Proximal versus distal diuretics in congestive heart failure.

Volume overload represents a hallmark clinical feature linked to the development and progression of heart failure (HF). Alleviating signs and symptoms of volume overload represents a foundational HF treatment target that is achieved using loop diuretics in the acute and chronic setting. Recent work has provided evidence to support guideline-directed medical therapies, such as sodium glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor (MR) antagonists, as important adjunct diuretics that may act synergistically when used with background loop diuretics in people with chronic HF. Furthermore, there is growing interest in understanding the role of SGLT2 inhibitors, carbonic anhydrase inhibitors, thiazide diuretics, and MR antagonists in treating volume overload in patients hospitalized for acute HF, particularly in the setting of loop diuretic resistance. Thus, the current review demonstrates that: 1) SGLT2 inhibitors and MR antagonists confer long-term cardioprotection in chronic HF patients but it is unclear if natriuresis or diuresis represents the primary mechanisms for this benefit, 2) SGLT2 inhibitors, carbonic anhydrase inhibitors, and thiazide diuretics increase natriuresis in the acute HF setting, but implications on long-term outcomes remain unclear and warrants further investigation, and 3) a multi-nephron segment approach, using agents that act on distinct segments of the nephron, potentiate diuresis to alleviate signs and symptoms of volume overload in acute HF.

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.

Vaccine Effectiveness Against SARS-CoV-2 Infection and Severe Outcomes in the Maintenance Dialysis Population in Ontario, Canada.

BACKGROUND: Vaccination studies in the hemodialysis population have demonstrated decreased antibody response compared with healthy controls, but vaccine effectiveness for preventing SARS-CoV-2 infection and severe disease is undetermined. METHODS: We conducted a retrospective cohort study in the province of Ontario, Canada, between December 21, 2020, and June 30, 2021. Receipt of vaccine, SARS-CoV-2 infection, and related severe outcomes (hospitalization or death) were determined from provincial health administrative data. Receipt of one and two doses of vaccine were modeled in a time-varying cause-specific Cox proportional hazards model, adjusting for baseline characteristics, background community infection rates, and censoring for non-COVID death, recovered kidney function, transfer out of province, solid organ transplant, and withdrawal from dialysis. RESULTS: Among 13,759 individuals receiving maintenance dialysis, 2403 (17%) were unvaccinated and 11,356 (83%) had received at least one dose by June 30, 2021. Vaccine types were BNT162b2 (n=8455, 74%) and mRNA-1273 (n=2901, 26%); median time between the first and second dose was 36 days (IQR 28-51). The adjusted hazard ratio (HR) for SARS-CoV-2 infection and severe outcomes for one dose compared with unvaccinated was 0.59 (95% CI, 0.46 to 0.76) and 0.54 (95% CI, 0.37 to 0.77), respectively, and for two doses compared with unvaccinated was 0.31 (95% CI, 0.22 to 0.42) and 0.17 (95% CI, 0.1 to 0.3), respectively. There were no significant differences in vaccine effectiveness among age groups, dialysis modality, or vaccine type. CONCLUSIONS: COVID-19 vaccination is effective in the dialysis population to prevent SARS-CoV-2 infection and severe outcomes, despite concerns about suboptimal antibody responses.

Differences in mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine immunogenicity among patients undergoing dialysis.

