Serial SARS-CoV-2 Antibody Titers in Vaccinated Dialysis Patients: Prevalence of Unrecognized Infection and Duration of Seroresponse.

Rationale & Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are likely underdiagnosed, but the degree of underdiagnosis among patients receiving maintenance dialysis is unknown. The durability of the immune response after the third vaccine dose in this population also remains uncertain. This descriptive study tracked antibody levels to (1) assess the rate of undiagnosed infections and (2) characterize seroresponse durability after the third dose. Study Design: Retrospective observational study. Setting & Participants: SARS-CoV-2-vaccinated patients receiving maintenance dialysis through a national dialysis provider. Immunoglobulin G spike antibodies [anti-spike immunoglobulin (Ig) G] titers were assessed monthly after vaccination. Exposures: Two and 3 doses of SARS-CoV-2 vaccine. Outcomes: Undiagnosed and diagnosed SARS-CoV-2 infections; anti-spike IgG titers over time. Analytical Approach: Undiagnosed SARS-CoV-2 infections were identified as an increase in anti-spike IgG titer of ≥100 BAU/mL, not associated with receipt of vaccine or diagnosed SARS-CoV-2 infection (by polymerase chain reaction test or antigen test). In descriptive analyses, anti-spike IgG titers were followed over time. Results: Among 2,703 patients without previous coronavirus disease 2019 (COVID-19) who received an initial 2-dose vaccine series, 271 had diagnosed SARS-CoV-2 infections (3.4 per 10,000 patient-days) and 129 had undiagnosed SARS-CoV-2 infections (1.6 per 10,000 patient-days). Among 1,894 patients without previous COVID-19 who received a third vaccine dose, 316 had diagnosed SARS-CoV-2 infections (7.0 per 10,000 patient-days) and 173 had undiagnosed SARS-CoV-2 infections (3.8 per 10,000 patient-days). In both cohorts, anti-spike IgG levels declined over time. Of the initial 2-dose cohort, 66% had a titer of ≥500 BAU/mL in the first month, with 24% maintaining a titer of ≥500 BAU/mL at 6 months. Of the third dose cohort, 95% had a titer of ≥500 BAU/mL in the first month after the third dose, with 77% maintaining a titer of ≥500 BAU/mL at 6 months. Limitations: The assays used had upper limits. Conclusions: Among patients receiving maintenance dialysis, about 1 in every 3 SARS-CoV-2 infections was undiagnosed. Given this population's vulnerability to COVID-19, ongoing infection control measures are needed. A 3-dose primary mRNA vaccine series optimizes seroresponse rate and durability. Plain-Language Summary: Patients receiving maintenance dialysis have been particularly vulnerable to COVID-19. Using serially measured antibodies, we found that a substantial proportion (about one-third) of SARS-CoV-2 infections among this population had been missed, both among those who had completed a 2-dose vaccine series and among those who had received a third vaccine dose. Such missed infections likely had only mild or minimal symptoms, but this failure to recognize all infections is concerning. Furthermore, vaccines have been effective among patients receiving dialysis, but our study additionally shows that the immune response wanes over time, even after a third dose. There is therefore a role for ongoing vigilance against this highly transmissible infection.

Serial SARS-CoV-2 antibody titers in vaccinated dialysis patients: prevalence of unrecognized infection and duration of seroresponse.

Rationale & Objective: SARS-CoV-2 infections are likely underdiagnosed, but the degree of underdiagnosis among maintenance dialysis patients is unknown. Durability of the immune response after third vaccine doses in this population also remains uncertain. This study tracked antibody levels to 1) assess the rate of undiagnosed infections and 2) characterize seroresponse durability after third doses. Study Design: Retrospective observational study. Setting & Participants: SARS-CoV-2 vaccinated patients receiving maintenance dialysis through a national dialysis provider. Immunoglobulin G spike antibodies (anti-spike IgG) titers were assessed monthly following vaccination. Exposures: Two and three doses of SARS-CoV-2 vaccine. Outcomes: Undiagnosed and diagnosed SARS-CoV-2 infections; anti-spike IgG titers over time. Analytical Approach: "Undiagnosed" SARS-CoV-2 infections were identified as an increase in anti-spike IgG titer of ≥ 100 BAU/mL, not associated with receipt of vaccine or "diagnosed" SARS-CoV-2 infection (by PCR or antigen test). In descriptive analyses, anti-spike IgG titers were followed over time. Results: Among 2660 patients without prior COVID-19 who received an initial two-dose vaccine series, 371 (76%) SARS-CoV-2 infections were diagnosed and 115 (24%) were undiagnosed. Among 1717 patients without prior COVID-19 who received a third vaccine dose, 155 (80%) SARS-CoV-2 infections were diagnosed and 39 (20%) were undiagnosed. In both cohorts, anti-spike IgG levels declined over time. Of the initial two-dose cohort, 66% had a titer ≥ 500 BAU/mL in the first month, with 23% maintaining a titer ≥ 500 BAU/mL at six months. Of the third dose cohort, 95% had a titer ≥ 500 BAU/mL in the first month after the third dose, with 76% maintaining a titer ≥ 500 BAU/mL at six months. Limitations: Assays used had upper limits. Conclusions: Among maintenance dialysis patients, 20-24% of SARS-CoV-2 infections were undiagnosed. Given this population's vulnerability to COVID-19, ongoing infection control measures are needed. A three-dose primary mRNA vaccine series optimizes seroresponse rate and durability.

