Assessing Discharge Communication and Follow-up of Acute Kidney Injury in British Columbia: A Retrospective Chart Review.

Background and objective: Acute kidney injury (AKI) affects up to 20% of hospitalizations and is associated with chronic kidney disease, cardiovascular disease, increased mortality, and increased health care costs. Proper documentation of AKI in discharge summaries is critical for optimal monitoring and treatment of these patients once discharged. Currently, there is limited literature evaluating the quality of discharge communication after AKI. This study aimed to evaluate the accuracy and quality of documentation of episodes of AKI at a tertiary care center in British Columbia, Canada. Methods design setting patients and measurements: This was a retrospective chart review study of adult patients who experienced AKI during hospital admission between January 1, 2018, and December 31, 2018. Laboratory data were used to identify all admissions to the cardiac and general medicine ward complicated by AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. A random sample of 300 AKI admissions stratified by AKI severity (eg, stages 1, 2, and 3) were identified for chart review. Patients were excluded if they required ongoing renal replacement therapy after admission, had a history of kidney transplant, died during their admission, or did not have a discharge summary available. Discharge summaries were reviewed for documentation of the following: presence of AKI, severity of AKI, AKI status at discharge, practitioner and laboratory follow-up plans, and medication changes. Results: A total of 1076 patients with 1237 AKI admissions were identified. Of the 300 patients selected for discharge summary review, 38 met exclusion criteria. In addition, AKI was documented in 140 (53%) discharge summaries and was more likely to be documented in more severe AKI: stage 1, 38%; stage 2, 51%; and stage 3, 75%. Of those with their AKI documented, 94 (67%) documented AKI severity, and 116 (83%) mentioned the AKI status or trajectory at the time of discharge. A total of 239 (91%) of discharge summaries mentioned a follow-up plan with a practitioner, but only 23 (10%) had documented follow-up with nephrology. Patients with their AKI documented were more likely to have nephrology follow-up than those without AKI documented (17% vs 1%). Regarding laboratory investigations, 92 (35%) of the summaries had documented recommendations. In summaries that included medications typically held during AKI, only about half made specific reference to those medications being held, adjusted, or documented a post-discharge plan for that medication. For those with nonsteroidal anti-inflammatory drugs (NSAIDs) listing, 64% of discharge summaries mentioned holding, and 9% mentioned a discharge plan. For those with angiotensin converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) listing, 38% mentioned holding these medications, and 46% mentioned a discharge plan. In summaries with diuretics listed, 35% mentioned holding, and 51% included a discharge plan. Conclusions and limitations: We found suboptimal quality and completeness of discharge reporting in patients hospitalized with AKI. This may contribute to inadequate follow-up and post-hospitalization care for this patient population. Strategies are required for increasing the presence and quality of AKI reporting in discharge summaries. Limitations include our definition of AKI based on lab criteria, which may have missed some of the injuries that met the criteria based on urine output. Another limitation is that our definition of AKI based on the highest and lowest creatinine during admission may have led to some overclassification. In addition, without outpatient laboratories, it is possible that we have not captured the true baseline creatinine in some patients.

Contexte et objectif: L'insuffisance rénale aiguë (IRA) complique jusqu'à 20 % des hospitalisations; elle est associée à l'insuffisance rénale chronique, aux maladies cardiovasculaires, à une mortalité accrue et à une augmentation des coûts de santé. La documentation appropriée de l'IRA dans les résumés de départ est essentielle pour optimiser la surveillance et le traitement des patients après leur sortie de l'hôpital. Il existe peu de littérature évaluant la qualité de la documentation de l'IRA dans les résumés de départ. Cette étude visait à évaluer l'exactitude et la qualité de la documentation des épisodes d'IRA dans un center de soins tertiaires de la Colombie-Britannique (Canada). Méthodologie conception et cadre de l'étude sujets et mesures: Il s'agit d'une étude rétrospective des dossiers de patients adultes ayant présenté une IRA au cours de leur admission à l'hôpital entre le 1er janvier 2018 et le 31 décembre 2018. Les données de laboratoire ont été utilisées pour répertorier toutes les admissions compliquées par une IRA (définie par les critères KDIGO) dans les services de cardiologie et de médecine générale. Un échantillon aléatoire de 300 admissions avec IRA stratifiée selon sa gravité (p. ex., stade, 1, 2 et 3) a été constitué pour l'examen des dossiers. Ont été exclus les patients qui avaient eu besoin d'une thérapie de suppléance rénale continue après leur admission, ceux qui avaient des antécédents de transplantation rénale, ceux qui étaient décédés pendant leur admission et ceux pour qui aucun résumé de départ n'était disponible. Les résumés de départ ont été examinés à la recherche d'une mention des éléments suivants : présence d'une IRA, gravité de l'IRA, statut de l'IRA à la sortie, plans de suivi pour les tests de laboratoire et suivi avec un praticien, changements dans la médication. Résultats: En tout, 1 076 patients avec un total de 1 237 admissions avec IRA ont été identifiés. Parmi les 300 patients sélectionnés pour l'examen du résumé de départ, 38 répondaient aux critères d'exclusion. L'IRA avait été documentée dans 140 (53 %) des cas et plus elle était grave, plus elle était susceptible d'être documentée (stade 1 = 38 %; stade 2 = 51 %; stade 3 = 75 %). Parmi ceux où l'IRA était documentée, 94 (67 %) mentionnaient sa gravité et 116 (83 %) mentionnaient son statut ou sa trajectoire à la sortie du patient. Un plan de suivi avec le praticien était mentionné dans 239 (91 %) des résumés de départ, mais seuls 23 (10 %) mentionnaient un suivi en néphrologie. Les patients dont l'IRA était documentée étaient plus susceptibles de faire l'objet d'un suivi en néphrologie que ceux sans mention de l'IRA (17 % contre 1 %). En ce qui concerne les plans de suivi de laboratoire, 92 (35 %) des résumés contenaient des recommandations. Dans les résumés qui mentionnaient des médicaments normalement maintenus pendant un épisode d'IRA, seule la moitié environ faisait spécifiquement référence à ces médicaments comme ayant été cessés, ajustés ou documentés dans un plan post-sortie. Dans les résumés de départ qui listaient des AINS, 64 % mentionnaient qu'ils avaient été cessés temporairement et 9 % comprenaient un plan au congé de l'hôpital. Dans les résumés de départ qui listaient des IECA/ARA, 38 % mentionnaient que ces médicaments avaient été cessés temporairement et 46 % comprenaient un plan au congé de l'hôpital. Dans les résumés qui listaient des diurétiques, 35 % mentionnaient qu'ils avaient été cessés temporairement et 51 % comprenaient un plan au congé de l'hôpital. Limites et conclusion: Nous avons constaté que la qualité et l'exhaustivité des résumés de départ étaient sous-optimales chez les patients hospitalisés ayant vécu un épisode d'IRA. Cette situation peut contribuer à l'inadéquation du suivi et des soins post-hospitalization pour cette population de patients. Des stratégies sont nécessaires pour accroître la documentation d'un épisode d'IRA dans les résumés de départ et augmenter la qualité de sa communication. Les résultats de cette étude sont notamment limités par notre définition de l'IRA fondée sur des critères de laboratoire qui pourraient avoir manqué des patients répondant aux critères fondés sur la production d'urine. Notre définition de l'IRA fondée sur le taux de créatinine le plus élevée et le plus faible pendant l'admission pourrait également avoir conduit à un surdiagnostic. En outre, sans les résultats de laboratoires externes, il est possible que nous n'ayons pas saisi la mesure initiale réelle de la créatinine chez certains patients.

