Potassium reduction with sodium zirconium cyclosilicate in patients with heart failure.

AIMS: Several patients with heart failure and reduced ejection fraction (HFrEF) do not receive renin-angiotensin-aldosterone system (RAAS) inhibitors at the recommended dose or at all, frequently due to actual or feared hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is an orally administered non-absorbed intestinal potassium binder proven to lower serum potassium concentrations. METHODS AND RESULTS: PRIORITIZE-HF was an international, multicentre, parallel-group, randomized, double-blind, placebo-controlled study to evaluate the benefits and risks of using SZC to intensify RAAS inhibitor therapy. Patients with symptomatic HFrEF were eligible and randomly assigned to receive SZC 5 g or placebo once daily for 12 weeks. Doses of study medication and RAAS inhibitors were titrated during the treatment period. The primary endpoint was the proportion of patients at 12 weeks in the following categories: (i) any RAAS inhibitor at less than target dose, and no MRA; (ii) any RAAS inhibitor at target dose and no MRA; (ii) MRA at less than target dose; and (iv) MRA at target dose. Due to challenges in participant management related to the COVID-19 pandemic, the study was prematurely terminated with 182 randomized patients. There was no statistically significant difference in the distribution of patients by RAAS inhibitor treatment categories at 3 months (P = 0.43). The proportion of patients at target MRA dose was numerically higher in the SZC group (56.4%) compared with the placebo group (47.0%). Overall, SZC was well tolerated. CONCLUSIONS: PRIORITIZE-HF was terminated prematurely due to COVID-19 and did not demonstrate a statistically significant increase in the intensity of RAAS inhibitor therapies with the potassium-reducing agent SZC compared with placebo.

SARS-CoV-2 Infection during the Omicron Surge among Patients Receiving Dialysis: The Role of Circulating Receptor-Binding Domain Antibodies and Vaccine Doses.

BACKGROUND: It is unclear whether circulating antibody levels conferred protection against SARS-CoV-2 infection among patients receiving dialysis during the Omicron-dominant period. METHODS: We followed monthly semiquantitative SARS-CoV-2 RBD IgG index values in a randomly selected nationwide cohort of patients receiving dialysis and ascertained SARS-CoV-2 infection during the Omicron-dominant period of December 25, 2021 to January 31, 2022 using electronic health records. We estimated the relative risk for documented SARS-CoV-2 infection by vaccination status and by circulating RBD IgG using a log-binomial model accounting for age, sex, and prior COVID-19. RESULTS: Among 3576 patients receiving dialysis, 901 (25%) received a third mRNA vaccine dose as of December 24, 2021. Early antibody responses to third doses were robust (median peak index IgG value at assay limit of 150). During the Omicron-dominant period, SARS-CoV-2 infection was documented in 340 (7%) patients. Risk for infection was higher among patients without vaccination and with one to two doses (RR, 2.1; 95% CI, 1.6 to 2.8, and RR, 1.3; 95% CI, 1.0 to 1.8 versus three doses, respectively). Irrespective of the number of vaccine doses, risk for infection was higher among patients with circulating RBD IgG <23 (506 BAU/ml) (RR range, 2.1 to 3.2, 95% CI, 1.3 to 3.4 and 95% CI, 2.2 to 4.5, respectively) compared with RBD IgG ≥23. CONCLUSIONS: Among patients receiving dialysis, a third mRNA vaccine dose enhanced protection against SARS-CoV-2 infection during the Omicron-dominant period, but a low circulating RBD antibody response was associated with risk for infection independent of the number of vaccine doses. Measuring circulating antibody levels in this high-risk group could inform optimal timing of vaccination and other measures to reduce risk of SARS-CoV-2 infection.

SARS-CoV-2 Neutralizing Monoclonal Antibodies for the Treatment of COVID-19 in Kidney Transplant Recipients.