A real world comparison of HepB (Engerix-B®) and HepB-CpG (Heplisav-B®) vaccine seroprotection in patients receiving maintenance dialysis.

BACKGROUND: Vaccination against hepatitis B virus (HBV) is recommended for dialysis patients. Two reports comparing seroprotection (SP) rates following HepB and HepB-CpG in vaccine-naïve patients with chronic kidney disease enrolled few dialysis patients (n = 122 combined). SP rates in a subset of dialysis patients were not reported or not powered to detect statistically significant differences. SP rates in those requiring additional vaccine series or booster doses are not known. METHODS: A retrospective cohort analysis including dialysis patients completing HepB or HepB-CpG vaccination between January 2019 and December 2020. Vaccine-naïve patients received a series of HepB or HepB-CpG (Series 1). A repeat series was given to nonresponders (Series 2). A booster regimen consists of one dose of either vaccine. Primary outcome was achieving SP (anti-HBs >10 mIU/mL) at least 60 days after the last HBV vaccine dose for Series 1 and Series 2, and achieving SP at least 3 weeks post-booster. RESULTS: For Series 1 (n = 3509), SP after HepB vaccination was significantly higher (62.9% versus 50.1% for HepB-CpG; P < 0.0001). Series 2 (n = 1040) and booster (n = 2028) SP rates were similar between vaccines. Patients that received up to four HepB-CpG doses had higher SP rates compared with four doses of HepB (82.0% versus 62.9%, respectively; P < 0.0001). CONCLUSIONS: SP rates in hepatitis B vaccine-naïve dialysis patients administered a recommended four doses of HepB were higher than those recommended two doses of HepB-CpG. SP rates were higher and achieved sooner if HepB-CpG was utilized initially and, if needed, for Series 2. Optimal HepB-CpG dosing deserves further study.

Seroresponse to SARS-CoV-2 Vaccines among Maintenance Dialysis Patients over 6 Months.

BACKGROUND AND OBJECTIVES: Although most patients receiving maintenance dialysis exhibit initial seroresponse to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, concerns exist regarding the durability of this antibody response. This study evaluated seroresponse over time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included patients on maintenance dialysis, from a midsize national dialysis provider, who received a complete SARS-CoV-2 vaccine series and had at least one antibody titer checked after full vaccination. IgG spike antibodies (anti-spike IgG) titers were assessed monthly with routine laboratory tests after vaccination; the semiquantitative assay reported a range between zero and ≥20 Index. Descriptive analyses compared trends over time by history of coronavirus disease 2019 (COVID-19) and vaccine type. Time-to-event analyses examined the outcome of loss of seroresponse (anti-spike IgG <1 Index or development of COVID-19). Cox regression adjusted for additional clinical characteristics. RESULTS: Among 1870 patients receiving maintenance dialysis, 1569 had no prior COVID-19. Patients without prior COVID-19 had declining titers over time. Among 443 recipients of BNT162b2 (Pfizer), median (interquartile range) anti-spike IgG titer declined from ≥20 (5.89 to ≥20) in month 1 after full vaccination to 1.96 (0.60-5.88) by month 6. Among 778 recipients of mRNA-1273 (Moderna), anti-spike IgG titer declined from ≥20 (interquartile range, ≥20 to ≥20) in month 1 to 7.99 (2.61 to ≥20) by month 6. The 348 recipients of Ad26.COV2.S (Janssen) had a lower titer response than recipients of an mRNA vaccine over all time periods. In time-to-event analyses, recipients of Ad26.COV2.S and mRNA-1273 had the shortest and longest time to loss of seroresponse, respectively. The maximum titer reached in the first 2 months after full vaccination was associated with durability of the anti-spike IgG seroresponse; patients with anti-spike IgG titer 1-19.99 had a shorter time to loss of seroresponse compared with patients with anti-spike IgG titer ≥20 (hazard ratio, 15.5; 95% confidence interval, 11.7 to 20.7). CONCLUSIONS: Among patients receiving maintenance dialysis, vaccine-induced seroresponse wanes over time across vaccine types. Early titers after full vaccination are associated with the durability of seroresponse.

Oral intradialytic nutritional supplement use and mortality in hemodialysis patients.

