Risk of Relapse of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in a Randomized Controlled Trial of Plasma Exchange and Glucocorticoids.

OBJECTIVE: Relapses of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are important events that can cause organ dysfunction and reduce quality of life. Understanding the effects of the initial treatments for ANCA-associated vasculitis on the subsequent risk of relapse may help guide monitoring and treatment. METHODS: We performed a post hoc analysis of participants with severe ANCA-associated vasculitis enrolled in an international two-by-two factorial randomized controlled trial comparing the effects of plasma exchange (PLEX) to no PLEX and a regimen of reduced glucocorticoid exposure to a standard regimen. We estimated the effects of treatments on relapses of any severity using three competing risk time-to-event models adjusted for patient and disease characteristics and other treatments. Each model was adjusted for disease manifestations in different ways. RESULTS: Of 704 participants, 649 (92.2%) achieved remission and 147 (22.7%) experienced 204 relapses. The relapse rate was 10.3 (95% confidence interval [CI] 8.4-12.1) relapses per 100 patient-years. Neither the use of PLEX (subhazard ratio 0.91-0.94; 95% CIs range from 0.66 to 1.31) nor a glucocorticoid regimen (subhazard ratio 0.93-0.94; 95% CIs range from 0.67 to 1.35) appreciably changed the risk of relapse. Proteinase 3-ANCA and the presence of nonhemorrhagic respiratory manifestations of the disease at trial entry were associated with increased risks of relapse. Receiving dialysis at baseline and administration of oral cyclophosphamide as induction therapy were associated with lower risks of relapse. CONCLUSION: In patients with severe ANCA-associated vasculitis, relapses remain common; neither the use of PLEX nor an initial glucocorticoid tapering regimen impacted relapse risk.

Prospective Study of Ultrasound Markers of Organ Congestion in Critically Ill Patients With Acute Kidney Injury.

Introduction: Organ congestion may be a mediator of adverse outcomes in critically ill patients with severe acute kidney injury (AKI). The presence of abnormal venous Doppler waveforms could identify patients with clinically significant organ congestion who may benefit from a decongestive strategy. Methods: This prospective multicenter cohort study enrolled patients with severe AKI defined as Kidney Disease: Improving Global Outcomes stage 2 or higher. Patients were not eligible if they received renal replacement therapy (RRT) for more than 72 hours at the time of screening. Participants underwent serial Doppler ultrasound examinations of the portal, hepatic and intrarenal veins during the week following enrolment. We calculated the venous excess ultrasound (VExUS) score based on these data. The primary outcome studied was major adverse kidney events at 30 days (MAKE30) defined as death, RRT dependence, or a persistent decrease in kidney function. Results: A total of 125 patients were included for whom 291 ultrasound assessments were performed. Severely abnormal venous waveforms were documented in 14.4% of portal vein assessments, 6.5% of intrarenal venous assessments, and 14.4% of hepatic vein assessments. The individual ultrasound markers were not associated with MAKE30. The VExUS score (grade 0-1: reference; grade 2: adjusted hazard ratio [aHR]: 4.03, confidence interval [CI]: 1.81-8.99; grade 3: aHR: 2.70, CI: 1.10-6.65; P = 0.03), as well as severely abnormal portal, hepatic and intrarenal vein Doppler were each independently associated with mortality. Conclusion: Although not significantly associated with MAKE30, venous Doppler abnormalities suggestive of venous congestion were associated with higher mortality in critically ill patients with severe AKI.

Hierarchical endpoints in critical care: A post-hoc exploratory analysis of the standard versus accelerated initiation of renal-replacement therapy in acute kidney injury and the intensity of continuous renal-replacement therapy in critically ill patients trials.