Background: Morbidity and mortality associated with coronavirus disease 2019 (COVID-19) infection in kidney transplant recipients are high and early outpatient interventions to prevent progression to severe disease are needed. SARS-CoV-2 neutralizing mAbs, including bamlanivimab and casirivimab-imdevimab, received emergency use authorization in the United States in November 2020 for treatment of mild to moderate COVID-19 disease. Methods: We performed a retrospective analysis of 27 kidney transplant recipients diagnosed with COVID-19 between July 2020 and February 2021 who were treated with bamlanivimab or casirivimab-imdevimab and immunosuppression reduction. We additionally identified 13 kidney transplant recipients with COVID-19 who had mild to moderate disease at presentation, who did not receive mAbs, and had SARS-CoV-2 serology testing available. Results: There were no deaths or graft failures in either group. Both infusions were well tolerated. Four of the 27 patients treated with mAbs required hospitalization due to COVID-19. Four of 13 patients who did not receive mAbs required hospitalization due to COVID-19. Patients who received mAbs demonstrated measurable anti-SARS-CoV-2 IgG with angiotensin-converting enzyme 2 (ACE2) receptor blocking activity at the highest level detectable at 90 days postinfusion, whereas ACE2 blocking activity acquired from natural immunity in the mAb-untreated group was weak. Conclusions: Bamlanivimab and casirivimab-imdevimab combined with immunosuppression reduction were well tolerated and associated with favorable clinical outcomes in kidney transplant recipients diagnosed with mild to moderate COVID-19.

SARS-CoV-2 Vaccine Antibody Response and Breakthrough Infection in Patients Receiving Dialysis.

BACKGROUND: Whether breakthrough SARS-CoV-2 infections after vaccination are related to the level of postvaccine circulating antibody is unclear. OBJECTIVE: To determine longitudinal antibody-based response and risk for breakthrough infection after SARS-CoV-2 vaccination. DESIGN: Prospective study. SETTING: Nationwide sample from dialysis facilities. PATIENTS: 4791 patients receiving dialysis. MEASUREMENTS: Remainder plasma from a laboratory processing routine monthly tests was used to measure qualitative and semiquantitative antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. To evaluate whether peak or prebreakthrough RBD values were associated with breakthrough infection, a nested case-control analysis matched each breakthrough case patient to 5 control patients by age, sex, and vaccination month and adjusted for diabetes status and region of residence. RESULTS: Of the 4791 patients followed with monthly RBD assays, 2563 were vaccinated as of 14 September 2021. Among the vaccinated patients, the estimated proportion with an undetectable RBD response increased from 6.6% (95% CI, 5.5% to 7.8%) 14 to 30 days after vaccination to 20.2% (CI, 17.0% to 23.3%) 5 to 6 months after vaccination. Estimated median index values decreased from 91.9 (CI, 78.6 to 105.2) 14 to 30 days after vaccination to 8.4 (CI, 7.6 to 9.3) 5 to 6 months after vaccination. Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days before breakthrough infection. Compared with prebreakthrough index RBD values of 23 or higher (equivalent to ≥506 binding antibody units per milliliter), prebreakthrough RBD values less than 10 and values from 10 to less than 23 were associated with higher odds for breakthrough infection (rate ratios, 11.6 [CI, 3.4 to 39.5] and 6.0 [CI, 1.5 to 23.6], respectively). LIMITATIONS: Single measure of vaccine response; ascertainment of COVID-19 diagnosis from electronic health records. CONCLUSION: The antibody response to SARS-CoV-2 vaccination wanes rapidly in persons receiving dialysis. In this population, the circulating antibody response is associated with risk for breakthrough infection. PRIMARY FUNDING SOURCE: Ascend Clinical Laboratory.

Serial SARS-CoV-2 Receptor-Binding Domain Antibody Responses in Patients Receiving Dialysis.