BACKGROUND: Hemodialysis patients have high mortality rates, potentially reflecting underlying comorbid conditions and ongoing catabolism. Intradialytic oral nutritional supplements may reduce this risk. STUDY DESIGN: Retrospective propensity-matched cohort. SETTING & PARTICIPANTS: Maintenance hemodialysis patients treated at Dialysis Clinic Inc facilities who were initiated on a nutritional supplement protocol in September to October 2010 were matched using a propensity score to patients at facilities at which the protocol was not used. PREDICTORS: Prescription of the protocol, whereby hemodialysis patients with serum albumin levels ≤3.5g/dL would initiate oral protein supplementation during the dialysis procedure. Sensitivity analyses matched on actual supplement intake during the first 3 study months. Covariates included patient and facility characteristics, which were used to develop the propensity scores and adjust multivariable models. OUTCOMES: All-cause mortality, ascertained though March 2012. RESULTS: Of 6,453 eligible patients in 101 eligible hemodialysis facilities, the protocol was prescribed to 2,700, and 1,278 of these were propensity matched to controls. Mean age was 61 ± 15 (SD) years and median dialysis vintage was 34 months. There were 258 deaths among protocol assignees versus 310 among matched controls during a mean follow-up of 14 months. In matched analyses, protocol prescription was associated with a 29% reduction in the hazard of all-cause mortality (HR, 0.71; 95% CI, 0.58-0.86); adjustment had minimal impact on models. In time-dependent models incorporating change in albumin level, protocol status remained significant but was attenuated in models incorporating a 30-day lag. Similar results were seen in sensitivity analyses of 439 patients receiving supplements who were propensity-matched to controls, with 116 deaths among supplement users versus 140 among controls (HR, 0.79; 95% CI, 0.60-1.05), achieving statistical significance in adjusted models. LIMITATIONS: Observational design, potential residual confounding. CONCLUSIONS: Prescription of an oral nutritional supplement protocol and use of oral protein nutritional supplements during hemodialysis are associated with reduced mortality among in-center maintenance hemodialysis patients, an effect likely not mediated by change in serum albumin levels.

Computerized decision support for EPO dosing in hemodialysis patients.

BACKGROUND: Anemia management in hemodialysis patients poses significant challenges. The present study explored the hypothesis that computerized dosing of intravenous erythropoietin (EPO) would increase the percentage of hemoglobin (Hb) values within the target range and reduce staff time spent on anemia management. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: In-center hemodialysis patients who received EPO at Dialysis Clinic Inc dialysis units for at least 3 months between October 1, 2005, and April 30, 2006. QUALITY IMPROVEMENT PLAN: Computerized decision support (CDS) for EPO dosing is compared with manual physician-directed dosing. OUTCOMES: Achieved monthly Hb values, quantity of EPO administered, and time spent by dialysis unit personnel. MEASUREMENTS: Monthly Hb and quantity of EPO administered to 1,118 patients from 18 dialysis units treated using CDS and 7,823 patients from 125 dialysis units treated using manual dosing. RESULTS: There was no difference in the likelihood of a monthly Hb level of 11-12 or 10-12 g/dL using CDS compared with manual dosing. The likelihood of an Hb level > 12 g/dL decreased and the likelihood of an Hb level < 10 g/dL increased using CDS. EPO use was 4% lower using CDS, although the difference was not statistically significant. CDS was associated with a nearly 50% decrease (P < 0.001) in the time spent by dialysis unit staff on anemia management. LIMITATIONS: Retrospective and nonrandomized. CONCLUSION: The number of monthly Hb values in an 11- (and 10-) to 12-g/dL target range and EPO use did not differ with EPO dosing using CDS compared with manual dosing. Staff resources devoted to anemia management decreased significantly using CDS.

Reducing versus discontinuing erythropoietin at high hemoglobin levels.

A 2006 change in Medicare policy allowed reimbursement for erythropoietin (EPO) in dialysis patients whose most recent hemoglobin exceeded 13 g/dl. We investigated the effects of a change in dosing algorithm implemented in response to this policy, in which EPO dosages were reduced instead of temporarily discontinued for hemoglobin levels > or =13 g/dl. Among 1688 individuals in 18 hemodialysis units, the reduction protocol resulted in more hemoglobin levels > or =13 g/dl (P < 0.0001), fewer levels between 11 and 12.9 g/dl (P < or = 0.004), no difference in the proportion of levels <11 g/dl, and more EPO administered per session (P < 0.0001) than the discontinuation protocol. In view of the expense of erythropoiesis stimulating agents and the uncertainty of the safety of using EPO to achieve high hemoglobin targets, this study suggests that discontinuation, rather than reduction, of EPO treatment is appropriate when hemoglobin reaches 13 g/dl in hemodialysis patients.

Developing decision support for dialysis treatment of chronic kidney failure.

The complexity, variability, quantitative nature, and data density of treatment for chronic kidney failure make dialysis information systems excellent candidates for computerized decision support. We describe the development of an intelligent system building on existing knowledge and susceptible to reconfiguration on the basis of knowledge acquired during the use of the system. Various decision support techniques were used to design and develop the decision support modules. This paper briefly reviews the literature on clinical decision support, discusses some of the problems faced by practitioners in managing chronic kidney failure (end-stage renal disease) patients, and sets forth the decision support techniques used in developing a dialysis decision support system.