomes, yet the advocated benefits of nephrology referral on CKD progression in this patient population are unclear. METHODS: We linked laboratory and administrative data in Alberta, Canada to identify adults with stage 4 CKD between 2002 and 2014 (follow-up end on March 31, 2017). We studied the association between time-varying receipt of outpatient nephrology consultation and kidney failure (the earlier of renal replacement initiation or eGFR < 10 mL/min/1.73 m2 for more than 3 months), accounting for the competing risk of death. RESULTS: Of the 14,382 participants, 41% were ≥ 85 years old, 33% saw a nephrologist as an outpatient, 9% developed kidney failure, and 53% died over a median of 2.6 years. Compared with people who did not see a nephrologist before or at 7 months (median time to consultation), those who did were more likely to develop kidney failure [5-year risk (95% CI) 0.23 (0.21-0.24) vs 0.07 (0.065-0.075)]. With increasing age or higher eGFR, the 5-year risk of kidney failure became progressively smaller, from 0.24 (0.18-0.29) at age < 65 to 0.01 (0.006-0.015) at age ≥ 85 years and from 0.21 (0.18-0.23) at eGFR 15-19 to 0.066 (0.060-0.072) at eGFR 25-29 mL/min/1.73 m2; yet, the hazard ratio of kidney failure (1.6-4.3) increased following nephrology consultation in people who were older or had higher eGFR. CONCLUSIONS: Adults with stage 4 CKD who see a nephrologist are more likely to develop kidney failure than those who don't, especially within lower absolute risk categories. Although selective referral may explain these findings, there is no evidence of an association between nephrology care and reduced risk of kidney failure in people with severe CKD. Studies are needed to assess the benefits of nephrology consultation in people with moderate CKD.