BACKGROUND: Assessing the evolution of SARS-CoV-2 immune response among patients receiving dialysis can define its durability in a highly clinically relevant context because patients receiving dialysis share the characteristics of persons most susceptible to SARS-CoV-2 infection. OBJECTIVE: To evaluate the persistence of SARS-CoV-2 receptor-binding domain (RBD) IgG in seroprevalent patients receiving dialysis. DESIGN: Prospective. SETTING: Nationwide sample from dialysis facilities. PATIENTS: 2215 patients receiving dialysis who had evidence of SARS-CoV-2 infection as of July 2020. MEASUREMENTS: Remainder plasma from routine monthly laboratories was used to measure semiquantitative RBD IgG index value over 6 months. RESULTS: A total of 2063 (93%) seroprevalent patients reached an assay detectable response (IgG index value ≥1). Most (n = 1323, 60%) had responses in July with index values classified as high (IgG ≥10); 1003 (76%) remained within this stratum. Adjusted median index values declined slowly but continuously (July vs. December values were 21 vs. 13; P < 0.001). The trajectory of the response did not vary by age group, sex, race/ethnicity, or diabetes status. Patients without an assay detectable response (n = 137) were more likely to be White and in the younger (18 to 44 years) or older (≥80 years) age groups and less likely to have diabetes and hypoalbuminemia. LIMITATION: Lack of data on symptoms or reverse transcriptase polymerase chain reaction diagnosis, cohort of persons who survived infection, and use of a semiquantitative assay. CONCLUSION: Despite impaired immunity, most seropositive patients receiving dialysis maintained RBD antibody levels over 6 months. A slow and continual decline in median antibody levels over time was seen, but no indication that subgroups with impaired immunity had a shorter-lived humoral response was found. PRIMARY FUNDING SOURCE: Ascend Clinical Laboratories.

SARS-CoV-2 Vaccine Acceptability in Patients on Hemodialysis: A Nationwide Survey.

BACKGROUND: Patients on dialysis are at increased risk for COVID-19-related complications. However, a substantial fraction of patients on dialysis belong to groups more likely to be hesitant about vaccination. METHODS: With the goal of identifying strategies to increase COVID-19 vaccine uptake among patients on hemodialysis, we conducted a nationwide vaccine acceptability survey, partnering with a dialysis network to distribute an anonymized English and Spanish language online survey in 150 randomly selected facilities in the United States. We used logistic regression to evaluate characteristics of vaccine-hesitant persons. RESULTS: A total of 1515 (14% of eligible) patients responded; 20% of all responders, 29% of patients aged 18-44 years, and 29% of Black responders reported being hesitant to seek the COVID-19 vaccine, even if the vaccine was considered safe for the general population. Odds of vaccine hesitancy were higher among patients aged 18-44 years versus those 45-64 years (odds ratio [OR], 1.5; 95% confidence interval [95% CI], 1.0 to 2.3), Black patients versus non-Hispanic White patients (OR, 1.9; 95% CI, 1.3 to 2.7), Native Americans or Pacific Islanders versus non-Hispanic White patients (OR, 2.0; 95% CI, 1.1 to 3.7), and women versus men (OR, 1.6; 95% CI, 1.2 to 2.0). About half (53%) of patients who were vaccine hesitant expressed concerns about side effects. Responders' main information sources about COVID-19 vaccines were television news and dialysis staff (68% and 38%, respectively). CONCLUSIONS: A substantial proportion of patients receiving in-center hemodialysis in the United States are hesitant about seeking COVID-19 vaccination. Facilitating uptake requires outreach to younger patients, women, and Black, Native American, or Pacific Islander patients, and addressing concerns about side effects.

Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA: a cross-sectional study.

