Oral Anticoagulation Use in Individuals With Atrial Fibrillation and Chronic Kidney Disease: A Review.

Atrial fibrillation (AF) is highly prevalent in patients with chronic kidney disease (CKD). It is associated with an increased risk of stroke, which increases as kidney function declines. In the general population and in those with a moderate degree of CKD (creatinine clearance 30-50 mL/min), the use of oral anticoagulation to decrease the risk of stroke has been the standard of care based on a favorable risk-benefit profile that had been established in seminal randomized controlled trials. However, evidence regarding the use of oral anticoagulants for stroke prevention is less clear in patients with severe CKD (creatinine clearance <30 mL/min) and those receiving maintenance dialysis, as these individuals were excluded from such large randomized controlled trials. Nevertheless, the direct oral anticoagulants have invariably usurped vitamin K antagonists as the preferred choice for oral anticoagulation among patients with AF across all strata of CKD based on their well-defined safety and efficacy and multiple pharmacokinetic benefits (e.g., less drug-drug interactions). This review summarizes the current literature on the role of oral anticoagulation in the management of AF among patients with CKD and highlights current deficiencies in the evidence base and how to overcome them.

Periconceptional Serum Creatinine and Risk of Childhood Autism Spectrum Disorder: A Research Letter.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition that manifests in early childhood, in which the maternal metabolic syndrome may be a risk factor. The kidney is a barometer of maternal metabolic syndrome duration and severity. Objective: The main objective of this study is to determine whether periconceptional kidney function is associated with ASD in early childhood. Design Setting and Participants: This retrospective population-based cohort study was completed in Ontario, Canada. Included were singleton children born in an Ontario hospital between April 2007 and March 2021, who were alive at age 48 months and whose mother had a recorded prepregnancy body mass index (BMI) and a measured serum creatinine (SCr) between 120 days preconception and 28 days postconception. Measurement: The main study outcome was a diagnosis of ASD between ages 24 and 48 months. Methods: Relative risks (RRs) of ASD in association with periconceptional SCr were generated using modified Poisson regression and adjusted for several confounders. Results: The cohort comprised 86 054 women, who had 89 677 liveborn children surviving to at least 48 months of age. There was no significant association between periconceptional SCr and ASD (RR: 0.86; 95 % confidence interval: [0.67, 1.10]). Limitations: Selection bias may have arisen had SCr been ordered on clinical grounds. Conclusions: Further study is warranted to determine whether prepregnancy glomerular hyperfiltration is a marker of ASD and other behavioral conditions in childhood. To do so, a more accurate measure of hyperfiltration is needed than SCr.

