Immunogenicity of SARS-CoV-2 Vaccine in Dialysis.

BACKGROUND: Patients receiving maintenance dialysis represent a high-risk, immune-compromised population with 15%-25% COVID-19 mortality rate who were unrepresented in clinical trials of mRNA vaccines. METHODS: All patients receiving maintenance dialysis who received two doses of SARS-CoV-2 mRNA vaccines with antibody test results drawn ≥14 days after the second dose, as documented in the electronic health record through March 18, 2021, were included. Response was on the basis of levels of Ig-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike-antigen (seropositive ≥2 U/L) using an FDA-approved semiquantitative chemiluminescent assay (ADVIA Centaur XP/XPT COV2G). RESULTS: Among 186 patients on dialysis from 30 clinics in eight states tested 23±8 days after receiving two vaccine doses, there were 165 (88.7%) responders with 70% at maximum titer. There was no significant difference between BNT162b2/Pfizer (148 out of 168, 88.1%) and mRNA-1273/Moderna (17 out of 18, 94.4%), P=0.42. All 38 patients with COVID-19 history were responders, with 97% at maximum titer. Among patients without COVID-19, 127 out of 148 (85.8%) were responders, comparable between BNT162b2/Pfizer (113 out of 133) and mRNA-1273/Moderna (14 out of 15) vaccines (85.0% versus 93.3%, P=0.38). CONCLUSIONS: Most patients receiving maintenance dialysis responded after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine, suggesting the short-term development of antispike antibody is good, giving hope that most of these patients who are vulnerable, once immunized, will be protected from COVID-19. Longer-term evaluation is needed to determine antibody titer durability and if booster dose(s) are warranted. Further research to evaluate the approach to patients without a serologic response is needed, including benefits of additional dose(s) or administration of alternate options.

Regional and Temporal Variations in Comorbidity Among US Dialysis Patients: A Longitudinal Study of Medicare Claims Data.

Medicare claims data are commonly used to query comorbidities for case-mix adjustment in research of patients with end-stage renal disease (ESRD) in the United States. These adjustments may affect reimbursement and quality rating through comparative profiling and ranking of dialysis facilities. We studied regional and temporal variations in comorbidity from claims data in the United States Renal Data System. Patients with a previous 1-year Medicare history who initiated dialysis therapy between 2006 and 2009 were examined with a follow-up period until 2012. By linking pre- and post-ESRD Medicare claims with the Dartmouth Atlas, we carried out a longitudinal data analysis with multivariable adjustment to investigate regional and temporal variations in the Liu comorbidity index. We identified 23 336 incident hemodialysis patients who were covered by Medicare the year prior to dialysis initiation and had survived with complete 3 years of follow-up data. With the United States divided into 4 geographic regions, the Western region was found to have the lowest Liu index over all 3 follow-up years, compared with the respective years in the other regions (Midwest, Northeast, and South). In comparison with the first year, the Liu index dropped significantly during the second and third years of follow-up across all 4 regions. Significant regional and temporal variations observed in the comorbidity index cannot be explained by differences in reimbursement (average per state) or predialysis comorbidity. Based on our exploratory study, future studies should focus on identifying the factors and reasons for these variations which have the potential to affect health care policy and research.

Successful Hemodialysis Arteriovenous Fistula Creation in a Patient With Continuous-Flow Left Ventricular Assist Device Support.

Heart failure necessitating left ventricular assist device (LVAD) support can lead to kidney failure requiring dialysis. Some of these patients may require long-term hemodialysis (HD). Optimal vascular access for a patient on long-term HD therapy with an LVAD remains a complex issue. The majority of LVADs are of the continuous-flow type, and it has been theorized that native arteriovenous fistula maturation may be impaired in a setting of decreased pulsatile arterial flow. We describe a case of successful creation and use of an arteriovenous fistula in an HD-dependent patient with a continuous-flow LVAD.