BACKGROUND: Many patients receiving dialysis in the USA share the socioeconomic characteristics of underserved communities, and undergo routine monthly laboratory testing, facilitating a practical, unbiased, and repeatable assessment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence. METHODS: For this cross-sectional study, in partnership with a central laboratory that receives samples from approximately 1300 dialysis facilities across the USA, we tested the remainder plasma of 28 503 randomly selected adult patients receiving dialysis in July, 2020, using a spike protein receptor binding domain total antibody chemiluminescence assay (100% sensitivity, 99·8% specificity). We extracted data on age, sex, race and ethnicity, and residence and facility ZIP codes from the anonymised electronic health records, linking patient-level residence data with cumulative and daily cases and deaths per 100 000 population and with nasal swab test positivity rates. We standardised prevalence estimates according to the overall US dialysis and adult population, and present estimates for four prespecified strata (age, sex, region, and race and ethnicity). FINDINGS: The sampled population had similar age, sex, and race and ethnicity distribution to the US dialysis population, with a higher proportion of older people, men, and people living in majority Black and Hispanic neighbourhoods than in the US adult population. Seroprevalence of SARS-CoV-2 was 8·0% (95% CI 7·7-8·4) in the sample, 8·3% (8·0-8·6) when standardised to the US dialysis population, and 9·3% (8·8-9·9) when standardised to the US adult population. When standardised to the US dialysis population, seroprevalence ranged from 3·5% (3·1-3·9) in the west to 27·2% (25·9-28·5) in the northeast. Comparing seroprevalent and case counts per 100 000 population, we found that 9·2% (8·7-9·8) of seropositive patients were diagnosed. When compared with other measures of SARS-CoV-2 spread, seroprevalence correlated best with deaths per 100 000 population (Spearman's ρ=0·77). Residents of non-Hispanic Black and Hispanic neighbourhoods experienced higher odds of seropositivity (odds ratio 3·9 [95% CI 3·4-4·6] and 2·3 [1·9-2·6], respectively) compared with residents of predominantly non-Hispanic white neighbourhoods. Residents of neighbourhoods in the highest population density quintile experienced increased odds of seropositivity (10·3 [8·7-12·2]) compared with residents of the lowest density quintile. County mobility restrictions that reduced workplace visits by at least 5% in early March, 2020, were associated with lower odds of seropositivity in July, 2020 (0·4 [0·3-0·5]) when compared with a reduction of less than 5%. INTERPRETATION: During the first wave of the COVID-19 pandemic, fewer than 10% of the US adult population formed antibodies against SARS-CoV-2, and fewer than 10% of those with antibodies were diagnosed. Public health efforts to limit SARS-CoV-2 spread need to especially target racial and ethnic minority and densely populated communities. FUNDING: Ascend Clinical Laboratories.

Estimated SARS-CoV-2 Seroprevalence in US Patients Receiving Dialysis 1 Year After the Beginning of the COVID-19 Pandemic.