PURPOSE: To perform a post-hoc reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) and the Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients (RENAL) trials through hierarchical composite endpoint analysis using win ratio (WR). MATERIAL AND METHODS: All patients with complete information from the STARRT-AKI (which compared accelerated versus standard approaches for renal replacement therapy - RRT initiation) and RENAL (which compared two different RRT doses in critically ill patients) trials were selected. WR was defined as a hierarchical composite endpoint using 90-day mortality, RRT dependency at 90-days, intensive care unit (ICU) length-of-stay (LOS), and hospital LOS (primary analysis); values above the unit represent a benefit of the intervention for the hierarchical composite endpoint. A secondary analysis replacing LOS by days alive and free of RRT was performed. Stratified analyses were performed according to illness severity score, surgical status, and the presence of sepsis. RESULTS: The WR analysis produced 2,141,830 pairs for the STARRT-AKI trial and 536,446 pairs for the RENAL trial, respectively. The WR results for STARRT-AKI and RENAL were 1.04 (95% confidence interval [CI] 0.96-1.13; p = 0.33) and 1.02 (95% CI; 0.90-1.15; p = 0.75) for the primary analysis, and 0.88 (95% CI; 0.79-0.99; p = 0.03) and 1.02 (95% CI; 0.87-1.21; p = 0.77) for the secondary analysis, respectively. The stratified analysis of the primary suggested possible benefit of the accelerated-strategy in the STARRT-AKI trial for non-surgical patients with sepsis, while the secondary analysis suggested possible harm of the accelerated-strategy for surgical patients without sepsis. There was no evidence of heterogeneity in treatment effects in stratified analyses in the RENAL trial. CONCLUSION: WR approach using a hierarchical composite endpoint is feasible for trials in critical care nephrology. The primary re-analyses of the STARRT-AKI and RENAL trials both yielded neutral results; however, there was suggestion of heterogeneity in treatment effect in stratified analyses of the STARRT-AKI trial by surgical status and sepsis. Selection of the endpoints and hierarchical ordering before trial design using the WR approach can have important implications for trial interpretation. TRIAL REGISTRY: ClinicalTrials.gov number NCT02568722 (STARRT-AKI) and NCT00076219 (RENAL).

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis.

OBJECTIVES: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. DESIGN: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722). SETTING: One hundred-fifty-three ICUs in 13 countries. PATIENTS: Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ (p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ (p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU (p < 0.001) and hospital discharge (p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], -11.3%; 95% CI, -17.7% to -4.8%; p < 0.001 and for ANZ vs. North America: RD, -10.3%; 95% CI, -17.5% to -3.1%; p = 0.007). CONCLUSIONS: Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions.

A Systematic Bibliometric Analysis of High-Impact Articles in Critical Care Nephrology.

INTRODUCTION: Critical care nephrology is a subspecialty that merges critical care and nephrology in response to shared pathobiology, clinical care, and technological innovations. To date, there has been no description of the highest impact articles. Accordingly, we systematically identified high impact articles in critical care nephrology. METHODS: This was a bibliometric analysis. The search was developed by a research librarian. Web of Science was searched for articles published between January 1, 2000 and December 31, 2020. Articles required a minimum of 30 citations, publication in English language, and reporting of primary (or secondary) original data. Articles were screened by two reviewers for eligibility and further adjudicated by three experts. The "Top 100" articles were hierarchically ranked by adjudication, citations in the 2 years following publication and journal impact factor (IF). For each article, we extracted detailed bibliometric data. Risk of bias was assessed for randomized trials by the Cochrane Risk of Bias tool. Analyses were descriptive. RESULTS: The search yielded 2,805 articles. Following initial screening, 307 articles were selected for full review and adjudication. The Top 100 articles were published across 20 journals (median [IQR] IF 10.6 [8.9-56.3]), 38% were published in the 5 years ending in 2020 and 62% were open access. The agreement between adjudicators was excellent (intraclass correlation, 0.96; 95% CI, 0.84-0.99). Of the Top 100, 44% were randomized trials, 35% were observational, 14% were systematic reviews, 6% were nonrandomized interventional studies and one article was a consensus document. The risk of bias among randomized trials was low. Common subgroup themes were RRT (42%), AKI (30%), fluids/resuscitation (14%), pediatrics (10%), interventions (8%), and perioperative care (6%). The citations for the Top 100 articles were 175 (95-393) and 9 were cited >1,000 times. CONCLUSION: Critical care nephrology has matured as an important subspecialty of critical care and nephrology. These high impact papers have focused largely on original studies, mostly clinical trials, within a few core themes. This list can be leveraged for curricula development, to stimulate research, and for quality assurance.