Cardiovascular Risk in Patients With Glomerular Disease: A Narrative Review of the Epidemiology, Mechanisms, Management, and Patient Priorities.

Purpose of review: Cardiovascular (CV) disease is a major cause of morbidity and mortality for patients with glomerular disease. Despite the fact that mechanisms underpinning CV disease risk in this population are likely distinct from other forms of kidney disease, treatment and preventive strategies tend to be extrapolated from studies of patients with undifferentiated chronic kidney disease (CKD). There is an unmet need to delineate the pathophysiology of CV disease in patients with glomerular disease, establish unique risk factors, and identify novel therapeutic targets for disease prevention. The aims of this narrative review are to summarize the existing knowledge regarding the epidemiology, molecular mechanisms, and management of CV disease in patients with common glomerular disease, highlight the patient perspective, and propose specific areas for future study. Sources of information: The literature for this narrative review was accessed using common research search engines, including PubMed, PubMed Central, Medline, and Google Scholar. Information for the patient perspective section was collected through iterative discussions with a patient partner. Methods: We reviewed the epidemiology, molecular mechanisms of disease, management approaches, and the patient perspective in relation to CV disease in patients with glomerulopathies. Throughout, we have highlighted the current knowledge and have discussed future research approaches, both clinical and translational, while integrating the patient perspective. Key findings: Patients with glomerular disease have significant CV disease risk driven by multifactorial, molecular mechanisms originating from their glomerular disease but complicated by existing comorbidities, kidney disease, and medication side effects. The current approach to risk stratification and treatment relies heavily on existing data from CKD patients, but this may not always be appropriate given the unique pathophysiology and mechanisms associated with CV disease risk in patients with glomerular disease. We highlight the need for ongoing glomerular disease-focused studies aimed to better delineate CV disease risk, while integrating the patient perspective. Limitations: This is a narrative review and does not represent a comprehensive and systematic review of the literature.

Motif de la revue: Les maladies cardiovasculaires sont une cause majeure de morbidité et de mortalité chez les patients atteints d'une maladie glomérulaire. Bien que les mécanismes qui sous-tendent le risque de maladie cardiovasculaire dans cette population sont probablement distincts des autres formes de néphropathies, le traitement et les stratégies préventives ont tendance à être extrapolés à partir d'études portant sur des patients atteints d'insuffisance rénale chronique indifférenciée. Il existe ainsi un besoin de délimiter la physiopathologie des maladies cardiovasculaires chez les patients atteints d'une maladie glomérulaire, d'établir les facteurs de risque propres à la maladie glomérulaire et d'identifier de nouvelles cibles thérapeutiques pour la prévenir. Les objectifs de cette revue narrative sont de résumer les connaissances existantes concernant l'épidémiologie, les mécanismes moléculaires et la prise en charge des maladies cardiovasculaires chez les patients atteints d'une maladie glomérulaire commune, de mettre en évidence le point de vue des patients et de proposer des domaines précis pour de futures études. Sources de l'information: La documentation a été consultée par le biais des moteurs de recherche courants, notamment PubMed, PubMed Central, Medline et Google Scholar. Les points de vue des patients ont été recueillis au moyen de discussions itératives avec un patient partenaire. Méthodologie: Nous avons examiné l'épidémiologie et les mécanismes moléculaires de la maladie, les approches de prise en charge et la perspective des patients en lien avec les maladies cardiovasculaires chez les patients atteints d'une maladie glomérulaire. Nous avons fait état des connaissances actuelles et discuté des approches à envisager pour les recherches futures, tant cliniques que translationnelles, tout en intégrant la perspective du patient. Principales observations: Les patients atteints d'une maladie glomérulaire présentent un risque significatif de maladie cardiovasculaire associé à des mécanismes moléculaires multifactoriels provenant de la maladie glomérulaire elle-même. Ce risque est compliqué par les comorbidités existantes, la néphropathie et les effets secondaires des médicaments. L'approche actuelle de stratification du risque et de traitement repose en grande partie sur les données existantes pour les patients atteints d'insuffisance rénale chronique; cette approche pourrait ne pas toujours convenir, compte tenu de la physiopathologie unique et des mécanismes associés au risque de maladie cardiovasculaire chez les patients atteints d'une maladie glomérulaire. Nos résultats mettent en lumière le besoin d'études continues, axées sur les maladies glomérulaires, qui visent à mieux cerner le risque de maladies cardiovasculaires chez ces patients, tout en intègrant leur point de vue. Limites: Il s'agit d'une revue narrative; cette étude ne constitue pas une revue exhaustive et systématique de la littérature.