Importance: Seroprevalence studies complement data on detected cases and attributed deaths in assessing the cumulative spread of the SARS-CoV-2 virus. Objective: To estimate seroprevalence of SARS-CoV-2 antibodies in patients receiving dialysis and adults in the US in January 2021 before the widespread introduction of COVID-19 vaccines. Design, Setting, and Participants: This cross-sectional study used data from the third largest US dialysis organization (US Renal Care), which has facilities located nationwide, to estimate SARS-CoV-2 seroprevalence among US patients receiving dialysis. Remainder plasma (ie, plasma that would have otherwise been discarded) of all patients receiving dialysis at US Renal Care facilities from January 1 to 31, 2021, was tested for SARS-CoV-2 antibodies. Patients were excluded if they had a documented dose of SARS-CoV-2 vaccination or if a residence zip code was missing from electronic medical records. Crude seroprevalence estimates from this sample (January 2021) were standardized to the US adult population using the 2018 American Community Survey 1-year estimates and stratified by age group, sex, self-reported race/ethnicity, neighborhood race/ethnicity composition, neighborhood income level, and urban or rural status. These data and case detection rates were then compared with data from a July 2020 subsample of patients who received dialysis at the same facilities. Exposures: Age, sex, race/ethnicity, and region of residence as well as neighborhood race/ethnicity composition, poverty, population density, and urban or rural status. Main Outcomes and Measures: The spike protein receptor-binding domain total antibody assay (Siemens Healthineers; manufacturer-reported sensitivity of 100% and specificity of 99.8%) was used to estimate crude SARS-CoV-2 seroprevalence in the unweighted sample, and then the estimated seroprevalence rates for the US dialysis and adult populations were calculated, adjusting for age, sex, and region. Results: A total of 21 464 patients (mean [SD] age, 63.1 [14.2] years; 12 265 men [57%]) were included in the unweighted sample from January 2021. The patients were disproportionately older (aged 65-79 years, 7847 [37%]; aged ≥80 years, 2668 [12%]) and members of racial/ethnic minority groups (Hispanic patients, 2945 [18%]; non-Hispanic Black patients, 4875 [29%]). Seroprevalence of SARS-CoV-2 antibodies was 18.9% (95% CI, 18.3%-19.5%) in the sample, with a seroprevalence of 18.7% (95% CI, 18.1%-19.2%) standardized to the US dialysis population, and 21.3% (95% CI, 20.3%-22.3%) standardized to the US adult population. In the unweighted sample, younger persons (aged 18-44 years, 25.9%; 95% CI, 24.1%-27.8%), those who self-identified as Hispanic or living in Hispanic neighborhoods (25.1%; 95% CI, 23.6%-26.4%), and those living in the lowest-income neighborhoods (24.8%; 95% CI, 23.2%-26.5%) were among the subgroups with the highest seroprevalence. Little variability was observed in seroprevalence by geographic region, population density, and urban or rural status in the January 2021 sample (largest regional difference, 1.2 [95% CI, 1.1-1.3] higher odds of seroprevalence in residents of the Northeast vs West). Conclusions and Relevance: In this cross-sectional study of patients receiving dialysis in the US, fewer than 1 in 4 patients had evidence of SARS-CoV-2 antibodies 1 year after the first case of SARS-CoV-2 infection was detected in the US. Results standardized to the US population indicate similar prevalence of antibodies among US adults. Vaccine introduction to younger individuals, those living in neighborhoods with a large population of racial/ethnic minority residents, and those living in low-income neighborhoods may be critical to disrupting the spread of infection.

Laboratory correlates of SARS-CoV-2 seropositivity in a nationwide sample of patients on dialysis in the U.S.

Patients on dialysis are at high risk for death due to COVID-19, yet a significant proportion do survive as evidenced by presence of SARS-CoV-2 antibodies in 8% of patients in the U.S. in July 2020. It is unclear whether patients with seropositivity represent the subgroup with robust health status, who would be more likely to mount a durable antibody response. Using data from a July 2020 sample of 28,503 patients receiving dialysis, we evaluated the cross-sectional association of SARS-CoV-2 seropositivity with laboratory surrogates of patient health. In separate logistic regression models, we assessed the association of SARS-CoV-2 seropositivity with seven laboratory-based covariates (albumin, creatinine, hemoglobin, sodium, potassium, phosphate, and parathyroid hormone), across the entire range of the laboratory and in comparison to a referent value. Models accounted for age, sex, region, race and ethnicity, and county-level COVID-19 deaths per 100,000. Odds of seropositivity for albumin 3 and 3.5 g/dL were 2.1 (95% CI 1.9-2.3) and 1.3 (1.2-1.4) respectively, compared with 4 g/dL. Odds of seropositivity for serum creatinine 5 and 8 mg/dL were 1.8 (1.6-2.0) and 1.3 (1.2-1.4) respectively, compared with 12.5 mg/dL. Lower values of hemoglobin, sodium, potassium, phosphate, and parathyroid hormone were associated with higher odds of seropositivity. Laboratory values associated with poorer health status and higher risk for mortality were also associated with higher likelihood of SARS-CoV-2 antibodies in patients receiving dialysis.