Assessing the Adequacy of Small Solute Clearance for Various Dialysis Modalities, with Inclusion of Residual Native Kidney Function.

Measurement of small molecule clearance remains important in the clinical care of patients requiring long-term dialysis. Many patients maintain a significant degree of residual native kidney function and may have nontraditional schedules with or without combined dialysis modalities. In this review, we examine and outline methods for comparing small molecule clearances among various dialysis prescriptions and modalities, with inclusion of residual kidney urea clearance.

Removal of dabigatran by hemodialysis.

Dabigatran is a newly available oral direct thrombin inhibitor approved for anticoagulation therapy to prevent strokes in patients with nonvalvular atrial fibrillation. Unlike warfarin, dabigatran's observed therapeutic window and minimal drug-to-drug interaction suggest that invasive laboratory testing and dose adjustment is not necessary. In circumstances of excessive anticoagulation, such as overdoses, decreased kidney function, or instances of significant bleeding, reversing dabigatran's effects may be necessary. Unlike warfarin, no rapid-acting antidote to reverse the effects of dabigatran is known. However, hemodialysis has been suggested as a method of removing dabigatran and thereby reducing its anticoagulant effect. We describe a case in which hemodialysis was used in an attempt to remove dabigatran in a patient with excessive anticoagulation from dabigatran and severe intracranial hemorrhage. Serial dabigatran levels suggested that hemodialysis removed the drug. However, given the large volume of distribution of dabigatran in the terminal phase of elimination, a rebound in drug level was noted. We suggest that a longer duration of therapy or more continuous modality of hemodialysis may be needed in conjunction with the initial hemodialysis treatment of dabigatran coagulopathy.

Immunogenicity of SARS-CoV-2 Vaccine in Dialysis.

BACKGROUND: Patients receiving maintenance dialysis represent a high risk, immune-compromised population with 15-25% COVID mortality rate who were unrepresented in clinical trials evaluated for mRNA vaccines' emergency use authorization. METHOD: All patients receiving maintenance dialysis that received two doses of SARS-CoV-2 mRNA vaccines with antibody test results drawn ≥14 days after the second dose, as documented in the electronic health record through March 18, 2021 were included. We report seroresponse based on levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen (seropositive ≥2) using FDA-approved semi-quantitative chemiluminescent assay (ADVIA Centaur® XP/XPT COV2G). RESULTS: Among 186 dialysis patients from 32 clinics in 8 states tested 23±8 days after receiving 2 vaccine doses, mean age was 68±12 years, with 47% women, 21% Black, 26% residents in long-term care facilities and 97% undergoing in-center hemodialysis. Overall seropositive rate was 165/186 (88.7%) with 70% at maximum titer and with no significant difference in seropositivity between BNT162b2/Pfizer (N=148) and mRNA-1273/Moderna (N=18) vaccines (88.1% vs. 94.4%, p=0.42). Among patients with COVID-19 history, seropositive rate was 38/38 (100%) with 97% at maximum titer. CONCLUSION: Most patients receiving maintenance dialysis were seropositive after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. Early evidence suggests that vaccinated dialysis patients with prior COVID-19 develop robust antibody response. These results support an equitable and aggressive vaccination strategy for eligible dialysis patients, regardless of age, sex, race, ethnicity, or disability, to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population. SIGNIFICANCE: In this retrospective observational evaluation of SARS-CoV-2 mRNA vaccine response defined by detectable levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen of ≥2 in serum of patients receiving maintenance dialysis, 165/186 (88.7%) were found to be seropositive (with 70% at maximum titer) at least 14 days after completing the second dose. No significant differences were observed by race or other subgroup or by vaccine manufacturer. Therefore, an equitable and aggressive vaccination strategy for all eligible maintenance dialysis patients, regardless of age, sex, race, ethnicity, or disability, is warranted to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population.

