Use of incremental peritoneal dialysis: impact on clinical outcomes and quality of life measure.

BACKGROUND: Incremental peritoneal dialysis (PD) can be defined as a PD prescription that is less than the standard, full dose prescription and is typically used for patients initiating PD with residual kidney function. It has been suggested that use of incremental peritoneal dialysis may help preserve residual kidney function and may offer better quality of life due to the lower treatment burden, however published evidence is limited. In this study we assessed the associations between incremental peritoneal dialysis use and both clinical outcomes and quality of life measures in a large cohort of incident peritoneal dialysis patients in the US. METHODS: We considered adult patients initiating peritoneal dialysis between 31 July, 2015 and 31 May, 2019 within a single dialysis organization. Patients with body weight < 40 kg, amputation, or an estimated glomerular filtration rate > 20 mL/min during the first 4 weeks on peritoneal dialysis were excluded. Patients were assigned to exposure groups based on peritoneal dialysis prescription during dialysis weeks 5-8. Incremental peritoneal dialysis was defined by treatment frequency, number of exchanges/day, and exchange volume (for continuous ambulatory peritoneal dialysis patients) or by treatment frequency and presence/absence of last fill (for automated peritoneal dialysis patients). Analyses were performed separately for continuous ambulatory peritoneal dialysis and automated peritoneal dialysis. For each analysis, incremental peritoneal dialysis patients were propensity score matched to eligible full-dose peritoneal dialysis patients. Patients were followed for a maximum of 12 months until censoring for loss to follow-up or study end. Outcomes were compared using Poisson models (mortality, hospitalization, peritoneal dialysis discontinuation), linear mixed models (estimated glomerular filtration rate), and paired t tests (KDQOL domain scores). RESULTS: Among continuous ambulatory peritoneal dialysis patients, compared to full-dose peritoneal dialysis, incremental peritoneal dialysis use was associated with better KDQOL scores on 3 domains: physical composite score (42.5 vs 37.7, p = 0.03), burden of kidney disease (60.2 vs 45.6, p = 0.003), effects of kidney disease (79.4 vs 72.3, p = 0.05). Hospitalization and mortality rates were numerically lower (0.77 vs 1.12 admits/pt-year, p = 0.09 and 5.0 vs 10.2 deaths/100 pt-years, p = 0.22), while no associations were found with estimated glomerular filtration rate or peritoneal dialysis discontinuation rate. Use of incremental peritoneal dialysis was not associated with any discernable effects on outcomes in automated peritoneal dialysis patients. CONCLUSION: These results suggest that there may be benefits of using incremental PD in the context of continuous ambulatory peritoneal dialysis, particularly with respect to quality of life as a prescription strategy when initiating peritoneal dialysis. While no significant benefits of incremental peritoneal dialysis were detected among patients initiating automated peritoneal dialysis, no detrimental effects of using incremental schedules were observed for either peritoneal dialysis type.

Comparative Effectiveness of mRNA-based BNT162b2 Vaccine versus Adenovirus Vector-Based Ad26.COV2.S Vaccine for the Prevention of COVID-19 among Dialysis Patients.

BACKGROUND: Studies have demonstrated that mRNA-based SARS-CoV-2 vaccines are highly effective among patients on dialysis. Because individual vaccines may be differentially available or acceptable to patients, it is important to understand comparative effectiveness relative to other vaccines, such those on the basis of adenovirus technologies. METHODS: In this retrospective study, we compared the clinical effectiveness of adenovirus vector-based Ad26.COV2.S (Janssen/Johnson & Johnson) to mRNA-based BNT162b2 (Pfizer/BioNTech) in a contemporary cohort of patients on dialysis. Patients who received a first BNT162b2 dose were matched 1:1 to Ad26.COV2.S recipients on the basis of date of first vaccine receipt, US state of residence, site of dialysis care (in-center versus home), history of COVID-19, and propensity score. The primary outcome was the comparative rate of COVID-19 diagnoses starting in the 7th week postvaccination. In a subset of consented patients who received Ad26.COV2.S, blood samples were collected ≥28 days after vaccination and anti-SARS-CoV-2 immunoglobulin G antibodies were measured. RESULTS: A total of 2572 matched pairs of patients qualified for analysis. Cumulative incidence rates of COVID-19 did not differ for BNT162b2 versus Ad26.COV2.S. No differences were observed in peri-COVID-19 hospitalizations and deaths among patients receiving BNT162b2 versus Ad26.COV2.S, who were diagnosed with COVID-19 during the at-risk period. Results were similar when excluding patients with a history of COVID-19, in subgroup analyses restricted to patients who completed the two-dose BNT162b2 regimen, and in patients receiving in-center hemodialysis. SARS-CoV-2 antibodies were detected in 59.4% of 244 patients who received Ad26.COV2.S. CONCLUSIONS: In a large real-world cohort of patients on dialysis, no difference was detected in clinical effectiveness of BNT162b2 and Ad26.COV2.S over the first 6 months postvaccination, despite an inconsistent antibody response to the latter.