Are patients with primary glomerular disease at increased risk of malignancy?

Over the past decade, several observational studies and case series have provided evidence suggesting a connection between glomerular diseases (GN) and the development of malignancies, with an estimated risk ranging from 5%-11%. These malignancies include solid organ tumors as well as hematologic malignancies such as lymphoma and leukemia. However, these risk estimates are subject to several sources of bias, including unmeasured confounding from inadequate exploration of risk factors, inclusion of GN cases that were potentially secondary to an underlying malignancy, misclassification of GN type, and ascertainment bias arising from an increased likelihood of physician encounters compared to the general population. Consequently, population-based studies that accurately evaluate the cancer risk in GN populations are lacking. While it is speculated that long-term use of immunosuppressive medications and GN disease activity measured by proteinuria and estimated glomerular filtration rate may be associated with cancer risk in patients with GN, the independent role of these risk factors remains largely unknown. The presence of these knowledge gaps could lead to (i) lack of awareness of cancer as a potential chronic complication of GN, (ii) under-utilization of routine screening practices in clinical care that allow early diagnosis and treatment of malignancies, and (iii) under-recognition of modifiable risk factors to decrease the risk of de novo malignancies over time. This review summarizes the current evidence on the risk of cancer in patients with GN, explores the limitations of prior studies, and discusses methodological challenges and potential solutions for obtaining accurate estimates of cancer risk and identifying modifiable risk factors unique to GN populations.

The Association Between Serum Vancomycin Level and Clinical Outcome in Patients With Peritoneal Dialysis Associated Peritonitis.

Introduction: Intraperitoneal (IP) vancomycin is often first-line empiric therapy and then maintenance therapy for peritoneal dialysis (PD) peritonitis. However, how vancomycin serum levels correlate with clinical outcomes remains unclear. Methods: We conducted a retrospective single-center adult cohort study of 98 patients with PD peritonitis treated with IP vancomycin between January 2016 and May 2022. The association between nadir vancomycin level and cure was evaluated in a logistic regression model, first unadjusted and then adjusted for age, sex, weight, glomerular filtration rate (GFR), and total number of days on PD. Vancomycin was assessed both as a continuous exposure (per 1 mg/l increase) and as a categorical exposure (<15 mg/l vs. ≥15 mg/l). A receiver operating characteristic curve (ROC) was created to explore nadir vancomycin level thresholds in an attempt to identify an optimal target level during treatment. Results: Of the patients, 81% achieved cure, and patients with nadir vancomycin level ≥15 mg/l were 7.5 times more likely to experience cure compared to those with a nadir level <15 mg/l (odds ratio [OR] 7.58, 95% confidence interval [CI] 1.71-33.57, P = 0.008). Weight, GFR, days on PD, sex, and age were not independently associated with outcome. The vancomycin level with the greatest discriminatory capacity for cure on the ROC analysis was 14.4 mg/l. Conclusion: Increasing IP vancomycin serum levels are associated with increased odds of cure; and maintaining vancomycin serum levels above 14-15 mg/l throughout the course of PD peritonitis treatment is likely to improve clinical outcomes.

Stroke Subtype Among Individuals With Chronic Kidney Disease.

Background: It is widely accepted that there is a stepwise increase in the risk of acute ischemic stroke with chronic kidney disease (CKD). However, whether the risk of specific ischemic stroke subtypes varies with CKD remains unclear. Objective: To assess the association between ischemic stroke subtypes (cardioembolic, arterial, lacunar, and other) classified using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) and CKD stage. Design: retrospective cohort study. Setting: Ontario, Canada. Patients: A total of 17 434 adults with an acute ischemic stroke in Ontario, Canada between April 1, 2002 and March 31, 2013, with an estimated glomerular filtration rate (eGFR) measurement or receipt of maintenance dialysis captured in a stroke registry were included. Measurements: Kidney function categorized as an eGFR of ≥60, 30-59, <30 mL/min/1.73 m2, or maintenance dialysis. Ischemic stroke classified by TOAST included arterial, cardioembolic, lacunar, and other (dissection, prothrombotic state, cortical vein/sinus thrombosis, and vasculitis) types of strokes. Methods: Adjusted regression models. Results: In our cohort, 58.9% had an eGFR of ≥60, 34.7% an eGFR of 30-59, 6.0% an eGFR of <30 and 0.5% were on maintenance dialysis (mean age of 73 years; 48% women). Cardioembolic stroke was more common in patients with non-dialysis-dependant CKD (eGFR 30-59: 50.4%, adjusted odds ratio [OR] 1.20, 95% confidence interval [CI]: 1.02, 1.44; eGFR<30: 50.6%, OR 1.21, 95% CI: 1.02, 1.44), whereas lacunar stroke was less common (eGFR 30-59: 22.7% OR 0.85, 95% CI: 0.77, 0.93; eGFR <30: 0.73, 95% CI: 0.61, 0.88) compared with those with an eGFR ≥60. In stratified analyses by age and CKD, lacunar strokes were more frequent in those aged less than 65 years, whereas cardioembolic was higher in those aged 65 years and above. Limitations: TOAST classification was not captured for all patients. Conclusion: Non-dialysis CKD was associated with a higher risk of cardioembolic stroke, whereas an eGFR ≥60 mL/min/1.73 m2 was associated with a higher risk of lacunar stroke. Detailed stroke subtyping in CKD may therefore provide mechanistic insights and refocus treatment strategies in this high-risk population.