Initiation of continuous renal replacement therapy versus intermittent hemodialysis in critically ill patients with severe acute kidney injury: a secondary analysis of STARRT-AKI trial.

BACKGROUND: There is controversy regarding the optimal renal-replacement therapy (RRT) modality for critically ill patients with acute kidney injury (AKI). METHODS: We conducted a secondary analysis of the STandard versus Accelerated Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial to compare outcomes among patients who initiated RRT with either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD). We generated a propensity score for the likelihood of receiving CRRT and used inverse probability of treatment with overlap-weighting to address baseline inter-group differences. The primary outcome was a composite of death or RRT dependence at 90-days after randomization. RESULTS: We identified 1590 trial participants who initially received CRRT and 606 who initially received IHD. The composite outcome of death or RRT dependence at 90-days occurred in 823 (51.8%) patients who commenced CRRT and 329 (54.3%) patients who commenced IHD (unadjusted odds ratio (OR) 0.90; 95% confidence interval (CI) 0.75-1.09). After balancing baseline characteristics with overlap weighting, initial receipt of CRRT was associated with a lower risk of death or RRT dependence at 90-days compared with initial receipt of IHD (OR 0.81; 95% CI 0.66-0.99). This association was predominantly driven by a lower risk of RRT dependence at 90-days (OR 0.61; 95% CI 0.39-0.94). CONCLUSIONS: In critically ill patients with severe AKI, initiation of CRRT, as compared to IHD, was associated with a significant reduction in the composite outcome of death or RRT dependence at 90-days.

The Quality of Discharge Summaries After Acute Kidney Injury.

Background: Acute kidney injury (AKI) increases the risk of hospital readmission, chronic kidney disease, and death. Therefore, effective communication in discharge summaries is essential for safe transitions of care. Objective: The objectives of this study were to determine the quality of discharge summaries in AKI survivors and identify predictors of higher quality discharge summaries. Design: Retrospective chart review. Setting: Tertiary care academic center in Ontario, Canada. Patients: We examined the discharge summary quality of 300 randomly selected adult patients who survived a hospitalization with AKI at our tertiary care hospital, stratified by AKI severity. We included 150 patients each from 2015 to 2016 and 2018 to 2019, before and after introduction of a post-AKI clinic in 2017. Measurements: We reviewed charts for 9 elements of AKI care to create a composite score summarizing discharge summary quality. Methods: We used multivariable logistic regression to identify predictors of discharge summary quality. Results: The median discharge summary composite score was 4/9 (interquartile range, 2-6). The least frequently mentioned elements were baseline creatinine (n = 55, 18%), AKI-specific follow-up labs (n = 66, 22%), and medication recommendations (n = 80, 27%). The odds of having a higher quality discharge summary (composite score ≥4/9) was greater for every increase in baseline creatinine of 25 µmol/L (adjusted odds ratio [aOR]: 1.27; 95% confidence interval [CI]: 1.03, 1.56), intrarenal etiology (aOR: 2.32; 95% CI: 1.26, 4.27), and increased AKI severity (stage 2 aOR: 2.57; 95% CI: 1.35, 4.91 and stage 3 aOR: 3.36; 95% CI: 1.56, 7.22). There was no association between discharge summary quality and the years before and after introduction of a post-AKI clinic (aOR: 0.77; 95% CI: 0.46, 1.29). Limitations: The single-center study design limits generalizability. Conclusions: Most discharge summaries are missing key AKI elements, even in patients with severe AKI. These gaps suggest several opportunities exist to improve discharge summary communication following AKI.