BACKGROUND: Differences in immunogenicity between mRNA SARS-CoV-2 vaccines have not been well characterized in patients undergoing dialysis. We compared the serologic response in patients undergoing maintenance hemodialysis after vaccination against SARS-CoV-2 with BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). METHODS: We conducted a prospective observational cohort study at 2 academic centres in Toronto, Canada, from Feb. 2, 2021, to July 20, 2021, which included 129 and 95 patients who received the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines, respectively. We measured SARS-CoV-2 immunoglobulin G antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD) and nucleocapsid protein (anti-NP) at 6-7 and 12 weeks after the second dose of vaccine and compared those levels with the median convalescent serum antibody levels from 211 controls who were previously infected with SARS-CoV-2. RESULTS: At 6-7 weeks after 2-dose vaccination, we found that 51 of 70 patients (73%) who received BNT162b2 and 83 of 87 (95%) who received mRNA-1273 attained convalescent levels of anti-spike antibody (p < 0.001). In those who received BNT162b2, 35 of 70 (50%) reached the convalescent level for anti-RBD compared with 69 of 87 (79%) who received mRNA-1273 (p < 0.001). At 12 weeks after the second dose, anti-spike and anti-RBD levels were significantly lower in patients who received BNT162b2 than in those who received mRNA-1273. For anti-spike, 70 of 122 patients (57.4%) who received BNT162b2 maintained the convalescent level versus 68 of 71 (96%) of those who received mRNA-1273 (p < 0.001). For anti-RBD, 47 of 122 patients (38.5%) who received BNT162b2 maintained the anti-RBD convalescent level versus 45 of 71 (63%) of those who received mRNA-1273 (p = 0.002). INTERPRETATION: In patients undergoing hemodialysis, mRNA-1273 elicited a stronger humoral response than BNT162b2. Given the rapid decline in immunogenicity at 12 weeks in patients who received BNT162b2, a third dose is recommended in patients undergoing dialysis as a primary series, similar to recommendations for other vulnerable populations.

COVID-19 Outbreak in an Urban Hemodialysis Unit.

RATIONALE & OBJECTIVE: Hemodialysis patients are at increased risk for coronavirus disease 2019 (COVID-19) transmission due in part to difficulty maintaining physical distancing. Our hemodialysis unit experienced a COVID-19 outbreak despite following symptom-based screening guidelines. We describe the course of the COVID-19 outbreak and the infection control measures taken for mitigation. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 237 maintenance hemodialysis patients and 93 hemodialysis staff at a single hemodialysis center in Toronto, Canada. EXPOSURE: Universal screening of patients and staff for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OUTCOMES: The primary outcome was detection of SARS-CoV-2 in nasopharyngeal samples from patients and staff using reverse transcriptase-polymerase chain reaction (RT-PCR). ANALYTICAL APPROACH: Descriptive statistics were used for clinical characteristics and the primary outcome. RESULTS: 11 of 237 (4.6%) hemodialysis patients and 11 of 93 (12%) staff members had a positive RT-PCR test result for SARS-CoV-2. Among individuals testing positive, 12 of 22 (55%) were asymptomatic at time of testing and 7 of 22 (32%) were asymptomatic for the duration of follow-up. One patient was hospitalized at the time of SARS-CoV-2 infection and 4 additional patients with positive test results were subsequently hospitalized. 2 (18%) patients required admission to the intensive care unit. After 30 days' follow-up, no patients had died or required mechanical ventilation. No hemodialysis staff required hospitalization. Universal droplet and contact precautions were implemented during the outbreak. Hemodialysis staff with SARS-CoV-2 infection were placed on home quarantine regardless of symptom status. Patients with SARS-CoV-2 infection, including asymptomatic individuals, were treated with droplet and contact precautions until confirmation of negative SARS-CoV-2 RT-PCR test results. Analysis of the outbreak identified 2 index cases with subsequent nosocomial transmission within the dialysis unit and in shared shuttle buses to the hemodialysis unit. LIMITATIONS: Single-center study. CONCLUSIONS: Universal SARS-CoV-2 testing and universal droplet and contact precautions in the setting of an outbreak appeared to be effective in preventing further transmission.

Obesity and the kidney: mechanistic links and therapeutic advances.

