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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.
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Individualized pre-pregnancy counseling and antenatal care for women with chronic kidney disease (CKD) require disease-specific data. Here, we investigated pregnancy outcomes and long-term kidney function in women with COL4A3-5 related disease (Alport Syndrome, (AS)) in a large multicenter cohort. The ALPART-network (mAternaL and fetal PregnAncy outcomes of women with AlpoRT syndrome), an international collaboration of 17 centers, retrospectively investigated COL4A3-5 related disease pregnancies after the 20th week. Outcomes were stratified per inheritance pattern (X-Linked AS (XLAS)), Autosomal Dominant AS (ADAS), or Autosomal Recessive AS (ARAS)). The influence of pregnancy on estimated glomerular filtration rate (eGFR)-slope was assessed in 192 pregnancies encompassing 116 women (121 with XLAS, 47 with ADAS, and 12 with ARAS). Median eGFR pre-pregnancy was over 90ml/min/1.73m2. Neonatal outcomes were favorable: 100% live births, median gestational age 39.0 weeks and mean birth weight 3135 grams. Gestational hypertension occurred during 23% of pregnancies (reference: 'general' CKD G1-G2 pregnancies incidence is 4-20%) and preeclampsia in 20%. The mean eGFR declined after pregnancy but remained within normal range (over 90ml/min/1.73m2). Pregnancy did not significantly affect eGFR-slope (pre-pregnancy ß=-1.030, post-pregnancy ß=-1.349). ARAS-pregnancies demonstrated less favorable outcomes (early preterm birth incidence 3/11 (27%)). ARAS was a significant independent predictor for lower birth weight and shorter duration of pregnancy, next to the classic predictors (pre-pregnancy kidney function, proteinuria, and chronic hypertension) though missing proteinuria values and the small ARAS-sample hindered analysis. This is the largest study to date on AS and pregnancy with reassuring results for mild AS, though inheritance patterns could be considered in counseling next to classic risk factors. Thus, our findings support personalized reproductive care and highlight the importance of investigating kidney disease-specific pregnancy outcomes.
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Nefritis Hereditaria , Complicaciones del Embarazo , Nacimiento Prematuro , Insuficiencia Renal Crónica , Femenino , Humanos , Embarazo , Recién Nacido , Lactante , Resultado del Embarazo/epidemiología , Nefritis Hereditaria/genética , Peso al Nacer , Estudios Retrospectivos , Nacimiento Prematuro/etiología , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/genética , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/genética , Proteinuria , ConsejoRESUMEN
Pregnancy is an important goal for many women with CKD or kidney failure, but important barriers exist, particularly as CKD stage progresses. Women with advanced CKD often have a limited fertility window and may miss their opportunity for a pregnancy if advised to defer until after kidney transplantation. Pregnancy rates in women with advanced kidney failure or receiving dialysis remain low, and despite the improved outcomes in recent years, these pregnancies remain high risk for both mother and baby with high rates of preterm birth due to both maternal and fetal complications. However, with increased experience and advances in models of care, this paradigm may be changing. Intensive hemodialysis regimens have been shown to improve both fertility and live birth rates. Increasing dialysis intensity and individualizing dialysis prescription to residual renal function, to achieve highly efficient clearances, has resulted in improved live birth rates, longer gestations, and higher birth weights. Intensive hemodialysis regimens, particularly nocturnal and home-based dialysis, are therefore a potential option for women with kidney failure desiring pregnancy. Global initiatives for the promotion and uptake of home-based dialysis are gaining momentum and may have advantages in this unique patient population. In this article, we review the epidemiology and outcomes of pregnancy in hemodialysis and peritoneal dialysis recipients. We discuss the role home-based therapies may play in helping women achieve more successful pregnancies and outline the principles and practicalities of management of dialysis in pregnancy with a focus on delivery of home modalities. The experience and perspectives of a patient are also shared.
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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.
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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.