Contexte: Il est largement admis qu'il y a une augmentation progressive du risque d'accident vasculaire cérébral ischémique aigu en contexte d'insuffisance rénale chronique (IRC). On ignore cependant si le risque de certains sous-types particuliers d'AVC ischémiques varie en présence d'IRC. Objectif: Évaluer le lien entre le stade d'IRC et certains sous-types d'AVC ischémiques (cardioembolique, artériel, lacunaire et autres) classés selon l'essai TOAST (Trial of ORG 10172 in Acute Stroke Treatment). Type d'étude: Étude de cohorte retrospective. Cadre: Ontario (Canada). Sujets: Ont été inclus 17 434 adultes ayant subi un AVC ischémique aigu en Ontario (Canada) entre le 1er avril 2002 et le 31 mars 2013, et pour lesquels le registre d'AVC comportait une mesure du débit de filtration glomérulaire estimé (DFGe) ou une dialyze chronique. Mesures: La fonction rénale a été classée selon le DFGe (≥ 60 ml/min/1,73 m2 ­entre 30 et 59 ml/min/1,73 m2 ­<30 ml/min/1.73 m2) ou une dialyze chronique. Les types d'AVC ischémiques classés par l'essai TOAST comprenaient les AVC artériels, cardioemboliques, lacunaires et autres (dissection, état prothrombotique, thrombose de la veine/sinus cortical, vascularite). Méthodologie: Modèles de régression ajustés. Résultats: Dans notre cohorte (âge moyen de 73 ans; 48% de femmes), 58,9 % des patients avaient un DFGe ≥ 60 ml/min/1,73 m2; 34,7% avaient un DFGe entre 30 et 59 ml/min/1,73 m2; 6,0 % avaient un DFGe < 30 ml/min/1,73 m2 et 0,5 % des patients étaient en dialyze chronique En comparaison des patients ayant un DFGe ≥ 60 ml/min/1,73 m2, les AVC cardioemboliques étaient plus fréquents chez les patients atteints d'IRC sans dialyze (DFGe entre 30 et 59 ml/min/1,73 m2: 50,4%; rapport de cote corrigé [RCc] = 1,20; IC 95 % = 1,02-1,44­DFGe < 30 ml/min/1,73 m2: 50,6 %; RCc = 1,21; IC95% = 1,02-1,44) alors que les AVC lacunaires étaient moins fréquents [DFGe entre 30 et 59 ml/min/1,73 m2: 22,7%; RCc = 0,85; IC 95% = 0,77-0,93­DFGe < 30 ml/min/1,73 m2: RCc = 0,73; IC 95% = 0,61-0,88]. Dans les analyses stratifiées en fonction de l'âge et de l'IRC, les AVC lacunaires étaient plus fréquents chez les moins de 65 ans tandis que les AVC cardioemboliques étaient plus fréquents chez les plus de 65 ans. Limites: La classification TOAST n'était pas enregistrée pour tous les patients. Conclusion: L'IRC sans dialyze a été associée à un risque plus élevé d'AVC cardioembolique alors qu'un DFGe ≥ 60 ml/min/1.73 m2 a été associé à un risque plus élevé d'AVC lacunaire. Le sous-typage détaillé des AVC en contexte d'IRC pourrait donc fournir des informations mécanistiques et recentrer les stratégies de traitement dans cette population à haut risque.

Regional Variation in Hemoglobin Distribution Among Individuals With CKD: the ISN International Network of CKD Cohorts.

Introduction: Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin. Methods: In this cross-sectional study, hemoglobin distribution was evaluated in each cohort overall and stratified by sex and estimated glomerular filtration rate (eGFR). Relationships between candidate predictors and hemoglobin were assessed from linear regression models in each cohort. Estimates were subsequently pooled in a random effects model. Results: A total of 58,613 participants from 21 adult cohorts (median eGFR range of 17-49 ml/min) and 3 pediatric cohorts (median eGFR range of 26-45 ml/min) were included with broad geographic representation. Hemoglobin values varied substantially among the cohorts, overall and within eGFR categories, with particularly low mean hemoglobin observed in women from Asian and African cohorts. Across the eGFR range, women had a lower hemoglobin compared to men, even at an eGFR of 15 ml/min (mean difference 5.3 g/l, 95% confidence interval [CI] 3.7-6.9). Lower eGFR, female sex, older age, lower body mass index, and diabetic kidney disease were all independent predictors of a lower hemoglobin value; however, this only explained a minority of variance (R2 7%-44% across cohorts). Conclusion: There are substantial regional differences in hemoglobin distribution among individuals with CKD, and the majority of variance is unexplained by demographics, eGFR, or comorbidities. These findings call for a renewed interest in improving our understanding of hemoglobin determinants in specific CKD populations.