Obesity is strongly associated with the development of diabetes mellitus and chronic kidney disease (CKD), but there is evidence for a bidirectional relationship wherein the kidney also acts as a key regulator of body weight. In this Review, we highlight the mechanisms implicated in obesity-related CKD, and outline how the kidney might modulate feeding and body weight through a growth differentiation factor 15-dependent kidney-brain axis. The favourable effects of bariatric surgery on kidney function are discussed, and medical therapies designed for the treatment of diabetes mellitus that lower body weight and preserve kidney function independent of glycaemic lowering, including sodium-glucose cotransporter 2 inhibitors, incretin-based therapies and metformin, are also reviewed. In summary, we propose that kidney function and body weight are related in a bidirectional fashion, and that this interrelationship affects human health and disease.

Perceptions and Information-Seeking Behavior Regarding COVID-19 Vaccination Among Patients With Chronic Kidney Disease in 2023: A Cross-Sectional Survey.

Background: People living with chronic kidney disease (CKD) face an increased risk of severe outcomes such as hospitalization or death from COVID-19. COVID-19 vaccination is a vital approach to mitigate the risk and severity of infection in patients with CKD. Limited information exists regarding the factors that shape COVID-19 vaccine uptake, including health information-seeking behavior and perceptions, within the CKD population. Objective: The objectives were to describe among CKD patients, (1) health information-seeking behavior on COVID-19, (2) their capacity to comprehend and trust COVID-19 information from different sources, and (3) their perceptions concerning COVID-19 infection and vaccination. Design/Setting: Cross-sectional web-based survey administered in British Columbia and Ontario from February 17, 2023, to April 17, 2023. Participants: Chronic kidney disease G3b-5D patients and kidney transplant recipients (CKD G1T-5T) enrolled in a longitudinal COVID-19 vaccine serology study. Methods and Measurements: The survey consisted of a questionnaire that included demographic and clinical data, perceived susceptibility of contracting COVID-19, the ability to collect, understand, and trust information on COVID-19, as well as perceptions regarding COVID-19 vaccination. Descriptive statistics were used to present the data with values expressed as count (%) and chi square tests were performed with a significance level set at P ≤ .05. A content analysis was performed on one open-ended response regarding respondents' questions surrounding COVID-19 infection and vaccination. Results: Among the 902 patients who received the survey via email, 201 completed the survey, resulting in a response rate of 22%. The median age was 64 years old (IQR 53-74), 48% were male, 51% were university educated, 32% were on kidney replacement therapies, and 57% had received ≥5 COVID-19 vaccine doses. 65% of respondents reported that they had sought out COVID-19-related information in the last 12 months, with 91% and 84% expressing having understood and trusted the information they received, respectively. Those with a higher number of COVID-19 vaccine doses were associated with having sought out (P =.017), comprehended (P < .001), and trusted (P =. 005) COVID-19-related information. Female sex was associated with expressing more concern about contracting COVID-19 (P = .011). Most respondents strongly agreed to statements regarding the benefits of COVID-19 vaccination. Respondents' questions about COVID-19 infection and vaccination centered on 4 major themes: COVID-19 vaccination strategy, vaccine effectiveness, vaccine safety, and the impact of COVID-19 infection and vaccination on kidney health. Limitations: This survey was administered within the Canadian health care context to patients with CKD who had at least 1 COVID-19 vaccine dose. Race/ethnicity of participants was not captured. Conclusions: In this survey of individuals with CKD, COVID-19 information-seeking behavior was high and almost all respondents understood and trusted the information they received. Perceptions toward the COVID-19 vaccine and booster were mostly favorable.

Humoral Response Following 3 Doses of mRNA COVID-19 Vaccines in Patients With Non-Dialysis-Dependent CKD: An Observational Study.