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COVID-19 , Insuficiencia Renal Crónica , Humanos , Vacunas contra la COVID-19 , SARS-CoV-2 , Formación de Anticuerpos , Vacuna BNT162 , COVID-19/diagnóstico , Anticuerpos Antivirales , Diálisis Renal , Insuficiencia Renal Crónica/terapiaRESUMEN
Introduction: Individuals with chronic kidney disease (CKD) are at increased risk of adverse pregnancy outcomes and are susceptible to disempowerment and decisional burden when receiving reproductive counseling and considering pregnancy. Nephrologists do not frequently counsel about reproductive health, and no tools exist to support patient-centered reproductive counseling for those with CKD. Methods: A total of 30 patients aged 18 to 45 years with CKD stages 1 to 5 who were assigned female sex at birth and 12 nephrologists from a single academic medical center participated in semistructured qualitative interviews. They were asked about information needs, decision support needs, and facilitators and barriers to reproductive health care and counseling. Thematic analysis was performed. Results: The following 4 main themes were identified: (i) assessing reproductive intentions; (ii) information about reproductive health and kidney disease; (iii) reproductive risk; and (iv) communication and decision-making needs. Patients' reproductive intentions varied over time and shaped the content of information needed from nephrologists. Patients and nephrologists both felt that risk communication could be improved but focused on different aspects to improve the quality of this counseling; nephrologists focused on providing individualized risk estimates and patients focused on balancing risks with benefits and management. Patients desired nephrologists to bring up the topic of reproductive health and counseling in kidney clinic, and this is not frequently or systematically done currently. Conclusion: This work highlights a critical need for more dialog about reproductive health in kidney care, identified differences in what patients and nephrologists think is important in communication and decision-making, and provides an important step in developing patient-centered reproductive counseling tools in nephrology.
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Introduction: Kidney outcomes are improved in primary focal segmental glomerulosclerosis (FSGS) by maintaining a remission in proteinuria. However, characteristics associated with relapses are uncertain. We sought to identify these by analyzing each remission. Methods: We performed a retrospective study in patients with biopsy-proven lesions of FSGS, absent identifiable secondary cause, who had at least 1 remission from nephrotic-range proteinuria. In each patient, we identified every remission, every relapse, and their durations. Using a multilevel logistic regression to account for the clustering of multiple remissions within a patient, we tested which clinical characteristics were independently associated with relapses. Results: In 203 individuals, 312 remissions occurred, 177 with and 135 without relapse. A minority of remissions were atypical, defined by either absent hypoalbuminemia and/or no immunosuppression (IS), in contrast to the classic nephrotic syndrome that remits with IS. Atypical remission variants were just as likely to relapse as the classical presentation. Only 24% of remission events were on maintenance therapy at relapse. Independent characteristics associated with relapses were higher maximal proteinuria while nephrotic; and in remission, higher nadir proteinuria, lower serum albumin, and higher blood pressure. Using these variables, we created a tool estimating the 1-year risk of relapse ranging from 9% to 80%, well-calibrated to the observed data. Conclusion: In FSGS, relapses are frequent but predictable using independent clinical characteristics. We also provide evidence that atypical presentations remit and relapse following the same pattern as classic FSGS presentations. Treatment strategies to prolong remission duration should be addressed in future trials.