Contexte: L'insuffisance rénale aiguë (IRA) augmente le risque de réadmission à l'hôpital, d'insuffisance rénale chronique et de décès. Une communication efficace est essentielle dans le résumé de départ pour assurer une transition sécuritaire des soins. Objectifs: Cette étude visait à évaluer la qualité des résumés de départ des survivants d'un épisode d'IRA et à identifier les facteurs prédictifs d'un résumé de départ de meilleure qualité. Conception: Examen rétrospectif des dossiers médicaux. Cadre: Un centre universitaire de soins tertiaires d'Ottawa (Ontario) au Canada. Sujets: Nous avons examiné la qualité du résumé de départ de 300 patients adultes ayant survécu à une hospitalisation pour IRA dans notre hôpital de soins tertiaires. Les patients ont été sélectionnés au hasard et stratifiés selon la gravité de l'IRA. Nous avons retenu 150 patients pour la période 2015-2016 et 150 patients pour la période 2018-2019; soit les périodes précédant et suivant l'introduction d'une clinique post-IRA en 2017. Mesures: Nous avons examiné les dossiers médicaux à la recherche de neuf éléments des soins d'IRA afin de créer un score composite évaluant la qualité du résumé de départ. Méthodologie: La régression logistique multivariée a été employée pour identifier les facteurs prédictifs de la qualité d'un résumé de départ. Résultats: Le score composite médian était de 4/9 (intervalle interquartile: 2-6). Les éléments les moins souvent mentionnés dans le résumé de départ étaient le taux de créatinine initial (n= 55; 18 %), les analyses de laboratoires liées spécifiquement au suivi de l'IRA (n= 66; 22 %) et les recommandations portant sur la médication (n= 80; 27 %). Les probabilités d'avoir un résumé de départ de qualité supérieure (score composite ≥4/9) étaient plus élevées pour chaque augmentation de 25 µmol/L de la créatinine initiale (RC corrigé [RCc] = 1,27; IC 95: 1,03-1,56), lorsque l'étiologie était intrarénale (RCc: 2,32; IC 95: 1,26-4,27) et la gravité de l'IRA accrue ([stade 2] RCc: 2,57; IC 95: 1,35-4,91; et [stade 3] RCc: 3,36; IC 95: 1,56-7,22). Aucune association n'a été observée entre la qualité du résumé de départ et la période étudiée, soit avant ou après l'introduction de la clinique post-IRA (RCc: 0,77; IC 95: 0,46-1,29). Limites: L'étude est monocentrique, ce qui limite la généralisabilité des résultats. Conclusion: Certains éléments clés des soins de l'IRA étaient absents de la plupart des résumés de départ, même chez les patients gravement atteints d'IRA. Ces lacunes indiquent qu'il est possible d'améliorer la communication du résumé de départ à la suite d'un épisode d'IRA.

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.

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.

Adverse events with quetiapine and clarithromycin coprescription: A population-based retrospective cohort study.

Background and Aims: Quetiapine is an atypical antipsychotic predominantly metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme. We studied the risk of adverse events following coprescription of clarithromycin (a strong CYP3A4 inhibitor) versus azithromycin (not a CYP3A4 inhibitor) in quetiapine users. Materials and Methods: This was a population-based retrospective cohort study from 2004 to 2020 in Ontario, Canada in adult quetiapine users newly co-prescribed clarithromycin (n = 16,909) or azithromycin (n = 25,267). The primary outcome was the composite of hospital encounters with encephalopathy (defined as a diagnosis of delirium, disorientation, transient alteration of awareness, transient ischemic attack, or unspecified dementia), a fall, or a fracture within 30 days of new coprescription. Secondary outcomes were individual components of the composite outcome, hospital encounter with computed tomography (CT) head scan, and all-cause mortality. Results: Coprescription of clarithromycin versus azithromycin with quetiapine was associated with a higher risk of the primary composite outcome (365 of 16,909 clarithromycin users [2.2%] vs. 309 of 16,929 azithromycin users [1.8%]; absolute risk increase, 0.34% [95% confidence interval, CI, 0.04-0.63]; relative risk [RR], 1.19 [95% CI, 1.02-1.38]). This was primarily driven by an increase in fragility fractures (78 of 16,909 clarithromycin users [0.5%] vs. 45 of 16,923 azithromycin users [0.3%]; absolute risk increase, 0.20% [95% CI, 0.07-0.32]; RR, 1.74 [95% CI, 1.21-2.52]). Hospital encounters with a CT head scan were higher in clarithromycin users (220 of 16,909 [1.3%] vs. 175 of 16,923 azithromycin users [1.0%]; absolute risk increase, 0.27% [95% CI, 0.04-0.50]; RR, 1.26 [95% CI, 1.04-1.54]), but there was no difference in hospital encounters with encephalopathy, falls, or all-cause mortality between macrolide groups. Conclusion: Among adults taking quetiapine, concurrent use of clarithromycin compared with azithromycin was associated with a small but statistically greater 30-day risk of a hospital encounter for encephalopathy, falls, or fracture, which was predominantly related to a higher rate of fragility fractures.