Contexte: Des problèmes d'innocuité sont détectés dans environ un tiers des médicaments d'ordonnance au cours des années qui suivent leur approbation par l'organisme de réglementation. Les personnes âgées, en particulier celles qui sont atteintes d'insuffisance rénale chronique, sont particulièrement exposées aux effets indésirables des médicaments d'ordonnance. Ce protocole décrit une nouvelle approche qui, à partir des données administratives du système de santé, pourrait permettre d'identifier plus efficacement les signaux crédibles sur la sécurité des médicaments. Objectif: Utiliser l'informatique à haut débit et l'automatisation pour mener plus de 700 études de cohorte sur l'innocuité des médicaments chez les adultes âgés résidant en Ontario (Canada). Chaque étude comparera 74 résultats aigus (30 jours) chez des patients qui commencent un nouveau médicament sur ordonnance (nouveaux utilisateurs) à ceux d'un groupe de non-utilisateurs avec des caractéristiques de santé initiales similaires. Les risques seront évalués par strates de la fonction rénale initiale. Cadre et type d'étude: Études populationnelles de cohortes de nouveaux utilisateurs de médicaments menées à l'aide des bases de données administratives couplées du système de santé ontarien (Canada). Période étudiée: du 1er janvier 2008 au 1er mars 2020. Population source: les Ontariens de 66 ans ou plus ayant rempli au moins une ordonnance pour patient non hospitalisé par l'entremise du Program de médicaments de l'Ontario (PMO) pendant la période de l'étude (tous les résidents de la province bénéficient d'un système de soins de santé universel; les personnes âgées de 65 ans et plus bénéficient d'une couverture universelle des médicaments d'ordonnance par l'intermédiaire du PMO). Sujets: Nous avons identifié 3,2 millions d'adultes âgés dans la population source au cours de la période d'étude et constitué plus de 700 cohortes de médicaments, chacune contenant des groupes mutuellement exclusifs de nouveaux utilisateurs et de non-utilisateurs. Les non-utilisateurs se sont vu attribuer au hasard des dates d'entrée dans la cohorte qui suivaient les dates de début d'ordonnance des nouveaux utilisateurs. Les critères d'admissibilité étaient d'avoir une mesure initiale du débit de filtration glomérulaire estimé [DFGe] dans les 12 mois précédant la date d'entrée dans la cohorte (dans le groupe des nouveaux utilisateurs, le délai médian était de 71 jours avant l'entrée dans la cohorte), ne pas suivre de dialyze chronique, ne pas avoir eu de greffe rénale et n'avoir jamais eu de prescription d'un médicament de la même sous-classe que le médicament à l'étude. Les nouveaux utilisateurs et les non-utilisateurs seront jumelés selon environ 400 caractéristiques de santé initiales à l'aide de la probabilité inverse de traitement pondérée selon les scores de propension dans les trois strates de mesure du DFGe initial: ≥60 ml/min/1,73 m2; 45 à <60 ml/min/1,73 m2 et <45 ml/min/1,73 m2. Résultats: Nous comparerons les groupes de nouveaux utilisateurs et de non-utilisateurs selon 74 critères de jugement cliniquement pertinents (17 critères composites et 57 critères individuels) pendant les 30 jours suivant l'entrée dans la cohorte. Une approche prédéfinie a permis de déterminer ces 74 résultats. Plan d'analyze statistique: Dans chaque cohorte, nous calculerons les différences de risque (par régression de Poisson) et les rapports de risque (par régression binomiale) pondérés pour chaque strate de DFGe. Les interactions additives et multiplicatives par catégorie de DFGe seront examinées. Les associations médicaments-résultats répondant à des critères prédéfinis (signaux identifiés) seront examinées plus avant dans des analyses supplémentaires (survie, exposition à des témoins négatifs, analyses de la valeur E, etc.) et des visualizations. Résultats: Dans les cohortes initiales de médicaments, les médianes sont de 6 120 nouveaux utilisateurs (intervalle interquartile de 1 469 à 38 839) et de 1 088 301 non-utilisateurs (intervalle interquartile de 751 697 à 1 267 009). Les médicaments comptant le plus grand nombre de nouveaux utilisateurs sont le trihydrate d'amoxicilline (n = 1 000 032), la céfalexine (n = 571 566), l'acétaminophène sur ordonnance (n = 571 563) et la ciprofloxacine (n = 504 374). De 19 à 29 % des nouveaux utilisateurs dans ces cohortes présentaient un DFGe < 60 ml/min/1,73 m2. Limites: Malgré l'utilization de techniques robustes pour équilibrer les indicateurs de base et pour contrôler le risque de confusion par indication, il pourrait subsister des facteurs de confusion résiduels. Seuls les résultats aigus (30 jours) seront examinés. Nos sources de données ne comprennent pas les médicaments sans ordonnance (en vente libre) ni les médicaments prescrits dans les hôpitaux, et n'incluent pas l'utilization de médicaments sur ordonnance en ambulatoire chez les enfants ou les adultes de moins de 65 ans. Conclusion: Cette approche accélérée pour la réalisation d'études d'innocuité des médicaments après leur mise en marché a le potentiel de détecter efficacement les effets indésirables de ces médicaments dans une population vulnérable. Les résultats de ce protocole serviront à améliorer l'innocuité des médicaments.

Preconception SGLT2 or DPP4 inhibitor use and adverse pregnancy outcomes.

AIMS: To compare preconception use of sodium-glucose cotransporter-2 (SGLT2i) and dipeptidyl peptidase-4 (DPP4i) inhibitors to sulfonylurea agents, and associated peri-conceptional A1c concentration, and risk of pregnancy loss and congenital anomalies. METHODS: This population-based cohort study used administrative datasets for all of Ontario, Canada, and included women eligible for free medication coverage and who achieved a recognized pregnancy from April 2007-November 2021. Exposure was a SGLT2i, DPP4i or sulfonylurea (referent) dispensed at least 90 days preconception. Study outcomes included differences in periconceptional A1c; miscarriage, induced abortion, or stillbirth; and any congenital anomaly - the latter two outcomes assessed using propensity score overlap weighting. RESULTS: The mean (SD) periconceptional A1c was 8.1 % (2.0) among those prescribed any sulfonylurea, compared with 8.3 % (2.0) with a DPP4i and 7.8 % (1.6) with any SGLT2i. The risk of pregnancy loss was lowest among those exclusively prescribed a SGLT2i (relative risk [RR] 0.51, 95 % CI 0.22 to 0.91). Risk of a congenital anomaly at birth did not differ significantly comparing DPP4i or SGLT2i to sulfonylurea agents. CONCLUSIONS: Neither SGLT2i nor DPP4i use before pregnancy was associated with a difference in A1c, or a higher risk of selective adverse outcomes, compared to sulfonylureas. Future larger studies are required, including assessment of medication use after conception, during the critical period of embryogenesis.