Background: Chronic kidney disease (CKD) is associated with a lower serologic response to vaccination compared to the general population. There is limited information regarding the serologic response to coronavirus disease 2019 (COVID-19) vaccination in the non-dialysis-dependent CKD (NDD-CKD) population, particularly after the third dose and whether this response varies by estimated glomerular filtration rate (eGFR). Methods: The NDD-CKD (G1-G5) patients who received 3 doses of mRNA COVID-19 vaccines were recruited from renal clinics within British Columbia and Ontario, Canada. Between August 27, 2021, and November 30, 2022, blood samples were collected serially for serological testing every 3 months within a 9-month follow-up period. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike, anti-receptor binding domain (RBD), and anti-nucleocapsid protein (NP) levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: Among 285 NDD-CKD patients, the median age was 67 (interquartile range [IQR], 52-77) years, 58% were men, 48% received BNT162b2 as their third dose, 22% were on immunosuppressive treatment, and COVID-19 infection by anti-NP seropositivity was observed in 37 of 285 (13%) patients. Following the third dose, anti-spike and anti-RBD levels peaked at 2 months, with geometric mean levels at 1131 and 1672 binding antibody units per milliliter (BAU/mL), respectively, and seropositivity rates above 93% and 85%, respectively, over the 9-month follow-up period. There was no association between eGFR or urine albumin-creatinine ratio (ACR) with mounting a robust antibody response or in antibody levels over time. The NDD-CKD patients on immunosuppressive treatment were less likely to mount a robust anti-spike response in univariable (odds ratio [OR] 0.43, 95% confidence interval [CI]: 0.20, 0.93) and multivariable (OR 0.52, 95% CI: 0.25, 1.10) analyses. An interaction between age, immunoglobulin G (IgG) antibody levels, and time was observed in both unadjusted (anti-spike: P = .005; anti-RBD: P = .03) and adjusted (anti-spike: P = .004; anti-RBD: P = .03) models, with older individuals having a more pronounced decline in antibody levels over time. Conclusion: Most NDD-CKD patients were seropositive for anti-spike and anti-RBD after 3 doses of mRNA COVID-19 vaccines and we did not observe any differences in the antibody response by eGFR.

Biology and Clinical Use of Glucagon-Like Peptide-1 Receptor Agonists in Vascular Protection.

Glucagon-like peptide-1 receptor agonists (GLP1RA) are incretin agents initially designed for the treatment of type 2 diabetes mellitus but because of pleiotropic actions are now used to reduce cardiovascular disease in people with type 2 diabetes mellitus and in some instances as approved treatments for obesity. In this review we highlight the biology and pharmacology of GLP1RA. We review the evidence for clinical benefit on major adverse cardiovascular outcomes in addition to modulation of cardiometabolic risk factors including reductions in weight, blood pressure, improvement in lipid profiles, and effects on kidney function. Guidance is provided on indications and potential adverse effects to consider. Finally, we describe the evolving landscape of GLP1RA and including novel glucagon-like peptide-1-based dual/polyagonist therapies that are being evaluated for weight loss, type 2 diabetes mellitus, and cardiorenal benefit.

Knowledge Translation in Glomerulonephritis: Successes in Translational Research From the Bench to Bedside.

Purpose of review: Glomerulonephritis refers to a rare group of diseases characterized by glomerular inflammation, which collectively are a common cause of kidney failure. Until recently, there was a lack of high-quality clinical trials to inform the care of patients with glomerulonephritides. We identified examples of successful translational research spanning from basic science to clinical applications, and highlight gaps in implementation science. Sources of information: The focus of our review was derived from discussions between health care professionals, researchers, and patient partners. We also performed literature searches pertaining to the treatment of glomerulonephritis in PubMed and Google Scholar. Methods: Examples of successful knowledge translation were generated through review of new evidence in the past 5 years and by iterative discussions by the authors. We then conducted a narrative review of several themes related to knowledge translation in glomerulonephritis. This was complemented by an interview with a patient partner to provide an example of a patient's perspective living with glomerulonephritis. Key findings: We summarized selected recent advances in glomerulonephritis and its knowledge translation in the following domains: (1) identification of auto-antibodies in membranous nephropathy and minimal change disease; (2) clinical trials of novel targeted therapies for IgA nephropathy and lupus nephritis, which have led to approval of new treatments; (3) developments in research networks and clinical trials in glomerulonephritis; (4) recognition of the importance in developing standardized patient reported outcome measures in clinical trials; and (5) barriers in knowledge translation including access to medication. Limitations: A systematic search of the literature and formal assessment of quality of evidence were beyond the scope of this review.