Impaired Renal Function and Major Cardiovascular Events in Young Adults.

BACKGROUND: Cardiovascular (CV) disease in young adults (aged 18-39 years) is on the rise. Whether subclinical reductions in kidney function (ie, estimated glomerular filtration rate [eGFR] above the current threshold for chronic kidney disease but below age-expected values) are associated with elevated CV risk is unknown. OBJECTIVES: The goal of this study was to examine age-specific associations of subclinical eGFR reductions in young adults with major adverse cardiovascular events (MACEs) and MACE plus heart failure (MACE+). METHODS: A retrospective cohort study of 8.7 million individuals (3.6 million aged 18-39 years) was constructed using linked provincial health care data sets from Ontario, Canada (January 2008-March 2021). Cox models were used to examine the association of categorized eGFR (50-120 mL/min/1.73 m2) with MACE (first of CV mortality, acute coronary syndrome, and ischemic stroke) and MACE+, stratified according to age (18-39, 40-49, and 50-65 years). RESULTS: In the study cohort (mean age 41.3 years; mean eGFR 104.2 mL/min/1.73 m2; median follow-up 9.2 years), a stepwise increase in the relative risk of MACE and MACE+ was observed as early as eGFR <80 mL/min/1.73 m2 in young adults (eg, for MACE, at eGFR 70-79 mL/min/1.73 m2, ages 18-30 years: 2.37 events per 1,000 person years [HR: 1.31; 95% CI: 1.27-1.40]; ages 40-49 years: 6.26 events per 1,000 person years [HR: 1.09; 95% CI: 1.06-1.12]; ages 50-65 years: 14.9 events per 1,000 person years [HR: 1.07; 95% CI: 1.05-1.08]). Results persisted for each MACE component and in additional analyses (stratifying according to past CV disease, accounting for albuminuria at index, and using repeated eGFR measures). CONCLUSIONS: In young adults, eGFR below age-expected values were associated with an elevated risk for MACE and MACE+, warranting age-appropriate risk stratification, proactive monitoring, and timely intervention.

Biomarkers in acute kidney injury: On the cusp of a new era?

The field of nephrology has been slow in moving beyond the utilization of creatinine as an indicator for chronic kidney disease and acute kidney injury (AKI). Early diagnosis and establishment of etiology, in particular, are important for treatment of AKI. In the setting of hospital-acquired AKI, tubular injury is more common, but acute interstitial nephritis (AIN) has a more treatable etiology. However, it is likely that AIN is under- or misdiagnosed due to current strategies that largely rely on clinical gestalt. In this issue of the JCI, Moledina and colleagues made an elegant case for the chemokine called C-X-C motif ligand 9 (CXCL9) as a biomarker of AIN. The authors used urine proteomics and tissue transcriptomics in patients with and without AIN to identify CXCL9 as a promising, noninvasive, diagnostic biomarker of AIN. These results have clinical implications that should catalyze future research and clinical trials in this space.

Incidence of and Risk Factors for Active Tuberculosis Disease in Individuals With Glomerular Disease: A Canadian Cohort Study.

RATIONALE & OBJECTIVE: Kidney failure is an established risk factor for active tuberculosis (TB) but the risk of TB has not been reported in specific kidney diseases. We sought to determine the incidence of and risk factors for active TB in patients with glomerular disease. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: A provincial kidney pathology registry (2000-2012) was used to identify 3,079 adult patients with IgA nephropathy, focal segmental glomerulosclerosis (FSGS), antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis, lupus nephritis, membranous nephropathy, minimal change disease, or "other" glomerular diseases in British Columbia, Canada. EXPOSURE: Predictors included demographics, immigration status, comorbidities, immunosuppression use, estimated glomerular filtration rate (eGFR), and proteinuria. OUTCOME: A diagnosis of active TB was ascertained using administrative data linkages and defined based on (1) the dispensation of 1 or more unique combinations of medications used to treat active TB, or (2) physician or hospital visits for active TB. ANALYTICAL APPROACH: The definition of TB was validated in an external cohort linked to the Provincial TB registry at the BC Centre for Disease Control (BCCDC). Standardized incidence ratios were calculated using the age-matched general population. Risk factors for active TB were identified using Cox proportional hazards regression analysis. RESULTS: The sensitivity and specificity of the outcome definition of active TB were 87.6% and 99.5%, respectively. During a median follow-up of 6.2 years, 41 patients developed active TB with an incidence of 197 of 100,000 person-years, approximately 23 times as high as the general population and>6 times higher than the threshold of 30 per 100,000 used to define high TB incidence. A high incidence was observed in all glomerular diseases (range, 110-403 per 100,000), in both Canadian- and foreign-born patients (range, 124-424 per 100,000), and in patients exposed or not to immunosuppression (282 vs 147 per 100,000). Factors associated with higher TB risk included immigration from a high-incidence country (HR, 3.90 [95% CI, 1.75-8.68]), diminished eGFR (HR, 2.81 [95% CI, 1.18-6.69]), higher levels of proteinuria (HR, 1.15 [95% CI, 1.04-1.27]), lupus nephritis (HR, 2.79 [95% CI, 1.37-5.68]), and immunosuppression use (HR, 2.13 [95% CI, 1.13-4.03]). LIMITATIONS: A relatively low number of events contributed to uncertainty in risk estimates. CONCLUSIONS: Patients with glomerular disease have a high incidence of active TB irrespective of disease type, demographics, or use of immunosuppression. Prospective studies are needed to evaluate the utility of screening for latent TB infection in this population. PLAIN-LANGUAGE SUMMARY: Patients with kidney failure are at high risk of developing tuberculosis (TB), a major infection that can be prevented by identifying and treating patients who have had prior exposure to TB. The risk of TB in specific kidney diseases is unknown. In this Canadian study of 3,079 patients with glomerular disease, a group of autoimmune kidney conditions, the rate of TB was 23 times higher than in the general population. The rate was high irrespective of the use of immunosuppressive drugs or whether patients had immigrated to Canada from another country. These findings suggest that screening patients with glomerular disease for prior TB exposure may be beneficial; however, this needs to be evaluated in a prospective study.