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.

Association of Primary Versus Rotating Nephrologist Model of Care in Hemodialysis Programs with Patient Outcomes.

SIGNIFICANCE STATEMENT: Nephrologist staffing models for patients receiving hemodialysis vary widely. Patients may be cared for continuously by a single primary nephrologist or by a group of nephrologists on a rotating basis. It remains unclear whether these differing care models influence clinical outcomes. In this population-based cohort study of more than 14,000 incident patients on maintenance hemodialysis from Ontario, Canada, we found no difference in mortality, kidney transplantation, home dialysis initiation, hospitalizations, or emergency department visits when care was provided by a single primary nephrologist or a rotating group of nephrologists. These results suggest that primary nephrologist models do not necessarily improve objective clinical outcomes, providing reassurance to patients, providers, and administrators that both models are acceptable options.

Pre-Pregnancy eGFR and the Risk of Adverse Maternal and Fetal Outcomes: A Population-Based Study.

SIGNIFICANCE STATEMENT: Pregnancies in women with CKD carry greater risk than pregnancies in the general population. The small number of women in prior studies has limited estimates of this risk, especially among those with advanced CKD. We report the results of a population-based cohort study in Ontario, Canada, that assessed more than 500,000 pregnancies, including 600 with a baseline eGFR < 60 ml/min per 1.73 m 2 . The investigation demonstrates increases in risk of different adverse maternal and fetal outcomes with lower eGFR and further risk elevation with baseline proteinuria. BACKGROUND: CKD is a risk factor for pregnancy complications, but estimates for adverse outcomes come largely from single-center studies with few women with moderate or advanced stage CKD. METHODS: To investigate the association between maternal baseline eGFR and risk of adverse pregnancy outcomes, we conducted a retrospective, population-based cohort study of women (not on dialysis or having had a kidney transplant) in Ontario, Canada, who delivered between 2007 and 2019. The study included 565,907 pregnancies among 462,053 women. Administrative health databases captured hospital births, outpatient laboratory testing, and pregnancy complications. We analyzed pregnancies with serum creatinine measured within 2 years of conception up to 30 days after conception and assessed the impact of urine protein where available. RESULTS: The risk of major maternal morbidity, preterm delivery, and low birthweight increased monotonically across declining eGFR categories, with risk increase most notable as eGFR dropped below 60 ml/min per 1.73 m 2 . A total of 56 (40%) of the 133 pregnancies with an eGFR <45 ml/min per 1.73 m 2 resulted in delivery under 37 weeks, compared with 10% of pregnancies when eGFR exceeded 90 ml/min per 1.73 m 2 . Greater proteinuria significantly increased risk within each eGFR category. Maternal and neonatal deaths were rare regardless of baseline eGFR (<0.3% of all pregnancies). Only 7% of women with an eGFR <45 ml/min per 1.73 m 2 received dialysis during or immediately after pregnancy. CONCLUSIONS: We observed higher rates of adverse pregnancy outcomes in women with low eGFR with concurrent proteinuria. These results can help inform health care policy, preconception counseling, and pregnancy follow-up in women with CKD.

Cardiovascular Drug Use After Acute Kidney Injury Among Hospitalized Patients With a History of Myocardial Infarction.

Introduction: Patients who survive acute kidney injury (AKI) may receive fewer cardioprotective drugs. Our objective was to measure the difference in time to dispensing of evidence-based cardiovascular drugs in patients with a history of myocardial infarction (MI) with and without AKI. Methods: This was a population-based cohort study of patients 66 years of age and older with a history of MI who survived a hospitalization complicated with AKI, propensity-score matched to patients without AKI. The primary outcome was time to outpatient dispensing of an angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB), statin, or ß-blocker within 1 year of hospital discharge. Results: We identified 28,871 patients with AKI, of whom 21,452 were matched 1:1 to patients without AKI. In the matched cohort, mean age was 80 years, 40% were female, and 34% had an MI during the index hospitalization. AKI was associated with less frequent dispensing of all 3 cardiovascular drug classes within 1 year of hospital discharge (subdistribution hazard ratio [sHR], 0.93; 95% confidence interval [CI], 0.91-0.95). This association was most pronounced in patients with stage 2 (sHR, 0.81; 95% CI, 0.75-0.88) and stage 3 (sHR, 0.71; 95% CI, 0.64-0.79) AKI. We observed less frequent dispensing of statins in patients with stage 2 (sHR, 0.87; 95% CI, 0.81-0.92) and stage 3 (sHR, 0.85; 95% CI, 0.78-0.93) AKI and less frequent dispensing of ß-blockers in patients with stage 3 AKI (sHR, 0.86; 95% CI, 0.79-0.94). Conclusion: In patients with a history of MI, survivors of AKI were less likely to receive prescriptions for ACEi/ARB, statins, or ß-blockers within 1 year of hospital discharge. This association was most pronounced in patients with stages 2 and 3 AKI.