Motif de la revue: La glomérulonéphrite désigne un groupe rare de maladies qui se caractérisent par une inflammation des glomérules. Collectivement, ces maladies sont une cause fréquente d'insuffisance rénale. Jusqu'à récemment, il n'y avait pas d'essais cliniques de grande qualité pour guider les soins des patients atteints de glomérulonéphrites. Nous avons répertorié des exemples de recherches translationnelles réussies, allant de la recherche fondamentale aux applications cliniques, et nous avons mis en évidence les lacunes dans l'application de la science. Sources: L'essentiel de notre examen est dérivé de discussions entre les professionnels de la santé, les chercheurs et les patients partenaires. Nous avons également procédé à une revue de la littérature sur PubMed et Google Scholar portant sur le traitement de la glomérulonéphrite. Méthodologie: Des exemples d'application réussie des connaissances ont été générés par un examen des récentes données probantes (cinq dernières années) et par des discussions itératives entre les auteurs. Nous avons ensuite procédé à une revue narrative de plusieurs thèmes liés à l'application des connaissances en contexte de glomérulonéphrite. Cette démarche a été complétée par une entrevue avec une patiente partenaire, afin de fournir le point de vue d'une personne vivant avec une glomérulonéphrite. Principaux résultats: Nous avons résumé certaines des avancées récentes de la recherche sur la glomérulonéphrite et l'application des connaissances dans les domaines suivants: 1) l'identification d'auto-anticorps dans la glomérulonéphrite membraneuse et la néphropathie à lésion glomérulaire minime; 2) les essais cliniques portant sur de nouvelles thérapies ciblées pour la néphropathie à IgA et la néphrite lupique qui ont conduit à l'approbation de nouveaux traitements; 3) les développements dans les réseaux de recherche et les essais cliniques sur la glomérulonéphrite; 4) la reconnaissance de l'importance d'élaborer des mesures normalisées pour les résultats rapportés par les patients dans les essais cliniques; 5) les obstacles à l'application des connaissances, y compris l'accès aux médicaments. Limites: Une recherche systématique de la documentation et l'évaluation officielle de la qualité des preuves dépassaient la portée de cet examen.

SGLT-2 inhibitors in nephrotic-range proteinuria: emerging clinical evidence.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a class of novel oral anti-hyperglycemic agents which are increasingly used in clinical practice. SGLT-2 inhibitors improve glycemic control and cardiorenal outcomes, promote weight loss, and reduce blood pressure. Randomized controlled trials have demonstrated that SGLT-2 inhibitors reduce proteinuria and delay progression of kidney disease in patients with albuminuria. However, whether SGLT-2 inhibitors have similar benefits in patients with nephrotic-range proteinuria has not been well established. Evidence to date has been limited to case reports, case series and secondary analyses of randomized controlled trials. This is the first comprehensive review on the effectiveness of SGLT-2 inhibitors for the treatment of patients with nephrotic-range albuminuria or proteinuria. Overall findings support a likely beneficial role of SGLT-2 inhibitors in reducing proteinuria and delaying chronic kidney disease progression in patients with nephrotic-range proteinuria.

Humoral Responses in the Omicron Era Following 3-Dose SARS-CoV-2 Vaccine Series in Kidney Transplant Recipients.