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BACKGROUND: There is a lack of randomized controlled trial data regarding differences in immunogenicity of varying coronavirus disease 2019 (COVID-19) mRNA vaccine regimens in CKD populations. METHODS: We conducted a randomized controlled trial at three kidney centers in Toronto, Ontario, Canada, evaluating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response after third dose vaccination. Participants ( n =273) with CKD not on dialysis or receiving dialysis were randomized 1:1 to third dose 30- µ g BNT162b2 (Pfizer-BioNTech) or 100- µ g mRNA-1273 (Moderna). The primary outcome of this study was SARS-CoV-2 IgG-binding antibodies to the receptor-binding domain (anti-RBD). Spike protein (antispike), nucleocapsid protein, and vaccine reactogenicity were also evaluated. Serology was measured before third dose and 1, 3, and 6 months after third dose. A subset of participants ( n =100) were randomly selected to assess viral pseudovirus neutralization against wild-type D614G, B.1.617.2 (Delta), and B.1.1.529 (Omicron BA.1). RESULTS: Among 273 participants randomized, 94% were receiving maintenance dialysis and 59% received BNT162b2 for initial two dose COVID-19 vaccination. Third dose of mRNA-1273 was associated with higher mean anti-RBD levels (1871 binding antibody units [BAU]/ml; 95% confidence interval [CI], 829 to 2988) over a 6-month period in comparison with third dose BNT162b2 (1332 BAU/ml; 95% CI, 367 to 2402) with a difference of 539 BAU/ml (95% CI, 139 to 910; P = 0.009). Neither antispike levels nor neutralizing antibodies to wild-type, Delta, and Omicron BA.1 pseudoviruses were statistically different. COVID-19 infection occurred in 10% of participants: 15 (11%) receiving mRNA-1273 and 11 (8%) receiving BNT162b2. Third dose BNT162b2 was not associated with a significant different risk for COVID-19 in comparison with mRNA-1273 (hazard ratio, 0.78; 95% CI, 0.27 to 2.2; P = 0.63). CONCLUSIONS: In patients with CKD, third dose COVID-19 mRNA vaccination with mRNA-1273 elicited higher SARS-CoV-2 anti-RBD levels in comparison with BNT162b2 over a 6-month period. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: COVID-19 Vaccine Boosters in Patients With CKD (BOOST KIDNEY), NCT05022329 .
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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.
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Vacuna nCoV-2019 mRNA-1273 , Fallo Renal Crónico , Humanos , Vacuna BNT162 , Diálisis Renal , Vacunas contra la COVID-19 , Anticuerpos Neutralizantes , Vacunación , Vacunas Combinadas , Anticuerpos AntiviralesAsunto(s)
Enfermedades Renales , Humanos , Embarazo , Femenino , Enfermedades Renales/diagnóstico , Riñón/patología , BiopsiaRESUMEN
Purpose of Program: Glomerulonephritis (GN) is a group of rare kidney diseases that is increasingly being managed with higher cost immunosuppressive (IS) agents in Canada. Ontario Health's Ontario Renal Network (ORN) oversees the management and delivery of GN services in the province. Stakeholder surveys previously conducted by ORN identified that both clinicians and patients do not perceive access to GN medications as comprehensive or timely. The program conducted a focused jurisdictional scan among 7 provinces to inform ORN initiatives to improve access to GN medications. Specifically, the program examined clinician experience with GN access, public drug coverage criteria, and timelines for public coverage for select IS agents (ie, tacrolimus, cyclosporine, mycophenolate mofetil [MMF], mycophenolate sodium, rituximab, and eculizumab) used to manage GN in adults who live in Canada. Methods: For the selected IS agents, a focused jurisdictional scan on medication access was conducted by ORN in 2018 and updated in July 2022. Information was obtained by searching the gray literature and/or credible online sources for public funding policies and eligibility criteria. Findings were supplemented by personal communications with provincial drug programs and consulting GN clinical experts from 7 provinces (ie, Alberta, British Columbia, Saskatchewan, Manitoba, Ontario, Nova Scotia, and Quebec). Key Findings: Clinicians from different provinces prescribe IS agents similarly for GN indications, despite distinctions in public drug funding policies. While patients can obtain public funding for many IS agents, for GN, most provinces rely on case-by-case review processes. In addition, provinces can vary in their funding criteria and which IS agents are listed on the public formulary. For IS agents that require prior authorization or case-by-case review, timelines vary by province with decisions taking a few days to weeks. British Columbia, with a GN-specific drug formulary, had the most integrated and efficient system for patients and prescribers. Limitations: This scan primarily relied on publicly available information for drug coverage criteria and clinician experience with access in their province. Since this scan was conducted, public drug coverage criteria and/or application processes may have changed. Implications: While patients in most provinces have similar needs and nephrologists similar prescribing patterns, gaps still exist for publicly funded GN medications. Interprovincial differences in the drugs funded, funding criteria, and application process may affect timely and equitable access to GN medications across Canada. Given the rarity of GN, a pan-Canadian funding approach may be warranted to improve the current state.