Assessing the Impacts of Misclassified Case-Mix Factors on Health Care Provider Profiling: Performance of Dialysis Facilities.

Quantitative metrics are used to develop profiles of health care institutions, including hospitals, nursing homes, and dialysis clinics. These profiles serve as measures of quality of care, which are used to compare institutions and determine reimbursement, as a part of a national effort led by the Center for Medicare and Medicaid Services in the United States. However, there is some concern about how misclassification in case-mix factors, which are typically accounted for in profiling, impacts results. We evaluated the potential effect of misclassification on profiling results, using 20 744 patients from 2740 dialysis facilities in the US Renal Data System. In this case study, we compared 30-day readmission as the profiling outcome measure, using comorbidity data from either the Center for Medicare and Medicaid Services Medical Evidence Report (error-prone) or Medicare claims (more accurate). Although the regression coefficient of the error-prone covariate demonstrated notable bias in simulation, the outcome measure-standardized readmission ratio-and profiling results were quite robust; for example, correlation coefficient of 0.99 in standardized readmission ratio estimates. Thus, we conclude that misclassification on case-mix did not meaningfully impact overall profiling results. We also identified both extreme degree of case-mix factor misclassification and magnitude of between-provider variability as 2 factors that can potentially exert enough influence on profile status to move a clinic from one performance category to another (eg, normal to worse performer).

Evolution of hemodialysis access resistance: a longitudinal 5-year model using functional principal components analysis.

PURPOSE: Arteriovenous fistulae (AVF) and grafts (AVG) are the preferred accesses in hemodialysis (HD). By monitoring access resistance (AR) one can potentially identify problems with an established HD access, but little is known about how these changes in AR occur, or the variations between the two access types as they mature longitudinally. We postulated that AR evolves differentially between AVF and AVG, a critical aspect to further understanding of the natural history of HD accesses. To describe these changes, we applied a novel statistical methodology of functional principal component (FPC) analysis. METHODS: Using ultrasound dilution flow studies, we retrospectively studied 479 functional HD accesses in which a total of 4573 assessments were made. Accounting for patient factors of age, race, gender and diabetes mellitus (DM) status, we employed a multivariate, mixed-effects model. Using the mean effects of those covariates, we then applied FPC analyses to assess the longitudinal, timedependent changes between AVFs and AVGs over a 5-year period. RESULTS: Both types of upper-arm access were associated with a lower initial AR. Older age and DM were associated with a higher AR. Longitudinal AR varied significantly for both AVF and AVG, between the upper arm and lower arm. As a function of time, AVG was associated with an increasing AR. Conversely, AVF, especially upper-arm ones, demonstrated a longitudinal drop in AR. CONCLUSIONS: Evolutionally, AR can be predicted not only by the type of access, but also by the location along the arm of that access and by clinical patient factors. Longitudinal change in AR does differ between AVG and AVF. Our report provides the foundation of observed changes over time and provides insight as to how these variations are affected. We endorse ongoing surveillance to screen for clinical sequelae, even years from initial placement.

Estimating Residual Native Kidney Urea Clearance in Hemodialysis Patients with and without 24-Hour Urine Volume.