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.

Association of an Acute Kidney Injury Follow-up Clinic With Patient Outcomes and Care Processes: A Cohort Study.

RATIONALE & OBJECTIVE: To determine whether attendance at an acute kidney injury (AKI) follow-up clinic is associated with reduced major adverse kidney events. STUDY DESIGN: Propensity-matched cohort study. SETTING & PARTICIPANTS: Patients hospitalized with AKI in Ontario, Canada, from February 1, 2013, through September 30, 2017, at a single clinical center, who were not receiving dialysis when discharged. EXPOSURE: Standardized assessment by a nephrologist. OUTCOMES: Time to a major adverse kidney event, defined as death, initiation of maintenance dialysis, or incident/progressive chronic kidney disease. ANALYTICAL APPROACH: Propensity scores were used to match each patient who attended an AKI follow-up clinic to 4 patients who received standard care. Cox proportional hazards models were fit to assess the association between the care within an AKI follow-up clinic and outcomes. To avoid immortal time bias, we randomly assigned index dates to the comparator group. RESULTS: We matched 164 patients from the AKI follow-up clinic to 656 patients who received standard care. During a mean follow-up of 2.2±1.3 (SD) years, care in the AKI follow-up clinic was not associated with a reduction in major adverse kidney events relative to standard care (22.1 vs 24.7 events per 100 patient-years; HR, 0.91 [95% CI, 0.75-1.11]). The AKI follow-up clinic was associated with a lower risk of all-cause mortality (HR, 0.71 [95% CI, 0.55-0.91]). Patients aged at least 66 years who attended the AKI follow-up clinic were more likely to receive ß-blockers (HR, 1.34 [95% CI, 1.02-1.77]) and statins (HR, 1.35 [95% CI, 1.05-1.74]), but not angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (HR, 1.21 [95% CI, 0.94-1.56]). LIMITATIONS: Single-center study and residual confounding. CONCLUSIONS: Specialized postdischarge follow-up for AKI survivors was not associated with a lower risk of major adverse kidney events but was associated with a lower risk of death and increased prescriptions for some cardioprotective medications.

Peritoneal Fluid Analysis in Peritoneal Dialysis-Associated Peritonitis.

A 62-year-old woman undergoing peritoneal dialysis (PD) presented to the clinic with severe abdominal pain and cloudy PD fluid. Seven days prior, she inadvertently broke aseptic technique when tightening a leaking connection of her PD catheter tubing. Cloudy fluid that was drained from her PD catheter was sent for laboratory analysis. What would you do next?

Use of Guideline-Based Therapy for Diabetes, Coronary Artery Disease, and Chronic Kidney Disease After Acute Kidney Injury: A Retrospective Observational Study.

Background: Survivors of acute kidney injury (AKI) are at a high risk for cardiovascular complications. An underrecognition of this risk may contribute to the low utilization of relevant guideline-based therapies in this population. Objective: We sought to assess accordance with guideline-based recommendations for survivors of AKI with diabetes, coronary artery disease (CAD), and preexisting chronic kidney disease (CKD) in a post-AKI clinic, and identify factors that may be associated with guideline accordance. Design: Retrospective cohort study. Setting: Post-AKI clinics at 2 tertiary care centers in Ontario, Canada. Patients: We included adult patients seen in both post-AKI clinics between 2013 and 2019 who had at least 2 clinic visits within 24 months of an index AKI hospitalization. Measurements: We assessed accordance to recommendations from the most recent North American and international guidelines available at the time of study completion for diabetes, CAD, and CKD. Methods: We compared guideline accordance between visits using the Cochran Mantel Haenszel test. We used multivariable Poisson regression to identify prespecified factors associated with accordance. Results: Of 213 eligible patients, 192 (90%) had Kidney Disease Improving Global Outcomes Stage 2-3 AKI, 91 (43%) had diabetes, 76 (36%) had CAD, and 88 (41%) had preexisting CKD. From the first clinic visit to the second, there was an increase in angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACE-I/ARB) use across all disease groups-from 33% to 46% (P = .028) in patients with diabetes, from 30% to 57% (P = .002) in patients with CAD, and from 16% to 35% (P < .001) in patients with preexisting CKD. Statin use increased in patients with preexisting CKD from 64% to 71% (P = .034). Every 25 µmol/L rise in the discharge serum creatinine was associated with a 19% (95% confidence interval [CI], 8%-28%) and 12% (95% CI, 2%-21%) lower likelihood of being on an ACE-I/ARB in patients with diabetes and preexisting CKD, respectively. Limitations: The study lacked a comparison group that received usual care. The small sample and multiple comparisons make false positives possible. Conclusion: There is room to improve guideline-based cardiovascular risk factor management in survivors of AKI, particularly ACE-I/ARB use in patients with an elevated discharge serum creatinine.