Objectif du programme: Les glomérulonéphrites (GN) sont un groupe de néphropathies rares qui sont de plus en plus fréquemment traitées avec les agents immunosuppresseurs (IS) coûteux au Canada. Le Réseau rénal de l'Ontario (ORNOntario Renal Network) de Santé Ontario supervise la gestion et la prestation des services liés à la GN dans cette province. Des enquêtes menées précédemment par l'ORN auprès des parties prenantes ont révélé que tant les cliniciens que les patients ne percevaient pas l'accès aux médicaments pour traiter la GN comme complet ou opportun. Le programme a mené une analyse ciblée des territoires de compétences dans sept provinces afin d'orienter les initiatives de l'ORN ayant pour objectif d'améliorer l'accès aux médicaments pour traiter la GN. Plus précisément, le programme a examiné l'expérience des cliniciens en matière d'accès aux médicaments pour traiter la GN, les critères d'admissibilité au régime public d'assurance-médicaments et les délais de couverture publique de certains agents IS (p. ex., tacrolimus, cyclosporine, mycophénolate mofétil [MMF], mycophénolate sodique, Rituximab, éculizumab) utilisés pour traiter la GN chez les adultes canadiens. Méthodologie: Une analyse ciblée des territoires de compétences quant à l'accès aux médicaments a été réalisée par l'ORN en 2018 et mise à jour en juillet 2022. L'information quant aux politiques de financement public et aux critères d'admissibilité a été obtenue en effectuant une recherche dans la littérature grise et des sources crédibles en ligne. Les résultats ont été complétés par des communications directes avec les régimes provinciaux d'assurance-médicaments et des experts cliniques de la GN de sept provinces (Alberta, Colombie-Britannique, Saskatchewan, Manitoba, Ontario, Nouvelle-Écosse et Québec). Principaux résultats: Les cliniciens des différentes provinces prescrivent des agents IS de façon similaire pour les indications liées à la GN, malgré des distinctions dans les politiques publiques de financement des médicaments. Bien que les patients bénéficient d'une couverture publique pour de nombreux agents IS, pour le traitement de la GN, la plupart des provinces s'appuient sur des processus d'examen au cas par cas. De plus, il peut exister des différences entre les provinces en ce qui concerne les critères de financement et les agents IS qui figurent sur leur formulaire public. Dans le cas des agents IS nécessitant une autorisation au préalable ou un examen au cas par cas, les délais varient d'une province à l'autre; les décisions pouvant prendre de quelques jours à quelques semaines. La Colombie-Britannique, qui dispose d'un formulaire de médicaments pour traiter spécifiquement la GN, présente le système le plus intégré et le plus efficace pour les patients et les prescripteurs. Limites: Cette analyse s'est principalement appuyée sur des renseignements accessibles au public en ce qui concerne les critères de couverture des médicaments et l'expérience des cliniciens en matière d'accès dans leur province. Les critères de couverture des médicaments publics et les processus de demande pourraient avoir changé depuis que cette analyse a été effectuée. Conclusion: Bien que les patients de la plupart des provinces aient des besoins similaires et que les néphrologues aient des habitudes de prescription similaires, des lacunes subsistent en ce qui concerne le financement public des médicaments pour traiter la GN. Les différences interprovinciales entre les médicaments financés, les critères de financement et le processus de demande peuvent avoir une incidence sur l'accès opportun et équitable aux médicaments pour traiter la GN à travers le Canada. Étant donné la rareté de cette maladie, une approche de financement pancanadienne pourrait être justifiée afin d'améliorer l'état actuel.