RATIONALE AND OBJECTIVE: Quantification of residual native kidney function (RKF) is rarely performed in patients on hemodialysis. Methods of estimating residual kidney urea clearance (KRU) that use commonly available laboratory and clinical data, with or without urine volume information, may be useful tools. STUDY DESIGN: Retrospective, predictive modeling and model validation. SETTING AND PARTICIPANTS: Initial timed urine collections in 604 incident in-center hemodialysis patients on thrice weekly treatments from a single academic center where KRU is measured in usual care. PREDICTORS: Models using combination of serum creatinine and urea, age, weight, height, gender, race, fluid weight gains, and with and without 24-hour urine volume. OUTCOMES: Residual kidney urea clearance. ANALYTIC APPROACH: Generalized linear model was used for model development for KRU using the first urine collection in 604 patients, as both a continuous and binary outcome (for >2.5 mL/min). Model validation was done by bootstrap resampling of the development cohort and with 1093 follow-up measurements. RESULTS: Urine volume alone was the strongest predictor of KRU. The model that included 24-hour urine volume with common clinical data had a high diagnostic accuracy for KRU >2.5 mL/min (area under the curve 0.91 in both development and bootstrap validation) and R2 of 0.56 with outcome as a continuous KRU value. Our model that did not use urine volume performed less well (e.g., AUC 0.75). Analyses of follow-up urine collections in these same subjects yielded comparable or improved performance. LIMITATIONS: Data were retrospective from a single center, no external validation, not validated in 2 or 4 times weekly hemodialysis patients. CONCLUSIONS: Estimation equations for residual kidney urea clearance that use commonly available data in dialysis clinics, with and without urine volume, may be useful tools for evaluation of hemodialysis patients who still have RKF for individualization of dialysis prescriptions.

Data concordance between ESRD Medical Evidence Report and Medicare claims: is there any improvement?

BACKGROUND: Medicare is one of the world's largest health insurance programs. It provides health insurance to nearly 44 million beneficiaries whose entitlements are based on age, disability, or end-stage renal disease (ESRD). Data of these ESRD beneficiaries are collected in the US Renal Data System (USRDS), which includes comorbidity information entered at the time of dialysis initiation (medical evidence data), and are used to shape health care policy. One limitation of USRDS data is the lack of validation of these medical evidence comorbidities against other comorbidity data sources, such as medical claims data. METHODS: We examined the potential for discordance between USRDS Medical Evidence and medical claims data for 11 comorbid conditions amongst Medicare beneficiaries in 2011-2013 via sensitivity, specificity, kappa and hierarchical logistic regression. RESULTS: Among 61,280 patients, most comorbid conditions recorded on the Medical Evidence forms showed high specificity (>0.9), compared to prior medical claims as reference standard. However, both sensitivity and kappa statistics varied greatly and tended to be low (most <0.5). Only diabetes appeared accurate, whereas tobacco use and drug dependence showed the poorest quality (sensitivity and kappa <0.1). Institutionalization and patient region of residency were associated with data discordance for six and five comorbidities out of 11, respectively, after conservative adjustment of multiple testing. Discordance appeared to be non-informative for congestive heart failure but was most varied for drug dependence. CONCLUSIONS: We conclude that there is no improvement in comorbidity data quality in incident ESRD patients over the last two decades. Since these data are used in case-mix adjustment for outcome and quality of care metrics, the findings in this study should press regulators to implement measures to improve the accuracy of comorbidity data collection.

Feasibility of Incremental 2-Times Weekly Hemodialysis in Incident Patients With Residual Kidney Function.

INTRODUCTION: We hypothesized that at least half of incident hemodialysis (HD) patients on 3-times weekly dialysis could safely start on an incremental, 2-times weekly HD schedule if residual kidney function (RKF) had been considered. METHODS: RKF is assessed in all our HD patients. This single-center, retrospective cohort study of incident adult HD patients, who survived ≥6 months on a 3-times weekly HD regimen and had a timed urine collection within 3 months of starting HD, assessed each patient's theoretical ability to achieve adequate urea clearance, ultrafiltration rate, and hemodynamic stability if on 2-times weekly HD. RESULTS: Of the 410 patients in the cohort, we found that 112 (27%) could have optimally and 107 (26%) could have been appropriately considered for 2-times weekly incremental HD. In general, diuretics were underutilized in >50% of subjects who had adequate RKF urea clearance. The optimal 2-times weekly patients had better potassium and phosphorus control. The correlation coefficient of calculated residual kidney urea clearance with 24-hour urine volume and with kinetic model residual kidney clearance was 0.68 and 0.99, respectively. DISCUSSION: More than 50% of incident HD patients with RKF have adequate kidney urea clearance to be considered for 2-times weekly HD. When additionally ultrafiltration volume and blood pressure stability are taken into account, more than one-fourth of the total cohort could optimally start HD in an incremental fashion.