Antibody Status, Disease History, and Incidence of SARS-CoV-2 Infection Among Patients on Chronic Dialysis.

BACKGROUND: Although reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rare among individuals with few coronavirus disease 2019 (COVID-19) risk factors, the ability of naturally acquired immunity to prevent reinfection among patients with ESKD is not known. METHODS: This prospective study was conducted among adults with ESKD treated with in-center hemodialysis (ICHD) in the United States. Exposure was ascribed on the basis of the presence or absence of IgG against SARS-CoV-2 at baseline, and separately, a history of documented COVID-19 before study entry. Outcomes were assessed after an infection-free period, and were any SARS-CoV-2 infection (i.e., detected by protocolized PCR tests or during routine clinical surveillance), and clinically manifest COVID-19 (consisting of only the latter). RESULTS: Of 2337 consented participants who met study inclusion criteria, 9.5% were anti-SARS-CoV-2 IgG positive at baseline; 3.6% had a history of COVID-19. Over 6679 patient-months of follow-up, 263 participants had evidence of any SARS-CoV-2 infection, including 141 who had clinically manifest COVID-19. Presence of anti-SARS-CoV-2 IgG (versus its absence) at baseline was associated with lower risk of any SARS-CoV-2 infection (incidence rate ratio, 0.55; 95% confidence interval, 0.32 to 0.95) and clinically manifest COVID-19 0.21 (95% confidence interval, 0.07 to 0.67). CONCLUSION: Among patients with ESKD, naturally acquired anti-SARS-CoV-2 IgG positivity is associated with a 45% lower risk of subsequent SARS-CoV-2 infection, and a 79% lower risk of clinically manifest COVID-19. Because natural immunity is incomplete, patients with ESKD should be prioritized for SARS-CoV-2 vaccination, independent of their COVID-19 disease history.

SARS-CoV-2 Antibody Seroprevalence Among Maintenance Dialysis Patients in the United States.

RATIONALE & OBJECTIVE: Reported coronavirus disease 2019 (COVID-19) cases underestimate the actual number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Patients receiving maintenance dialysis are at high risk for COVID-19 and higher case rates have been reported relative to the general population. To better understand infection patterns, we performed a seroprevalence study among maintenance dialysis patients at a large dialysis organization in the United States. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: We measured immunoglobulin G antibodies in an institutional review board-approved study of remnant serum samples collected for routine laboratory screenings in a national sample of 12,932 maintenance dialysis patients (May 27 to July 1, 2020). EXPOSURE: State, sex, age, and race. OUTCOMES: Seropositivity; ratio of seropositivity to known COVID-19 case rate. ANALYTIC APPROACH: Seropositivity was calculated overall and by state, sex, age, and race. The ratio of seropositivity to known COVID-19 cases was calculated overall and by state. RESULTS: 747 (5.8%) samples were seropositive. Seroprevalence varied by state and was lowest in Kentucky (1.0%) and highest in New York (23.6%). Seroprevalence was similar among men and women. Among samples from patients younger than 70 years, 6.0% to 6.5% were seropositive; whereas 5.2% and 3.9% of samples from patients aged 70 to 79 and 80 years or older, respectively, were seropositive. Samples from Black and Hispanic patients were 7.3% and 7.7% positive, respectively, compared with 2.8% of samples from White patients. After adjustment, risk differences among racial groups were lower but not eliminated. During the study period, the known COVID-19 case rate was 3.3%. The ratio of seropositivity to known COVID-19 cases was 1.7. LIMITATIONS: Imperfect assay sensitivity; results represent infections occurring before July 2020; deidentification prevented comparison of antibodies to previous COVID-19 status for individual patients; may not generalize to patients dialyzing with other providers or in other countries. CONCLUSIONS: Seroprevalence was 5.8% among dialysis patients as of July 1, 2020. This indicates that the actual number of infections was 1.7 times greater than reported cases. This ratio is lower than reported in the general population, suggesting that there were fewer unknown infections among maintenance dialysis patients.