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BACKGROUND: The 2021 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend following anti-phospholipase A2 receptor (PLA2R) antibody levels as a marker of treatment response in membranous nephropathy; however, the optimal timing to evaluate antibody levels and how to combine them with other clinical variables are currently unknown. METHODS: We used a cohort of 85 patients from the Membranous Nephropathy Trial Of Rituximab (MENTOR) with anti-PLA2R antibodies ≥14 RU/ml to identify risk factors for not experiencing proteinuria remission after 12 months of treatment with cyclosporine or rituximab. Three landmark times were considered: at baseline and after 3 and 6 months of treatment. Logistic regression model performance was evaluated using C-statistics and model fit (Akaike information criterion [AIC], R 2 ). RESULTS: The model at baseline that best predicted no remission included anti-PLA2R antibodies >323 RU/ml and creatinine clearance; the best model after 3 months included the change from baseline in both antibody and albumin levels; and the best model after 6 months included antibody levels >14 RU/ml, creatinine clearance, and the change from baseline in albumin. Compared with the model at baseline, the model at 3 months had better model fit (AIC 70.9 versus 96.4, R 2 51.8% versus 30.1%) and higher C-statistic (0.93 versus 0.83, P = 0.008). The model at 6 months had no difference in performance compared with the model at 3 months (AIC 68.6, R 2 53.0%, C-statistic 0.94, P = 0.67). CONCLUSIONS: In patients with membranous nephropathy treated with cyclosporine or rituximab in the MENTOR trial, we found that the optimal method to evaluate risk factors for the probability of treatment response was to use anti-PLA2R antibody levels combined with albumin levels after 3 months of treatment, which was significantly better than using antibody levels alone or risk factor evaluation at baseline, with no added benefit of waiting until 6 months of treatment. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_10_09_CJN0000000000000237.mp3.
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Glomerulonefritis Membranosa , Humanos , Glomerulonefritis Membranosa/tratamiento farmacológico , Rituximab/uso terapéutico , Receptores de Fosfolipasa A2 , Creatinina , Ciclosporina/uso terapéutico , Factores de Riesgo , Albúminas , AutoanticuerposRESUMEN
Introduction: Preeclampsia increases the risk for future chronic kidney disease (CKD). Among those diagnosed with CKD, it is unclear whether a prior history of preeclampsia, or other complications in pregnancy, negatively impact kidney disease progression. In this longitudinal analysis, we assessed kidney disease progression among women with glomerular disease with and without a history of a complicated pregnancy. Methods: Adult women enrolled in the Cure Glomerulonephropathy study (CureGN) were classified based on a history of a complicated pregnancy (defined by presence of worsening kidney function, proteinuria, or blood pressure; or a diagnosis of preeclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelets [HELLP] syndrome), pregnancy without these complications, or no pregnancy history at CureGN enrollment. Linear mixed models were used to assess estimated glomerular filtration rate (eGFR) trajectories and urine protein-to-creatinine ratios (UPCRs) from enrollment. Results: Over a median follow-up period of 36 months, the adjusted decline in eGFR was greater in women with a history of a complicated pregnancy compared to those with uncomplicated or no pregnancies (-1.96 [-2.67, -1.26] vs. -0.80 [-1.19, -0.42] and -0.64 [-1.17, -0.11] ml/min per 1.73 m2 per year, P = 0.007). Proteinuria did not differ significantly over time. Among those with a complicated pregnancy history, eGFR slope did not differ by timing of first complicated pregnancy relative to glomerular disease diagnosis. Conclusions: A history of complicated pregnancy was associated with greater eGFR decline in the years following glomerulonephropathy (GN) diagnosis. A detailed obstetric history may inform counseling regarding disease progression in women with glomerular disease. Continued research is necessary to better understand pathophysiologic mechanisms by which complicated pregnancies contribute to glomerular disease progression.