Area-level poverty, race/ethnicity & dialysis star ratings.

The Centers for Medicare and Medicaid Services recently released a five star rating system as part of 'Dialysis Facility Compare' to help patients identify and choose high performing clinics in the US. Eight dialysis-related measures determine ratings. Little is known about the association between surrounding community sociodemographic characteristics and star ratings. Using data from the U.S. Census and over 6000 dialysis clinics across the country, we examined the association between dialysis clinic star ratings and characteristics of the local population: 1) proportion of population below the federal poverty level (FPL); 2) proportion of black individuals; and 3) proportion of Hispanic individuals, by correlation and regression analyses. Secondary analyses with Quality Incentive Program (QIP) scores and population characteristics were also performed. We observed a negligible correlation between star ratings and the proportion of local individuals below FPL; Spearman coefficient, R = -0.09 (p<0.0001), and a stronger correlation between star ratings and the proportion of black individuals; R = -0.21 (p<0.0001). Ordered logistic regression analyses yielded adjusted odds ratio of 0.91 (95% confidence interval [0.80-1.30], p = 0.12) and 0.55 ([0.48-0.63], p<0.0001) for high vs. low level of proportion below FPL and proportion of black individuals, respectively. In contrast, a near-zero correlation was observed between star ratings and the proportion of Hispanic individuals. Correlations varied substantially by country region, clinic profit status and clinic size. Analyses using clinic QIP scores provided similar results. Sociodemographic characteristics of the surrounding community, factors typically outside of providers' direct control, have varying levels of association with clinic dialysis star ratings.

Treatment of tunneled dialysis catheter malfunction: revision versus exchange.

INTRODUCTION: Exchange procedures involve tunneled dialysis catheter (TDC) removal and exchange over a wire, using the same exit site and venotomy site. Diagnostic imaging or intervention was generally not performed in exchange procedures. Revision procedures involve placement of new TDC using the previous venotomy site and a new tunnel and exit site. The majority of revisions usually include diagnostic imaging and intervention in the central circulation if needed. METHODS: A retrospective single review of 70 patients who underwent 97 TDC replacements from 2010 to early 2012 because of catheter malfunction was evaluated for either infection or malfunction within 30 days of the procedure. RESULTS: There were 41 exchanges and 56 revisions out of the 97 procedures performed. There were eight infections (documented by positive blood culture) in the exchanges (19.5%) and one in the revision group (1.8%). The need for an additional procedure due to malfunction was 10 in the exchange (24.4%) and 10 (17.8%) in the revision group. CONCLUSIONS: Revision is a clearly superior procedure with regard to infection and more data need to be gathered as to whether it will decrease repeat procedures.

Late acceleration of glomerular filtration rate decline is a risk for hemodialysis catheter use in patients with established nephrology chronic kidney disease care.

Chronic kidney disease (CKD) patients with established nephrology care have a high rate of tunneled dialysis catheters (TDC) as first vascular access when transitioning to hemodialysis (HD). We sought to identify factors associated with this problem. Patients who started HD and had prior CKD care within our renal clinic were categorized according to access type at incident HD. Clinical factors, all estimated glomerular filtration rates (eGFR), renal clinic attendance records, hospital admissions in the 6 months preceding HD start, and patient participation in predialysis education course were analyzed. Three hundred thirty-eight patients initiated HD, 107 received pre-HD CKD care within our clinics. Seventy patients started with a TDC. All groups started HD at similar eGFR values. The trajectory of eGFR decline in the 6 months prior to HD start was significantly more rapid in the TDC group. Patients in the TDC group had more acute health events in the prior 6 months. Multivariate modeling showed that failure to attend a predialysis education course and having a more rapid rate of eGFR decline in the 6 months prior to dialysis initiation were both associated with TDC use. Patients with CKD nephrology care who initiated HD with a TDC as first vascular access had a more rapid rate of decline in eGFR in the months preceding dialysis start and were less likely to have attended our predialysis education course. This appears to correspond with the observed increased number of emergency and hospital visits in the 6 months prior to end-stage renal disease.