Predictive Models for Kidney Recovery and Death in Patients Continuing Dialysis as Outpatients after Starting in Hospital.

BACKGROUND: For patients who initiate dialysis during a hospital admission and continue to require dialysis after discharge, outpatient dialysis management could be improved by better understanding the future likelihood of recovery to dialysis independence and the competing risk of death. METHODS: We derived and validated linked models to predict the subsequent recovery to dialysis independence and death within 1 year of hospital discharge using a population-based cohort of 7657 patients in Ontario, Canada. Predictive variables included age, comorbidities, length of hospital admission, intensive care status, discharge disposition, and prehospital admission eGFR and random urine albumin-to-creatinine ratio. Models were externally validated in 1503 contemporaneous patients from Alberta, Canada. Both models were created using proportional hazards survival analysis, with the "Recovery Model" using Fine-Gray methods. Probabilities generated from both models were used to develop 16 distinct "Recovery and Death in Outpatients" (ReDO) risk groups. RESULTS: ReDO risk groups in the derivation group had significantly distinct 1-year probabilities for recovery to dialysis independence (first quartile: 10% [95% confidence interval (CI), 9% to 11%]; fourth quartile: 73% [70% to 77%]) and for death (first quartile: 12% [11% to 13%]; fourth quartile: 46% [43% to 50%]). In the validation group, model discrimination was modest (c-statistics [95% CI] for recovery and for death quartiles were 0.70 [0.67 to 0.73] and 0.66 [0.62 to 0.69], respectively), but calibration was excellent (integrated calibration index [95% CI] was 7% [5% to 9%] and 4% [2% to 6%] for recovery and death, respectively). CONCLUSIONS: The ReDO models generated accurate expected probabilities of recovery to dialysis independence and death in patients who continued outpatient dialysis after initiating dialysis in hospital. An online tool on the basis of the models is available at https://qxmd.com/calculate/calculator_874 .

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.

Fluid Management for Critically Ill Patients with Acute Kidney Injury Receiving Kidney Replacement Therapy: An International Survey.

BACKGROUND: In critically ill patients receiving KRT, high ultrafiltration rates and persistent fluid accumulation are associated with adverse outcomes. The purpose of this international survey was to evaluate current practices and evidence gaps related to fluid removal with KRT in critically ill patients. METHODS: This was a multinational, web-based survey distributed by seven networks comprising nephrologists and intensivists. Physicians involved in the care of critically ill patients were invited to complete a 39-question survey about fluid management practices on KRT. The survey was distributed from September 2021 to December 2021. RESULTS: There were 757 respondents from 96 countries (response rate of 65%). Most respondents practiced adult medicine (89%) and worked in an academic center (69%). The majority (91%) reported aiming for a 0.5- to 2-L negative fluid balance per day when fluid removal is indicated, although there was important variability in what respondents considered a safe maximal target. Intensivists were more likely than nephrologists to use adjunct volume status assessment methods ( i.e. , ultrasound, hemodynamic markers, and intra-abdominal pressure), while nephrologists were more likely to deploy cointerventions aimed at improving tolerance to fluid removal ( i.e. , osmotic agents and low-temperature dialysate). There was a broad consensus that rapid decongestion should be prioritized when fluid accumulation is present, but the prevention of hypotension was also reported as a competing priority. A majority (77%) agreed that performing trials that compare fluid management strategies would be ethical and clinically relevant. CONCLUSIONS: We have identified multiple areas of variability in current practice of fluid management for patients receiving KRT. Most nephrologists and intensivists agreed that several knowledge gaps related to fluid removal strategies should be investigated in future randomized controlled trials.