Kidney transplant recipients (KTRs) have a diminished response to SARS-CoV-2 vaccination compared with immunocompetent individuals. Deeper understanding of antibody responses in KTRs following third-dose vaccination would enable identification of those who remain unprotected against Omicron. Methods: We profiled antibody responses in KTRs pre- and at 1 and 3 mo post-third-dose SARS-CoV-2 mRNA-based vaccine. Binding antibody levels were determined by ELISA. Neutralization against wild type, Beta, Delta, and Omicron (BA.1) variants was determined using a SARS-CoV-2 spike-pseudotyped lentivirus assay. Results: Forty-four KTRs were analyzed at 1 and 3 mo (n = 26) post-third dose. At 1 mo, the proportion of participants with a robust antibody response had increased significantly from baseline, but Omicron-specific neutralizing antibodies were detected in just 45% of KTRs. Median binding antibody levels declined at 3 mo, but the proportion of KTRs with a robust antibody response was unchanged; 38.5% KTRs maintained Omicron-specific neutralization at 3 mo. No clinical variables were significantly associated with Omicron-neutralizing antibodies, but antireceptor binding domain titers appeared to identify those with Omicron-specific neutralizing capacity. Conclusions: Over 50% of KTRs lack Omicron-specific neutralization capacity 1 mo post-third mRNA-vaccine dose. Antibody levels of responders were well preserved at 3 mo. Anti receptor binding domain antibody titers may identify patients with a detectable Omicron-neutralizing antibody response.

Evaluation of commercial assays for the assessment of SARS-CoV-2 antibody response in hemodialysis patients.

BACKGROUND: Hemodialysis patients exhibit variable immunogenicity following administration of the SARS-CoV-2 mRNA vaccine. The aim of the current study was to evaluate the use of two commercial assays in the assessment of SARS-CoV-2 antibody response in hemodialysis patients and to compare their utility to commonly used SARS-CoV-2 serological assays developed in Canada. METHODS: We evaluated serologic antibody response in 85 hemodialysis patients up to 6 months after receiving both doses of the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine. In addition, antibody response was assessed in 46 chronic kidney disease patients and 40 COVID-19 naïve health care workers (HCW) up to 3 months and 9 months, respectively. Anti-spike (S) and anti-nucleocapsid (N) levels were measured using Elecsys anti-SARS-CoV-2 immunoassays on the Roche analyzer and compared to ELISA-based detection of anti-S, anti-receptor binding domain (RBD), and anti-N. RESULTS: The Elecsys anti-N immunoassay showed 93 % concordance with the anti-N ELISA. The Elecsys anti-S immunoassay showed 97 % concordance with the anti-S ELISA and 89 % concordance with the anti-RBD ELISA. HCWs exhibited significantly higher anti-S levels relative to hemodialysis patients. Anti-S levels decreased significantly over a 6-month period (p < 0.001) in patients receiving maintenance hemodialysis. In addition, anti-S levels decreased significantly over a 9-month (p < 0.001) and 3-month period (p < 0.001) in HCWs and CKD patients, respectively. CONCLUSIONS: There is high concordance between commercial SARS-CoV-2 serological assays and SARS-CoV-2 serological assays developed in Canada. Hemodialysis patients exhibited varying immunogenicity following two doses of the COVID-19 mRNA vaccine with anti-S levels decreasing over time.

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.

Real-life use of tolvaptan in ADPKD: a retrospective analysis of a large Canadian cohort.

Tolvaptan is the first disease-modifying drug proven to slow eGFR decline in high-risk patients with ADPKD. However, barriers from the patient perspective to its use in real-life settings have not been systemically examined in a large cohort. This was a single-center, retrospective study of 523 existing or new patients with ADPKD followed at the Center for Innovative Management of PKD in Toronto, Ontario, between January 1, 2016 to December 31, 2018. All patients underwent clinical assessment including total kidney volume measurements and Mayo Clinic Imaging Class (MCIC). Those who were deemed to be at high risk were offered tolvaptan with their preference (yes or no) and reasons for their choices recorded. Overall, 315/523 (60%) patients had MCIC 1C-1E; however, only 96 (30%) of them were treated with tolvaptan at their last follow-up. Among these high-risk patients, those not treated versus treated with tolvaptan were more likely to have a higher eGFR (82 ± 26 vs. 61 ± 27 ml/min/1.73 m2), CKD stages 1-2 (79% vs. 41%), and MCIC 1C (63% vs. 31%). The most common reasons provided for not taking tolvaptan were lifestyle preference related to the aquaretic effect (51%), older age ≥ 60 (12%), and pregnancy/family planning (6%). In this real-world experience, at least 60% of patients with ADPKD considered to be at high risk for progression to ESKD by imaging were not treated with tolvaptan; most of them had early stages of CKD with well-preserved eGFR and as such, were prime targets for tolvaptan therapy to slow disease progression. Given that the most common reason for tolvaptan refusal was the concern for intolerability of the aquaretic side-effect, strategies to mitigate this may help to reduce this barrier to tolvaptan therapy.