Intra-access blood flow in patients with newly created upper-arm arteriovenous native fistulae for hemodialysis access.

BACKGROUND: The upper-arm native arteriovenous fistula for hemodialysis (HD) vascular access is an important option in the long-term HD population. This single-center cohort study evaluated intra-access blood flow (Q AC) in 3 variants of newly created upper-arm fistulae. METHODS: Fifty-three patients with mature, working, upper-arm fistulae composed of brachial artery to cephalic vein (n = 27), brachial artery to basilic vein (n = 13), and brachial artery to median antecubital vein (n = 13) fistulae were included. Nine of 13 brachio-median antecubital fistulae were of the Gracz type and used the deep perforating vein. Q AC was measured by means of ultrasound velocity dilution during HD. In brachio-median antecubital fistulae, additional flow in the alternate draining vein was measured by means of duplex ultrasound, with 9 of 11 studied patients showing a patent alternate outflow, of whom 7 patients showed substantial flow (median, 0.7 L/min). RESULTS: Q AC in the HD-used primary vein in brachio-median antecubital fistulae (0.85 L/min) was significantly less than those of brachiocephalic and brachiobasilic fistulae (1.4 and 1.7 L/min, respectively). However, when the additional flow provided by the patent alternate vein in brachio-median antecubital fistulae was considered, flow rates provided by all 3 variants of fistulae appeared similar. The inverse correlation between alternate-vein and primary-vein flows (r = -0.70; P = 0.017) suggested there was competitive flow between the 2 venous outlets. There was no instance of access recirculation. CONCLUSION: Upper-arm fistulae, regardless of type, provide excellent blood flows and should be considered routinely if a wrist fistula is not feasible. The patent alternate vein in the brachio-median antecubital or Gracz fistula may continue to drain a substantial amount of blood.

Outcomes of upper arm arteriovenous fistulas for maintenance hemodialysis access.

HYPOTHESIS: Radiocephalic fistulas for maintenance hemodialysis access are not feasible in all patients with end-stage renal disease. Our aim was to review our experience with 3 types of upper arm arteriovenous fistula (AVF) to ascertain whether they are reasonable alternatives to radiocephalic fistulas and which, if any, have superior performance. PATIENTS AND METHODS: Patient medical records were retrospectively reviewed. The main outcomes were maturation rate, time to maturation, assisted maturation rate, complication rates, reintervention rates, primary and assisted primary patency rates, and effects of comorbidities. RESULTS: Eighty-six patients with end-stage renal disease underwent creation of a brachiocephalic, brachiobasilic, or brachial artery-to-median antecubital vein AVF. Overall, 80% matured, with 23% requiring an intervention to achieve maturity. The mean time to maturation was 3.8 months; 47% had a complication (inability to access, thrombosis, and so on), and 43% required additional interventions. The overall primary patency and assisted primary patency rates at 12 months were 50% and 74%, respectively. Brachiobasilic AVFs not superficialized immediately often needed a second operation. There were no significant differences in patency rates among the 3 AVF types. The AVFs in patients with diabetes took 2 months longer to mature than did those in patients without diabetes. CONCLUSIONS: An upper arm AVF is a reasonable alternative for maintenance hemodialysis access when a radiocephalic AVF is not possible. There are 3 valid options from which to choose to best accommodate each patient's antecubital anatomy. Diabetes may adversely affect outcomes. Our data suggest that brachiobasilic AVFs should be superficialized at the initial procedure, if feasible.