Managing Hyperkalemia in the Modern Era: A Case-Based Approach.

The last decade has seen tremendous advances in the prevention and treatment of recurrent hyperkalemia. In this narrative review, we aim to highlight contemporary data on key areas in the epidemiology and management of hyperkalemia. Focusing on drug-induced hyperkalemia (the implications of renin-angiotensin-aldosterone system inhibitors [RAASi] discontinuation and the role of mineralocorticoid receptor antagonists), newer concurrent therapies that modify potassium handling (sodium-glucose transporter 2 inhibitors [SGLT2i]), the introduction of new treatment agents (oral potassium binding agents), and the controversial role of dietary potassium restriction, we apply recent research findings and review the evidence in a case-based format.

Associations between modest reductions in kidney function and adverse outcomes in young adults: retrospective, population based cohort study.

OBJECTIVE: To study age specific associations of modest reductions in estimated glomerular filtration rate (eGFR) with adverse outcomes. DESIGN: Retrospective, population based cohort study. SETTING: Linked healthcare administrative datasets in Ontario, Canada. PARTICIPANTS: Adult residents (18-65 years) with at least one outpatient eGFR value (categorized in 10 unit increments from 50 mL/min/1.73m2 to >120 mL/min/1.73m2), with no history of kidney disease. MAIN OUTCOME MEASURES: eGFRs and hazard ratios of composite adverse outcome (all cause mortality, any cardiovascular event, and kidney failure) stratified by age (18-39 years, 40-49 years, and 50-65 years), and relative to age specific eGFR referents (100-110 mL/min/1.73m2) for ages 18-39 years, 90-100 for 40-49 years, 80-90 for 50-65 years). RESULTS: From 1 January 2008 to 31 March 2021, among 8 703 871 adults (mean age 41.3 (standard deviation 13.6) years; mean index eGFR 104.2 mL/min/1.73m2 (standard deviation 16.1); median follow-up 9.2 years (interquartile range 5.7-11.4)), modestly reduced eGFR measurements specific to age were recorded in 18.0% of those aged 18-39, 18.8% in those aged 40-49, and 17.0% in those aged 50-65. In comparison with age specific referents, adverse outcomes were consistently higher by hazard ratio and incidence for ages 18-39 compared with older groups across all eGFR categories. For modest reductions (eGFR 70-80 mL/min/1.73m2), the hazard ratio for ages 18-39 years was 1.42 (95% confidence interval 1.35 to 1.49), 4.39 per 1000 person years; for ages 40-49 years was 1.13 (1.10 to 1.16), 9.61 per 1000 person years; and for ages 50-65 years was 1.08 (1.07 to 1.09), 23.4 per 1000 person years. Results persisted for each individual outcome and in many sensitivity analyses. CONCLUSIONS: Modest eGFR reductions were consistently associated with higher rates of adverse outcomes. Higher relative hazards were most prominent and occurred as early as eGFR <80 mL/min/1.73m2 in younger adults, compared with older groups. These findings suggest a role for more frequent monitoring of kidney function in younger adults to identify individuals at risk to prevent chronic kidney disease and its complications.

Risk of venous thromboembolism or hemorrhage among individuals with chronic kidney disease on prophylactic anticoagulant after hip or knee arthroplasty.

Chronic kidney disease (CKD) confers a high risk of thrombosis and bleeding. However, little evidence exists regarding the optimal choice of postoperative thromboprophylaxis in these patients. We conducted a population-based, retrospective cohort study among adults ≥66 years old with CKD undergoing hip or knee arthroplasty who had filled an outpatient prophylactic anticoagulant prescription between 2010 and 2020 in Ontario, Canada. The primary outcomes of venous thrombosis (VTE) and hemorrhage were identified by validated algorithms using relevant diagnoses and billing codes. Overlap-weighted cause-specific Cox proportional hazard models were used to examine the association of direct oral anticoagulants (DOAC) on the 90-day risk of VTE and hemorrhage compared with low-molecular-weight heparin (LMWH). A total of 27 645 patients were prescribed DOAC (N = 22 943) or LMWH (N = 4702) after arthroplasty. Rivaroxaban was the predominant DOAC (94.5%), while LMWH mainly included enoxaparin (67%) and dalteparin (31.5%). DOAC users had higher eGFRs, fewer co-morbidities, and surgery in more recent years compared to LMWH users. After weighing, DOAC (compared with LMWH) was associated with a lower risk of VTE (DOAC: 1.5% vs. LMWH: 2.1%, weighted hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.59-0.94) and a higher risk of hemorrhage (DOAC: 1.3% vs. LMWH: 1.0%, weighted HR 1.44, 95% CI 1.04-1.99). Additional analyses including a more stringent VTE defining algorithm, different eGFR cut-offs, and limiting to rivaroxaban and enoxaparin showed consistent findings. Among elderly adults with CKD, DOAC was associated with a lower VTE risk and a higher hemorrhage risk compared to LMWH following hip or knee arthroplasty.