Contexte: Les survivants d'un épisode d'insuffisance rénale aiguë (IRA) courent un risque élevé de subir des complications cardiovasculaires. Une sous-reconnaissance de ce risque pourrait contribuer à la faible utilisation des thérapies pertinentes recommandées par les lignes directrices dans cette population. Objectif: Évaluer la conformité aux recommandations des lignes directrices pour les survivants d'un épisode d'IRA souffrant de diabète, de maladie coronarienne et d'insuffisance rénale chronique (IRC) préexistante dans une clinique post-IRA, et identifier les facteurs pouvant être associés à la conformité aux recommandations. Conception: Étude de cohorte rétrospective. Cadre: Les cliniques post-IRA de deux centres de soins tertiaires de l'Ontario (Canada). Patients: Nous avons inclus les patients adultes suivis dans les deux cliniques post-IRA entre 2013 et 2019 et ayant visité la clinique au moins deux fois dans les 24 mois suivant une hospitalisation pour IRA. Mesures: Nous avons évalué la conformité aux recommandations des plus récentes lignes directrices nord-américaines et internationales disponibles pour le diabète, la maladie coronarienne et l'IRC au terme de l'étude. Méthodologie: Nous avons comparé la conformité aux recommandations entre les visites à l'aide du test Cochran Mantel Haenszel. La régression multivariée de Poisson a servi à établir les facteurs préspécifiés associés à la conformité. Résultats: Sur les 213 patients admissibles, 192 (90 %) présentaient une IRA de stade KDIGO 2-3, 91 (43 %) étaient diabétiques, 76 (36 %) présentaient une maladie coronarienne et 88 (41 %) une IRC préexistante. Entre la première et la deuxième visite à la clinique, l'utilisation des inhibiteurs de l'enzyme de conversion de l'angiotensine/antagonistes des récepteurs de l'angiotensine (IECA/ARA) a augmenté dans tous les groupes, soit de 33 à 46 % (p = 0,028) chez les diabétiques, de 30 à 57 % (p = 0,002) chez les patients souffrant de maladie coronarienne et de 16 à 35 % (p < 0,001) chez ceux qui avaient une IRC préexistante. L'utilisation des statines est passée de 64 à 71 % (p = 0,034) chez les patients avec une IRC préexistante. Chaque augmentation de 25 µmol/L de la créatinine sérique à la sortie de l'hôpital a été associée, chez les diabétiques et les patients avec une IRC préexistante, à une diminution de la probabilité d'être sous IEAC/ARA de 19 % (IC 95 %: 8-28 %) de 12 % (IC 95 %: 2-21 %) respectivement. Limites: L'étude ne comportait pas de groupe témoin recevant les soins habituels. Le faible échantillon et les multiples comparaisons rendent possibles les faux positifs. Conclusion: Il est possible d'améliorer la prise en charge fondée sur les lignes directrices des facteurs de risques cardiovasculaires chez les survivants d'un épisode d'IRA; particulièrement l'utilisation des IECA/ARA chez les patients dont la mesure de créatinine sérique est élevée à la sortie de l'hôpital.

Amiodarone, Verapamil, or Diltiazem Use With Direct Oral Anticoagulants and the Risk of Hemorrhage in Older Adults.

Background: Routinely used cardiac medications, based on pharmacokinetics, are hypothesized to increase drug levels of direct oral anticoagulants (DOACs), with the potential to increase the risk of hemorrhage. We set out to compare the risk for hemorrhage following initiation of amiodarone, verapamil, or diltiazem (moderate cytochrome P450 3A4 and/or P-glycoprotein activity) vs metoprolol or amlodipine (weak or no activity), among older adults prescribed DOACs. Methods: We conducted a population-based, retrospective cohort study of all adults (aged ≥ 66 years) on a DOAC (dabigatran, apixaban, rivaroxaban; n = 295,038) who were newly prescribed amiodarone (n = 4872), verapamil (n = 1284), or diltiazem (n = 14,638), compared with metoprolol or amlodipine, from Ontario, Canada (2009-2016). The outcome was hospital admission or emergency room visit with a major hemorrhage (upper or lower gastrointestinal tract, intracranial), examined using weighted models. Results: A total of 1737 hemorrhage events occurred (amiodarone, 80 [1.6%] vs metoprolol 503 [2.3%]; verapamil, 32 [2.5%] vs amlodipine, 406 [1.6%]; diltiazem, 312 [2.1%] vs amlodipine, 404 [1.5%]). The weighted risk of major hemorrhage was not elevated with amiodarone, verapamil, or diltiazem initiation in DOAC users, compared to metoprolol or amlodipine, during the full follow-up period (hazard ratio [HR; 95% confidence interval]: amiodarone HR 0.77 [0.61-0.97]; verapamil HR 1.32 [0.88-1.98]; diltiazem HR 0.99 [0.85-1.15]). This finding was consistent with a broader definition of bleeding, adjusting for kidney function, by DOAC type or dosage. Conclusions: Hemorrhage risk with amiodarone, verapamil, and diltiazem was similar to that with comparators, among DOAC users aged > 66 years.