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Background: People living with chronic kidney disease (CKD) have been disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic, including higher rates of infection, hospitalization, and death. Data on responsiveness to COVID-19 vaccination strategies and immunogenicity are limited, yet required to inform vaccination strategies in this at-risk population. Objective: The objective of this study is to characterize the longitudinal serologic response to COVID-19 vaccination. Design: This is a prospective observational cohort study. Setting: Participating outpatient kidney programs within Ontario and British Columbia. Patients: Up to 2500 participants with CKD G3b-5D receiving COVID-19 vaccination, including participants receiving dialysis and kidney transplant recipients (CKD G1T-5T). Measurements: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies (anti-spike, anti-receptor binding domain, anti-nucleocapsid) will be detected by ELISA (enzyme-linked immunosorbent assay) from serum or dried blood spot testing. In a subset of participants, neutralizing antibodies against novel variants of concern will be evaluated. Peripheral blood mononuclear cells will be collected for exploratory immune profiling of SARS-CoV-2 specific cellular immunity. Methods: Participants will be recruited prior to or following any COVID-19 vaccine dose and have blood sampled for serological testing at multiple timepoints: 1, 3, 6, 9, and 12 months post vaccination. When possible, samples will be collected prior to a dose or booster. Participants will remain in the study for at least 1 year following their last COVID-19 vaccine dose. Strengths and limitations: The adaptive design of this study allows for planned modification based on emerging evidence or rapid changes in public health policy surrounding vaccination. Limitations include incomplete earlier timepoints for blood collection due to rapid vaccination of the population. Conclusions: This large multicenter serologic study of participants living with kidney disease will generate data on the kinetics of SARS-CoV-2 immune response to vaccination across the spectrum of CKD, providing insights into the amplitude and duration of immunity conferred by COVID-19 vaccination and allowing for characterization of factors associated with immune response. The results of this study may be used to inform immunization guidelines and public health recommendations for the 4 million Canadians living with CKD.
Contexte: Les personnes atteintes d'insuffisance rénale chronique (IRC) ont été touchées de façon disproportionnée par la pandémie de COVID-19 ayant notamment présenté des taux plus élevés d'infection, d'hospitalisation et de décès. Les données sur la réactivité aux stratégies de vaccination de la COVID-19 et à l'immunogénicité sont limitées, mais elles sont nécessaires pour développer des stratégies de vaccination dans cette population à risque. Objectif: Caractériser la réponse sérologique longitudinale à la vaccination contre la COVID-19. Conception: Étude de cohorte observationnelle prospective. Cadre: Les programmes ambulatoires de santé rénale participants en Ontario et en Colombie-Britannique. Sujets: Jusqu'à 2 500 personnes atteintes d'IRC G3B-5D recevant un vaccin contre la COVID-19, y compris des patients suivant des traitements de dialyse et des receveurs d'une greffe rénale (IRC G1T-5T). Mesures: Les anticorps IgG anti-SARS-CoV-2 (anti-spike, anti-domaine de liaison au récepteur, anti-nucléocapside) seront détectés par ELISA à partir du sérum ou de taches de sang séché. Un sous-groupe de sujets participera également à l'évaluation d'anticorps neutralisants dirigés contre les nouveaux variants préoccupants. Des cellules mononuclées de sang périphérique seront prélevées pour établir un profil immunitaire exploratoire de l'immunité cellulaire spécifique au SARS-CoV-2. Méthodologie: Les sujets seront recrutés avant ou après toute dose du vaccin contre la COVID-19 et se soumettront à des prélèvements sanguins pour les tests sérologiques à 1, 3, 6, 9 et 12 mois post-vaccination. Lorsque possible, des échantillons seront prélevés avant l'administration d'une dose ou d'un rappel. Les sujets demeureront dans l'étude pendant au moins un an après leur dernière dose de vaccin contre la COVID-19. Points forts et limites: La conception adaptative de l'étude permet d'apporter des modifications planifiées fondées sur de nouvelles données ou des changements rapides dans les politiques de santé publique entourant la vaccination. Les résultats sont limités par l'absence de certains prélèvements sanguins antérieurs (point temporels) en raison de la vaccination rapide de la population. Conclusion: Cette vaste étude sérologique multicentrique menée auprès de personnes atteintes de néphropathie fournira des données sur la cinétique de la réponse immunitaire à la vaccination contre le SARS-CoV-2 dans l'ensemble du spectre de l'IRC. Elle fournira des informations sur l'amplitude et la durée de l'immunité conférée par la vaccination contre la COVID-19 et permettra de caractériser les facteurs associés à la réponse immunitaire. Ces résultats serviront à orienter les recommandations de santé publique et les lignes directrices en matière d'immunisation pour les quatre millions de Canadiens et Canadiennes qui vivent avec l'IRC.
