SARS CoV2 Omicron Infections Among Vaccinated Maintenance Hemodialysis Patients- outcomes and comparison to Delta variant.

Background Infections with B.1.1.529 (Omicron) variants of SARS-CoV-2 became predominant worldwide since late 2021, replacing the previously dominant B.1.617.2 variant (Delta). While those variants are highly transmissible and can evade vaccine protection, population studies suggested that outcomes from infection with Omicron variants are better compared with Delta. Data regarding prognosis of maintenance hemodialysis (MHD) patients infected with Omicron vs. Delta variants, however, is scarce. Methods This retrospective cohort study includes all patients with end-stage kidney disease treated with MHD in Meir Medical Center, Kfar-Saba, Israel that were diagnosed with SARS-CoV-2 infection between June 2021 and May 2022. Results Twenty-six subjects were diagnosed with the Delta variant and 71 with Omicron. Despite comparable age between groups and higher mean vaccine doses prior to the infection among Omicron group (p<0.001), SARS-CoV-2 infection severity was significantly worse among MHD infected with the Delta variant: 50% developed severe or critical COVID-19 vs. 5% in the Omicron group (p<0.001). Over half of MHD infected with Omicron (57%) were asymptomatic during their illness. 30-day mortality rate for the whole cohort was 5.2%. It was significantly higher among MHD in the Delta group than in the Omicron group (5/26, 19.2% vs. 0/71, p<0.001), as was 90-day mortality rate (5/26, 19.2% vs. 3/71, 4.2%, p=0.02). Conclusions Infection with the SARS-CoV-2 Delta variant was associated with worse outcomes compared with Omicron, among subjects on MHD. However, despite mild disease among vaccinated MHD patients, infection with Omicron variant was still associated with significant 90-day mortality rate.

Intra-Cranial Arterial Calcifications in Hemodialysis Patients.

Background and objectives: Vascular calcification is an integral part of atherosclerosis and has been reported to be an independent risk factor for cardiovascular diSsease. Intra Cranial Arterial Calcifications (ICAC) in maintenance hemodialysis (MHD) is highly prevalent. Materials and Methods: The aim of this retrospective study was to assess the predictors and outcomes of ICAC in MHD patients compared to a control group without kidney disease. A blinded neuroradiologist graded ICAC in brain imaging (computerized tomography) of MHD patients. Age- and sex-matched patients with normal kidney function served as the control group. Results: A total of 280 patients were included in the cohort; 140 of them were MHD patients with a mean ICAC score of 2.3 ± 0.2 versus a mean ICAC score of 1.4 ± 0.2 in the control group (p < 0.01). More than 90% of hemodialysis patients in our study had some degree of ICAC. Lower albumin and higher phosphorus and CRP levels were associated with increased ICACs. The multivariate analysis model for predictors of 1-year mortality demonstrated an increased odds ratio for mortality as the ICAC score increased. Conclusions: ICAC is very prevalent among MHD patients and results not simply from passive deposition of calcium and phosphate but rather from complex and active processes involving inflammation and structural changes in blood vessels. ICAC independently predicted all-cause mortality and may help with risk stratification of this high-risk population.

Acute Kidney Injury and Rehabilitation Outcomes among Elderly Patients with Chronic Kidney Disease.

INTRODUCTION: The incidence of chronic kidney disease (CKD) is growing rapidly, along with the increasing geriatric population. CKD patients have higher incidence of fractures, stroke, and hospitalizations requiring rehabilitation. This is accompanied with the need for suitable rehabilitation programs to decrease disability and improve functionality to help elderly CKD patients maintain independence in activities of daily living. Considering that survivors of acute kidney injury (AKI) tend to experience decreased quality of life with increased frailty, rehabilitation in the elderly with kidney injury becomes even more complex. The aim of this study was to examine the impact of AKI on the outcomes of rehabilitation among elderly patients with CKD. METHODS: For this retrospective, observational study, the electronic medical records of all patients who were hospitalized in the rehabilitation department were reviewed. We assessed functional status at the beginning and end of rehabilitation, renal outcome, and all-cause mortality among elderly patients with CKD who experienced an AKI and compared them to those who did not have an AKI. RESULTS: The study cohort included 183 elderly patients with non-dialysis-dependent CKD. Patients with AKI (23% of study cohort) had a higher prevalence of heart failure and lower baseline estimated glomerular filtration rate, as compared with patients who did not have AKI. They were admitted to rehabilitation at a poorer functional capacity and were also discharged with lower functional independence measure scores. Overall odds ratio for all-cause death among patients with AKI versus without AKI was 3.2 (95% CI: 1.6-6.5; p = 0.001). CONCLUSION: AKI and CKD are interrelated syndromes. AKI was prevalent among elderly CKD patients and was associated with worse rehabilitation outcomes and higher mortality compared to similar patients without AKI.

The Long-Term Outcome of Kidney Transplant Recipients in the Eighth Decade Compared With Recipients in the Seventh Decade of Life.