Contexte: Les médicaments cardiaques couramment utilisés, selon la pharmacocinétique, devraient théoriquement augmenter les taux d'anticoagulants oraux directs (AOD), ce qui s'accompagne d'un risque accru d'hémorragie. Nous avons entrepris de comparer le risque d'hémorragie après l'instauration de l'amiodarone, du vérapamil ou du diltiazem (activité modérée du cytochrome P450 3A4 ou de la P-glycoprotéine) par rapport au métoprolol ou à l'amlodipine (activité faible ou nulle), chez des personnes âgées à qui l'on avait prescrit des AOD. Méthodologie: Nous avons mené une étude de cohortes rétrospective en population auprès de tous les adultes (âgés de 66 ans et plus) prenant un AOD (dabigatran, apixaban, rivaroxaban; n = 295 038) à qui l'on venait de prescrire de l'amiodarone (n = 4872), du vérapamil (n = 1284) ou du diltiazem (n = 14 638), comparativement au métoprolol ou à l'amlodipine, en Ontario, au Canada (2009-2016). Le critère d'évaluation était une admission à l'hôpital ou une consultation à l'urgence pour une hémorragie grave (voie gastro-intestinale supérieure ou inférieure, intracrânienne), examiné à l'aide de mo-dèles pondérés. Résultats: Au total, 1 737 événements hémorragiques sont survenus (amiodarone, 80 [1,6 %] contre métoprolol, 503 [2,3 %]; vérapamil, 32 [2,5 %] contre amlodipine, 406 [1,6 %]; diltiazem, 312 [2,1 %] contre amlodipine, 404 [1,5 %]). Le risque pondéré d'hémorragie grave ne s'est pas accru avec l'instauration de l'amiodarone, du vérapamil ou du diltiazem chez les utilisateurs d'AOD, comparativement au métoprolol ou à l'amlodipine, pendant toute la période de suivi (rapport des risques instantanés [RRI; intervalle de confiance à 95 %] : amiodarone : RRI 0,77 [0,61-0,97]; vérapamil : RRI 1,32 [0,88-1,98]; diltiazem : RRI 0,99 [0,85-1,15]). Ce résultat concorde avec une définition plus large du saignement, après ajustement pour la fonction rénale, par type ou posologie d'AOD. Conclusions: Le risque d'hémorragie associé à l'amiodarone, au vérapamil et au diltiazem était semblable à celui des médicaments de comparaison chez les utilisateurs d'AOD âgés de plus de 66 ans.

Risk of Acute Kidney Injury After Hypertensive Disorders of Pregnancy: A Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Even though studies have demonstrated a relationship between hypertensive disorders of pregnancy (HDPs) and chronic kidney disease, there are limited data on the risk of acute kidney injury (AKI) following HDPs. We examined the risk of AKI following the occurrence of HDPs. STUDY DESIGN: Retrospective population-based cohort study. SETTING & PARTICIPANTS: Pregnant women in Ontario, Canada, aged 14-50 years, who delivered at ≥20 weeks' gestation between April 1, 2002, and March 31, 2015. EXPOSURE: Preeclampsia, gestational hypertension, or neither. OUTCOMES: The primary outcome was AKI with receipt of dialysis (AKI-D) ≥90 days after delivery. The main secondary outcome was AKI based on a hospitalization with a diagnostic code for AKI ≥90 days after delivery. ANALYTICAL APPROACH: Time-dependent Cox proportional and cause-specific hazards models were used to evaluate the relationship between HDP and outcomes of interest. Models were adjusted for baseline and time-varying covariates. RESULTS: Our cohort comprised 1,142,656 women and 1,826,235 deliveries, of which 1.7% were associated with gestational hypertension and 4.4% with preeclampsia. After a mean follow-up of 6.7 years, there were 322 episodes of AKI-D (0.41 per 10,000 person-years) and 1,598 episodes of AKI based on diagnostic codes (2.04 per 10,000 person-years). After adjustment, neither preeclampsia nor gestational hypertension was associated with AKI-D. Preeclampsia was associated with AKI (HR, 1.22 [95% CI, 1.03-1.45]), but gestational hypertension was not. LIMITATIONS: Retrospective design and possible unmeasured confounding. Cases of HDPs and AKI may have been undetected. CONCLUSIONS: Preeclampsia was a risk factor for AKI occurring ≥90 days after delivery. Our findings suggest the potential importance of obtaining a pregnancy history as part of a comprehensive risk profile for acute kidney disease and suggest that women with a history of HDP may benefit from monitoring of kidney function.