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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.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Vacunas contra la COVID-19/efectos adversos , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Retrospectivos , SARS-CoV-2 , Ontario/epidemiología , ARN Mensajero , Diálisis RenalRESUMEN
BACKGROUND: People with advanced CKD are at high risk of mortality and morbidity from coronavirus disease 2019 (COVID-19). We measured rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe outcomes in a large population attending advanced CKD clinics during the first 21 months of the pandemic. We examined risk factors for infection and case fatality, and we assessed vaccine effectiveness in this population. METHODS: In this retrospective cohort study, we analyzed data on demographics, diagnosed SARS-CoV-2 infection rates, outcomes, and associated risk factors, including vaccine effectiveness, for people attending a province-wide network of advanced CKD clinics during the first four waves of the pandemic in Ontario, Canada. RESULTS: In a population of 20,235 patients with advanced CKD, 607 were diagnosed with SARS-CoV-2 infection over 21 months. The case fatality rate at 30 days was 19% overall but declined from 29% in the first wave to 14% in the fourth. Hospitalization and intensive care unit (ICU) admission rates were 41% and 12%, respectively, and 4% started long-term dialysis within 90 days. Significant risk factors for diagnosed infection on multivariable analysis included lower eGFR, higher Charlson Comorbidity Index, attending advanced CKD clinics for more than 2 years, non-White ethnicity, lower income, living in the Greater Toronto Area, and long-term care home residency. Being doubly vaccinated was associated with lower 30-day case fatality rate (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.03 to 0.52). Older age (OR, 1.06 per year; 95% CI, 1.04 to 1.08) and higher Charlson Comorbidity Index (OR, 1.11 per unit; 95% CI, 1.01 to 1.23) were associated with higher 30-day case fatality rate. CONCLUSIONS: People attending advanced CKD clinics and diagnosed with SARS-CoV-2 infection in the first 21 months of the pandemic had high case fatality and hospitalization rates. Fatality rates were significantly lower in those who were doubly vaccinated. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_04_10_CJN10560922.mp3.
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COVID-19 , Insuficiencia Renal Crónica , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Estudios Retrospectivos , Estudios de Cohortes , Eficacia de las Vacunas , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Ontario/epidemiologíaRESUMEN
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.
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Complicaciones del Embarazo , Nacimiento Prematuro , Insuficiencia Renal Crónica , Femenino , Humanos , Recién Nacido , Embarazo , Estudios de Cohortes , Ontario/epidemiología , Complicaciones del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/etiología , Proteinuria , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Estudios Retrospectivos , Tasa de Filtración GlomerularRESUMEN
The diagnosis of nephrotic syndrome relies on clinical presentation and descriptive patterns of injury on kidney biopsies, but not specific to underlying pathobiology. Consequently, there are variable rates of progression and response to therapy within diagnoses. Here, an unbiased transcriptomic-driven approach was used to identify molecular pathways which are shared by subgroups of patients with either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Kidney tissue transcriptomic profile-based clustering identified three patient subgroups with shared molecular signatures across independent, North American, European, and African cohorts. One subgroup had significantly greater disease progression (Hazard Ratio 5.2) which persisted after adjusting for diagnosis and clinical measures (Hazard Ratio 3.8). Inclusion in this subgroup was retained even when clustering was limited to those with less than 25% interstitial fibrosis. The molecular profile of this subgroup was largely consistent with tumor necrosis factor (TNF) pathway activation. Two TNF pathway urine markers were identified, tissue inhibitor of metalloproteinases-1 (TIMP-1) and monocyte chemoattractant protein-1 (MCP-1), that could be used to predict an individual's TNF pathway activation score. Kidney organoids and single-nucleus RNA-sequencing of participant kidney biopsies, validated TNF-dependent increases in pathway activation score, transcript and protein levels of TIMP-1 and MCP-1, in resident kidney cells. Thus, molecular profiling identified a subgroup of patients with either MCD or FSGS who shared kidney TNF pathway activation and poor outcomes. A clinical trial testing targeted therapies in patients selected using urinary markers of TNF pathway activation is ongoing.