Recent updates in kidney risk prediction modeling: novel approaches and earlier outcomes.

PURPOSE OF REVIEW: Recent years have witnessed the development of kidney risk prediction models which diverge from traditional model designs to incorporate novel approaches along with a focus on earlier outcomes. This review summarizes these recent advances, evaluates their pros and cons, and discusses their potential implications. RECENT FINDINGS: Several kidney risk prediction models have recently been developed utilizing machine learning rather than traditional Cox regression. These models have demonstrated accurate prediction of kidney disease progression, often beyond that of traditional models, in both internal and external validation. On the opposite end of the spectrum, a simplified kidney risk prediction model was recently developed which minimized the need for laboratory data and instead relies primarily on self-reported data. While internal testing showed good overall predictive performance, the generalizability of this model remains uncertain. Finally, there is a growing trend toward prediction of earlier kidney outcomes (e.g., incident chronic kidney disease [CKD]) and away from a sole focus on kidney failure. SUMMARY: Newer approaches and outcomes now being incorporated into kidney risk prediction modeling may enhance prediction and benefit a broader patient population. However, future work should address how best to implement these models into practice and assess their long-term clinical effectiveness.

Predictors of serum vancomycin levels in peritoneal dialysis-associated peritonitis.

BACKGROUND: Intraperitoneal (IP) vancomycin is often first-line empiric therapy for peritoneal dialysis (PD) peritonitis; however, whether dosing should be adjusted for patient-specific characteristics remains unclear. We sought to identify factors associated with the day 3 vancomycin serum level in patients receiving vancomycin for PD peritonitis. METHODS: Retrospective single-centre adult cohort of 58 patients with PD peritonitis treated with IP vancomycin between January 2016 and May 2022. Linear regression was used to examine the association between day 3 vancomycin level and candidate predictors including age, sex, weight, glomerular filtration rate (GFR), urea and creatinine clearance (total, residual, dialysate), PD modality, peritoneal solute transfer rate and initial vancomycin dose. Logistic regression was used to evaluate the likelihood of achieving a level (≥15 mg/L) associated with these predictor variables. RESULTS: A 2-g loading dose was given in 51 cases, and 38 patients (66%) had a therapeutic day 3 level. Each 5 mg/kg increase in initial vancomycin dose was associated with a 1.38 mg/L (95% confidence interval 0.52, 2.23) increase in day 3 level. Each 1 mL/min increase in GFR was associated with a 0.29 mg/L decrease (95% confidence interval 0.05, 0.52) in day 3 level. The likelihood of achieving a therapeutic level was approximately four times higher with an initial dose of ≥25 mg/kg compared to <25 mg/kg (odds ratio 3.75, 95% confidence interval 1.05, 13.46). CONCLUSIONS: Following an average 2-g vancomycin loading dose for suspected PD peritonitis, one-third of patients were subtherapeutic on day 3. GFR and weight-based dosing were independently associated with day 3 vancomycin level, and their consideration could improve the likelihood of achieving an early therapeutic level.

Management of Intermittent Hemodialysis in the Critically Ill Patient.

Intermittent hemodialysis remains a cornerstone of extracorporeal KRT in the intensive care unit, either as a first-line therapy for AKI or a second-line therapy when patients transition from a continuous or prolonged intermittent therapy. Intermittent hemodialysis is usually provided 3 days per week in this setting on the basis that no clinical benefits have been demonstrated with more frequent hemodialysis. This should not detract from the importance of continually assessing and refining the hemodialysis prescription (including the need for extra treatments) according to dynamic changes in extracellular volume and other parameters, and ensuring that an adequate dose of hemodialysis is being delivered to the patient. Compared with other KRT modalities, the cardinal challenge encountered during intermittent hemodialysis is hemodynamic instability. This phenomenon occurs when reductions in intravascular volume, as a consequence of ultrafiltration and/or osmotic shifts, outpace compensatory plasma refilling from the extravascular space. Myocardial stunning, triggered by intermittent hemodialysis, and independent of ultrafiltration, may also contribute. The hemodynamic effect of intermittent hemodialysis is likely magnified in patients who are critically ill due to an inability to mount sufficient compensatory physiologic responses in the context of multiorgan dysfunction. Of the many interventions that have undergone testing to mitigate hemodynamic instability related to KRT, the best evidence exists for cooling the dialysate and raising the dialysate sodium concentration. Unfortunately, the evidence supporting routine use of these and other interventions is weak owing to poor study quality and limited sample sizes. Intermittent hemodialysis will continue to be an important and commonly used KRT modality for AKI in patients with critical illness, especially in jurisdictions where resources are limited. There is an urgent need to harmonize the definition of hemodynamic instability related to KRT in clinical trials and robustly test strategies to combat it in this vulnerable patient population.

A Population-Based Analysis of the Risk of Glomerular Disease Relapse after COVID-19 Vaccination.