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.

Magnesium and Fracture Risk in the General Population and Patients Receiving Dialysis: A Narrative Review.

Purpose of Review: Magnesium is an essential mineral for bone metabolism, but little is known about how magnesium intake alters fracture risk. We conducted a narrative review to better understand how magnesium intake, through supplementation, diet, or altering the concentration of dialysate magnesium, affects mineral bone disease and the risk of fracture in individuals across the spectrum of kidney disease. Sources of Information: Peer-reviewed clinical trials and observational studies. Methods: We searched for relevant articles in MEDLINE and EMBASE databases. The methodologic quality of clinical trials was assessed using a modified version of the Downs and Black criteria checklist. Key Findings: The role of magnesium intake in fracture prevention is unclear in both the general population and in patients receiving maintenance dialysis. In those with normal kidney function, 2 meta-analyses showed higher bone mineral density in those with higher dietary magnesium, whereas 1 systematic review showed no effect on fracture risk. In patients receiving maintenance hemodialysis or peritoneal dialysis, a higher concentration of dialysate magnesium is associated with a lower concentration of parathyroid hormone, but little is known about other bone-related outcomes. In 2 observational studies of patients receiving hemodialysis, a higher concentration of serum magnesium was associated with a lower risk of hip fracture. Limitations: This narrative review included only articles written in English. Observed effects of magnesium intake in the general population may not be applicable to those with chronic kidney disease particularly in those receiving dialysis.

Justification: Le magnésium est un minéral essentiel pour le métabolisme osseux, mais on en sait peu sur la façon dont un apport en magnésium modifie le risque de fracture. Nous avons procédé à un examen narratif afin de mieux comprendre comment les maladies liées à la densité minérale osseuse et le risque de fracture sont affectés par un apport en magnésium (supplémentation, régime alimentaire ou modification de la concentration de dialysat de magnésium) chez les personnes atteintes d'insuffisance rénale. Sources: Essais cliniques et études observationnelles examinés par des pairs. Méthodologie: Nous avons répertorié les articles pertinents dans les bases de données MEDLINE et EMBASE. Une version modifiée des critères de contrôle de la qualité des études de Downs et Black a servi à évaluer la qualité méthodologique des essais cliniques retenus. Principaux résultats: Le rôle d'un apport en magnésium dans la prévention des fractures n'est pas clair, tant dans la population générale que chez les patients sous dialyse d'entretien. Chez les personnes ayant une fonction rénale normale, deux méta-analyses ont montré que les personnes dont le régime alimentaire est riche en magnésium présentent une densité minérale osseuse plus élevée; alors qu'une revue systématique n'a montré aucun effet sur le risque de fracture. Chez les patients sous hémodialyse d'entretien ou dialyse péritonéale, une concentration plus élevée de dialysat de magnésium est associée à une plus faible concentration d'hormone parathyroïdienne, mais on en sait peu sur les autres effets liés aux os. Dans deux études observationnelles portant sur des patients sous hémodialyse, une concentration plus élevée de magnésium sérique a été associée à un risque plus faible de fracture de la hanche. Limites: Cet examen narratif ne comprend que des articles rédigés en anglais. Il est possible que les effets d'un apport en magnésium observés dans la population générale ne puissent s'appliquer aux personnes atteintes d'une néphropathie chronique, en particulier aux personnes sous dialyse.

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.