Association Between Blunted Glomerular Hyperfiltration in Pregnancy and Severe Maternal Morbidity-A Research Letter.

BACKGROUND: Glomerular hyperfiltration is one physiological adaptation to pregnancy, marked by a decline in serum creatinine (SCr) concentration by 16 weeks' gestation. It is not known whether blunted glomerular hyperfiltration leads to adverse maternal outcomes, including severe maternal morbidity (SMM). OBJECTIVE: To evaluate the association between blunted glomerular hyperfiltration and subsequent SMM or death. DESIGN: Population-based cohort study. SETTING: Ontario, Canada, from 2008 to 2019. PARTICIPANTS: Included were births among women who had ≥ 1 SCr measured as an outpatient within 10 weeks before conception ("preconception"), and again, at 110/7 to 206/7 weeks' gestation ("in-pregnancy"). Excluded were women who died before birth, who had end-stage renal disease or kidney transplantation before conception, or whose pre-pregnancy SCr was 125 µmol/L. EXPOSURE: Net glomerular hyperfiltration defined as the preconception minus the in-pregnancy SCr. MEASURES: The primary study outcome was SMM or death arising from 23 weeks' gestation up to 42 days after the index birth. METHODS: Adjusted relative risks (aRRs) were calculated using Modified Poisson regression per 1-SD net blunting of glomerular hyperfiltration adjusting for important covariates. RESULTS: A total of 10,323 births met all inclusion criteria. The mean (SD) SCr was 61.7 (11.0) µmol/L preconception, 48.0 (9.2) µmol/L in-pregnancy, and the mean net difference 13.6 (8.2) µmol/L. Among these births, the adjusted RR of SMM or death from 23 weeks' gestation up to 42 days post-partum was 1.16 (95% confidence interval 1.14-1.30) per 1-SD (8.2 µmol/L) net blunting of glomerular hyperfiltration. LIMITATIONS: As SCr assessment is not a routine part of pregnancy care, its measurement could have been for a specific health condition thereby imparting selection bias. CONCLUSIONS: Blunted glomerular hyperfiltration in pregnancy may identify some women at higher risk of SMM. Further prospective research is needed about the implications of glomerular hyperfiltration in early pregnancy.

CONTEXTE: L'hyperfiltration glomérulaire est une adaptation physiologique à la grossesse qui se caractérise par une baisse du taux de créatinine sérique (CrS) à 16 semaines de gestation. On ignore toutefois si l'hyperfiltration glomérulaire atténuée entraîne des résultats indésirables pour la mère, notamment des cas graves de morbidité maternelle (morbidité maternelle grave­MMG). OBJECTIF: Examiner le lien entre l'hyperfiltration glomérulaire atténuée et une MMG subséquente ou le décès. TYPE D'ÉTUDE: Étude de cohorte basée sur une population. CADRE: Étude menée en Ontario (Canada) entre 2008 et 2019. SUJETS: Ont été retenues pour l'étude les naissances liées à des femmes qui disposaient d'au moins une mesure de la CrS en consultation externe dans les 10 semaines précédant la conception (« préconception ¼) et d'une autre entre les semaines 110/7 et 206/7 de la grossesse (« pendant la grossesse ¼). Ont été exclues les femmes décédées avant l'accouchement, celles qui étaient atteintes d'insuffisance rénale terminale ou qui avaient subi une transplantation rénale avant la conception, ainsi que celles qui présentaient une mesure de la créatinine sérique supérieure à 125 µmol/L avant la grossesse. EXPOSITION: La valeur de l'hyperfiltration glomérulaire nette a été définie comme la différence entre la mesure de CrS préconception et celle mesurée pendant la grossesse. MESURES: Le principal critère d'évaluation était une MMG ou le décès dans la période couvrant de la 23e semaine de grossesse jusqu'à 42 jours après l'accouchement. MÉTHODOLOGIE: Les risques relatifs corrigés (RRc) ont été calculés à l'aide d'un modèle de régression de Poisson modifié pour 1-ÉT pour l'hyperfiltration glomérulaire atténuée corrigée en tenant compte des covariables importantes. RÉSULTATS: Au total, 10 323 naissances répondaient à tous les critères d'inclusion. Le taux de créatinine sérique moyen (ÉT) était de 61,7 (11,0) µmol/L préconception et de 48,0 (9,2) µmol/L pendant la grossesse. La différence nette moyenne s'établissait à 13,6 (8,2) µmol/L. Le RRc de MMG ou de décès pendant la période couvrant de la 23e semaine de grossesse jusqu'à 42 jours après l'accouchement s'établissait à 1,16 (IC 95 %: 1,14-1,30) pour 1-ÉT (8,2 µmol/L) d'hyperfiltration glomérulaire atténuée. LIMITES: La mesure de la CrS n'étant pas une composante courante des soins liés au suivi d'une grossesse, les mesures disponibles pourraient avoir été faites dans un cadre spécifique, ce qui entraîne un biais de sélection. CONCLUSION: L'hyperfiltration glomérulaire atténuée pendant la grossesse pourrait permettre de détecter les femmes qui présentent un risque accru de MMG. D'autres recherches prospectives portant sur les conséquences de l'hyperfiltration glomérulaire au début de la grossesse sont nécessaires.