Safety and efficacy of heparin during dialysis in the context of systemic anticoagulant and antiplatelet medications.

Heparin is widely used to prevent coagulation during hemodialysis. Although systemic anticoagulants and antiplatelet agents are commonly prescribed in the hemodialysis population, the safety and efficacy of heparin in the presence of these medications is unclear. This retrospective cohort study considered adult hemodialysis patients treated in the United States (August 2015-July 2017). For each month, patients were ascribed a three-part exposure status (heparin use, anticoagulant use, antiplatelet agent use) based on electronic health records. Outcomes included anemia measures, peri-treatment bleeding and clotting, and hospitalization for gastrointestinal (GI) bleeding. Within systemic medication exposure categories, associations of heparin use were examined using adjusted generalized linear, negative binomial, or Poisson models. Across all systemic medication exposures, heparin use was associated with lower erythropoiesis stimulating agent (ESA) dose, higher hemoglobin levels, and lower monthly intravenous (IV) iron dose; lower rates of clotting during treatment and hospitalization for GI bleeding; and similar rates of peri-treatment bleeding. Associations with respect to ESA, IV iron, hemoglobin, and clotting were approximately twofold more potent in the absence of a systemic anticoagulant; the presence of an antiplatelet agent had little impact. Neither medication type influenced associations between heparin use and peri-treatment or GI bleeding. These results suggest that heparin use is safe and effective in the presence and absence of systemic anticoagulants and antiplatelet agents. Clinical judgment must be applied to assess bleeding risk in individual patients; however, the decision to withhold heparin should not solely be based upon the concurrent use of anticoagulant or antiplatet agents.

The Impact of Midodrine on Outcomes in Patients with Intradialytic Hypotension.

BACKGROUND: Intradialytic hypotension (IDH) is a frequent complication of hemodialysis, and is associated with significant morbidity and mortality. Off-label use of the alpha-1 andrenergic receptor agonist midodrine to reduce the frequency and severity of IDH is common. However, limited data exist to support this practice. This study sought to examine real-world efficacy of midodrine with respect to relevant clinical and hemodynamic outcomes. METHODS: Here, we compared a variety of clinical and hemodynamic outcomes among adult patients who were prescribed midodrine (n = 1,046) and matched controls (n = 2,037), all of whom were receiving in-center hemodialysis treatment at dialysis facilities in the United States (July 2015 - September 2016). Mortality, all-cause hospitalization, cardiovascular hospitalization, and hemodynamic outcomes were considered from the month following the initiation of midodrine (or corresponding month for controls) until censoring for discontinuation of dialysis, transplant, loss to follow-up, or study end (September 30, 2016). Rate outcomes were compared using Poisson models and quantitative outcomes using linear mixed models; all models were adjusted for imbalanced patient characteristics. RESULTS: Compared to non-use, midodrine use was associated with higher rates of death (adjusted incidence rate ratio 1.37, 95% CI 1.15-1.62), all-cause hospitalization (1.31, 1.19-1.43) and cardiovascular hospitalization (1.41, 1.17-1.71). During follow-up, midodrine use tended to be associated with lower pre-dialysis systolic blood pressure (SBP), lower nadir SBP, greater fall in SBP during dialysis, and a greater proportion of treatments affected by IDH. CONCLUSION: Although residual confounding may have influenced the results, the associations observed here are not consistent with a potent beneficial effect of midodrine with respect to either clinical or hemodynamic outcomes.