BACKGROUND: Although case reports have described relapses of glomerular disease after COVID-19 vaccination, evidence of a true association is lacking. In this population-level analysis, we sought to determine relative and absolute risks of glomerular disease relapse after COVID-19 vaccination. METHODS: In this retrospective population-level cohort study, we used a centralized clinical and pathology registry (2000-2020) to identify 1105 adult patients in British Columbia, Canada, with biopsy-proven glomerular disease that was stable on December 14, 2020 (when COVID-19 vaccines first became available). The primary outcome was disease relapse, on the basis of changes in kidney function, proteinuria, or both. Vaccination was modeled as a 30-day time-varying exposure in extended Cox regression models, stratified on disease type. RESULTS: During 281 days of follow-up, 134 (12.1%) patients experienced a relapse. Although a first vaccine dose was not associated with relapse risk (hazard ratio [HR]=0.67; 95% confidence interval [95% CI], 0.33 to 1.36), exposure to a second or third dose was associated with a two-fold risk of relapse (HR=2.23; 95% CI, 1.06 to 4.71). The pattern of relative risk was similar across glomerular diseases. The absolute increase in 30-day relapse risk associated with a second or third vaccine dose varied from 1%-2% in ANCA-related glomerulonephritis, minimal change disease, membranous nephropathy, or FSGS to 3%-5% in IgA nephropathy or lupus nephritis. Among 24 patients experiencing a vaccine-associated relapse, 4 (17%) had a change in immunosuppression, and none required a biopsy. CONCLUSIONS: In a population-level cohort of patients with glomerular disease, a second or third dose of COVID-19 vaccine was associated with higher relative risk but low absolute increased risk of relapse.

The value of repeat kidney biopsy during an atypical course of membranous nephropathy.

BACKGROUND: The clinical trajectory for patients with primary membranous nephropathy ranges widely from spontaneous remission to a rapid decline in kidney function. Etiologies for rapid progression with membranous nephropathy include concurrent bilateral renal vein thrombosis, malignant hypertension, and crescentic membranous nephropathy. Given the wide heterogeneity in prognosis, timing of immunosuppressive therapy is often challenging and centers around an individual patient's perceived risk for rapidly progressive disease. CASE PRESENTATION: Herein, we describe the clinical course of a young patient who initially developed a typical presentation of membranous nephropathy with consistent kidney biopsy findings. Given clinical stability, a six month observation period was undertaken prior to initiating immunosuppression. Within this observation window, the patient developed community acquired pneumonia followed several weeks later by a sudden, rapid decline in kidney function requiring dialysis. Repeat kidney biopsy revealed post-infectious glomerulonephritis superimposed upon a background of membranous nephropathy. Immunosuppressive therapy resulted in a favorable long-term outcome with normalization of kidney function and remission of nephrotic syndrome. To our knowledge, this is the first report of the simultaneous occurrence of these two glomerular disease processes. CONCLUSION: This case illustrates the value of repeat kidney biopsy during an atypical course of membranous nephropathy. Superimposed glomerular disease processes should be considered during a course of rapidly progressive membranous nephropathy.

The Risk of Cardiovascular Events in Individuals With Primary Glomerular Diseases.

RATIONALE & OBJECTIVE: Little is known about the risk of cardiovascular disease (CVD) in patients with various primary glomerular diseases. In a population-level cohort of adults with primary glomerular disease, we sought to describe the risk of CVD compared with the general population and the impact of traditional and kidney-related risk factors on CVD risk. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Adults with membranous nephropathy (n = 387), minimal change disease (n = 226), IgA nephropathy (n = 759), and focal segmental glomerulosclerosis (n = 540) from a centralized pathology registry in British Columbia, Canada (2000-2012). EXPOSURE: Traditional CVD risk factors (diabetes, age, sex, dyslipidemia, hypertension, smoking, prior CVD) and kidney-related risk factors (type of glomerular disease, estimated glomerular filtration rate [eGFR], proteinuria). OUTCOME: A composite CVD outcome of coronary artery, cerebrovascular, and peripheral vascular events, and death due to myocardial infarction or stroke. ANALYTICAL APPROACH: Subdistribution hazards models to evaluate the outcome risk with non-CVD death treated as a competing event. Standardized incidence rates (SIR) calculated based on the age- and sex-matched general population. RESULTS: During a median 6.8 years of follow-up, 212 patients (11.1%) experienced the CVD outcome (10-year risk, 14.7% [95% CI, 12.8%-16.8%]). The incidence rate was high for the overall cohort (24.7 per 1,000 person-years) and for each disease type (range, 12.2-46.1 per 1,000 person-years), and was higher than that observed in the general population both overall (SIR, 2.46 [95% CI, 2.12-2.82]) and for each disease type (SIR range, 1.38-3.98). Disease type, baseline eGFR, and proteinuria were associated with a higher risk of CVD and, when added to a model with traditional risk factors, led to improvements in model fit (R2 of 14.3% vs 12.7%), risk discrimination (C-statistic of 0.81 vs 0.78; difference, 0.02 [95% CI, 0.01-0.04]), and continuous net reclassification improvement (0.4 [95% CI, 0.2-0.6]). LIMITATIONS: Ascertainment of outcomes and comorbidities using administrative data. CONCLUSIONS: Patients with primary glomerular disease have a high absolute risk of CVD that is approximately 2.5 times that of the general population. Consideration of eGFR, proteinuria, and type of glomerular disease may improve risk stratification of CVD risk in these individuals. PLAIN-LANGUAGE SUMMARY: Patients with chronic kidney disease are known to be at high risk of cardiovascular disease. Cardiovascular risk in patients with primary glomerular diseases is poorly understood because these conditions are rare and require a kidney biopsy for diagnosis. In this study of 1,912 Canadian patients with biopsy-proven IgA nephropathy, minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy, the rate of cardiovascular events was 2.5 times higher than in the general population and was high for each disease type. Consideration of disease type, kidney function, and proteinuria improved the prediction of cardiovascular events. In summary, our population-level study showed that patients with primary glomerular diseases have a high cardiovascular risk, and that inclusion of kidney-specific risk factors may improve risk stratification.