Proteinuria and venous thromboembolism in pregnancy: a population-based cohort study.

BACKGROUND: Pregnancy-associated venous thromboembolism (VTE) is associated with high morbidity and mortality. Identification of risk factors of VTE may lead to improved maternal and foetal outcomes. Proteinuria confers a pro-thrombotic state, however, its association with VTE in pregnancy remains unknown. We set out to assess the association of proteinuria and VTE during pregnancy. METHODS: We conducted a population-based, retrospective cohort study of all pregnant women (≥16 years of age) with a proteinuria measure within 20 weeks of conception (n = 306 244; mean age 29.8 years) from Ontario, Canada. Proteinuria was defined by any of the following: urine albumin:creatinine ratio ≥3 mg/mmol, urine protein:creatinine ratio ≥5 mg/mmol or urine dipstick proteinuria ≥1. The main outcome measure was a diagnosis of VTE up to 24-weeks post-partum. RESULTS: A positive proteinuria measurement occurred in 8508 (2.78%) women and was more common with a history of kidney disease, gestational or non-gestational diabetes mellitus and hypertension. VTE events occurred in 625 (0.20%) individuals, with a higher risk among women with positive proteinuria [32 events (0.38%)] compared with women without proteinuria [593 events (0.20%); inverse probability-weighted risk ratio 1.79 (95% confidence interval 1.25-2.57)]. The association was consistent using a more specific VTE definition, in the post-partum period, in high-risk subgroups (hypertension or diabetes) and when the sample was restricted to women with preserved kidney function. CONCLUSIONS: The presence of proteinuria in the first 20 weeks of pregnancy is associated with a significantly higher risk of VTE.

The Risk of Acute Kidney Injury with Oral Anticoagulants in Elderly Adults with Atrial Fibrillation.

BACKGROUND AND OBJECTIVES: Anticoagulation with either a vitamin K antagonist or a direct oral anticoagulant may be associated with AKI. Our objective was to assess the risk of AKI among elderly individuals with atrial fibrillation newly prescribed a direct oral anticoagulant (dabigatran, rivaroxaban, or apixaban) versus warfarin. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our population-based cohort study included 20,683 outpatients in Ontario, Canada, ≥66 years with atrial fibrillation who were prescribed warfarin, dabigatran, rivaroxaban, or apixaban between 2009 and 2017. Inverse probability of treatment weighting on the basis of derived propensity scores for the treatment with each direct oral anticoagulant was used to balance baseline characteristics among patients receiving each of the three direct oral anticoagulants compared with warfarin. Cox proportional hazards regression was performed in the weighted population to compare the association between the prescribed anticoagulant and the outcomes of interest. The exposure was an outpatient prescription of warfarin or one of the direct oral anticoagulants. The primary outcome was a hospital encounter with AKI, defined using Kidney Disease Improving Global Outcomes thresholds. Prespecified subgroup analyses were conducted by eGFR category and by the percentage of international normalized ratio measurements in range, a validated marker of anticoagulation control. RESULTS: Each direct oral anticoagulant was associated with a significantly lower risk of AKI compared with warfarin (weighted hazard ratio, 0.65; 95% confidence interval, 0.53 to 0.80 for dabigatran; weighted hazard ratio, 0.85; 95% confidence interval, 0.73 to 0.98 for rivaroxaban; and weighted hazard ratio, 0.81; 95% confidence interval, 0.72 to 0.93 for apixaban). In the subgroup analysis, the lower risk of AKI associated with each direct oral anticoagulant was consistent across each eGFR strata. The risk of AKI was significantly lower among users of each of the direct oral anticoagulants compared with warfarin users who had a percentage of international normalized ratio measurements ≤56%. CONCLUSIONS: Direct oral anticoagulants were associated with a lower risk of AKI compared with warfarin.