Effectiveness of Three Doses of mRNA COVID-19 Vaccines in the Hemodialysis Population during the Omicron Period.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccine effectiveness studies in the hemodialysis population have demonstrated that two doses of mRNA COVID-19 vaccines are effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe complications when Alpha and Delta were predominant variants of concern. Vaccine effectiveness after a third dose versus two doses for preventing SARS-CoV-2 infection and severe COVID-19 in the hemodialysis population against Omicron is not known. METHODS: We conducted a retrospective cohort study in Ontario, Canada, between December 1, 2021, and February 28, 2022, in the maintenance hemodialysis population who had received two versus three doses of mRNA COVID-19 vaccines. COVID-19 vaccination, SARS-CoV-2 infection, and related hospitalization and death were determined from provincial databases. The primary outcome was the first RT-PCR confirmed SARS-CoV-2 infection, and the secondary outcome was a SARS-CoV-2-related severe outcome, defined as either hospitalization or death. RESULTS: A total of 8457 individuals receiving in-center hemodialysis were included. At study initiation, 2334 (28%) individuals received three doses, which increased to 7468 (88%) individuals by the end of the study period. The adjusted hazard ratios (aHR) for SARS-CoV-2 infection (aHR, 0.58; 95% confidence interval [CI], 0.50 to 0.67) and severe outcomes (hospitalization or death) (aHR, 0.40; 95% CI, 0.28 to 0.56) were lower after three versus two doses of mRNA vaccine. Prior infection, independent of vaccine status, was associated with a lower risk of reinfection, with an aHR of 0.44 (95% CI, 0.27 to 0.73). CONCLUSIONS: Three-dose mRNA COVID-19 vaccination was associated with lower incidence of SARS-CoV-2 infection and severe SARS-CoV-2-related outcomes during the Omicron period compared with two doses.

Omicron variant neutralizing antibodies following BNT162b2 BA.4/5 versus mRNA-1273 BA.1 bivalent vaccination in patients with end-stage kidney disease.

Neutralization of Omicron subvariants by different bivalent vaccines has not been well evaluated. This study characterizes neutralization against Omicron subvariants in 98 individuals on dialysis or with a kidney transplant receiving the BNT162b2 (BA.4/BA.5) or mRNA-1273 (BA.1) bivalent COVID-19 vaccine. Neutralization against Omicron BA.1, BA.5, BQ.1.1, and XBB.1.5 increased by 8-fold one month following bivalent vaccination. In comparison to wild-type (D614G), neutralizing antibodies against Omicron-specific variants were 7.3-fold lower against BA.1, 8.3-fold lower against BA.5, 45.8-fold lower against BQ.1.1, and 48.2-fold lower against XBB.1.5. Viral neutralization was not significantly different by bivalent vaccine type for wild-type (D614G) (P = 0.48), BA.1 (P = 0.21), BA.5 (P = 0.07), BQ.1.1 (P = 0.10), nor XBB.1.5 (P = 0.10). Hybrid immunity conferred higher neutralizing antibodies against all Omicron subvariants. This study provides evidence that BNT162b2 (BA.4/BA.5) and mRNA-1273 (BA.1) induce similar neutralization against Omicron subvariants, even when antigenically divergent from the circulating variant.