BACKGROUND: With the aging of the population, more older patients are being considered for kidney transplantation; therefore, it is crucial to evaluate the risks and benefits of transplantation in this population. This study aimed to assess long-term outcomes of kidney transplantation in a cohort of patients who underwent kidney transplantation at age >70 years, compared with patients aged 60 to 69 years at transplantation. METHODS: Included in the study were 261 consecutive kidney transplant recipients: 52 were aged >70 years, and 209 were aged 60 to 69 years at transplantation. Data were collected retrospectively and analyzed using multivariate logistic regression to identify potential outcome risk factors. RESULTS: The number of transplants in both groups increased during the study period. Mortality after transplantation was strongly correlated to age (hazard ratio [HR] = 1.11; 95% CI, 1.05-1.18; P < .001), deceased donor (HR = 2.0; 95% CI, 1.1-3.8; P = .034), and pretransplant diabetes (HR = 2.9; 95% CI, 1.7-4.9; P = .001). Recipients aged >70 years had an increased risk of death censored graft failure (HR = 2.98; 95% CI, 1.56-5.74; P = .001). In living donor transplants, 3-year survival was 80% in recipients age >70 years, compared with 98% in the 60- to 69-year group. Five-year survival was 71% and 92%, respectively. In deceased donor transplants, 3-year survival was 63% and 78%, and 5-year survival was 58% and 72%, respectively. The risk of malignancy (excluding nonmelanotic skin cancer) was nearly triple in the age >70 years group (HR = 2.96; 95% CI, 1.3-6.8; P = .01). CONCLUSIONS: Patient and graft survival in kidney recipients in the eighth decade is worse compared with recipients in the seventh decade of life. However, it is improved with living kidney donation.

Neutrophil reactive oxygen formation, bacterial infections and mortality in malnourished hemodialysis patients: Evaluation of clinical outcomes.

INTRODUCTION: Patients with end stage kidney disease undergoing maintenance hemodialysis (MHD) are prone to malnutrition and infections. OBJECTIVE: The objective of this study was to evaluate the effect of polymorphonuclear (PMN) cell dysfunction on clinical outcomes of MHD patients, in association with nutritional status. METHODS: This prospective study investigated 39 MHD patients by evaluating the oxidative activity of their PMN cells using Phorbol 12-Myristate-13-Acetate (PMA) stimulation. Blood samples were taken from each participant at dialysis initiation. Demographics, laboratory data, and clinical outcomes during a 24-month follow-up period were obtained from electronic medical records. RESULTS: Phagocytic activity was described in percentiles of mean fluorescence intensity (MFI) of PMA levels. There were no differences in comorbidities between patients with low or high MFI-PMA percentiles. Patients in the lowest (25th) MFI-PMA percentile (N = 10) had poorer nutritional status and more frequent severe infections compared to the other 29 patients (4.3 ± 3.4 events versus 2 ± 2.2 events, p = 0.017). Furthermore, they had more frequent hospitalizations (>3) due to infections (70% versus 41%, p = 0.073) and their mortality rate was higher (80% versus 31%, p = 0.007). The odds ratio for all-cause mortality was 8.85. In multivariate analysis, the MFI-PMA percentile and ischemic heart disease were the strongest predictors of all-cause mortality (p = 0.02 and p = 0.005, respectively). CONCLUSIONS: Low MFI-PMA levels were associated with poor nutritional status and adverse clinical outcomes and might serve as a prognostic biomarker, predicting severe infections and mortality among malnourished MHD patients.

Clinical efficacy of the fourth dose of the BNT162b2 vaccine in maintenance dialysis patients.

BACKGROUND AND OBJECTIVES: Highly effective vaccines against severe acute respiratory syndrome virus 2 have been developed and administered worldwide. However, protection from coronavirus disease 2019 is not absolute and an optimal vaccination regimen needs to be established. This study assessed the clinical efficacy of the coronavirus disease 2019 vaccine among dialysis patients receiving 3 or 4 doses of vaccine. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This retrospective study was conducted using the electronic database of Clalit Health Maintenance Organization in Israel. Chronic dialysis patients treated with either hemodialysis or peritoneal dialysis during the coronavirus disease 2019 pandemic were included. We compared clinical outcomes of patients who had received three or four doses of the severe acute respiratory syndrome virus 2 vaccine. RESULTS: This study included 1,030 patients on chronic dialysis, with a mean age of 68 ± 13 years. Among them, 502 patients had received 3 doses of the vaccine and 528 received 4 doses. Severe acute respiratory syndrome virus 2 infection rates, severe COVID-19 that resulted in hospitalizations, COVID-19-related mortality and all-cause mortality rates were lower among chronic dialysis patients who received a fourth dose of vaccine as compared to those who received only 3 doses (after controlling for age, sex and comorbidities). Despite lower mortality rates observed with the Omicron variant, the fourth dose was significantly associated with reduced COVID-19-related mortality (1.7% vs. 3.8%, p = 0.04). Odds ratio for COVID-19-related mortality was 0.44 with 95% CI 0.2-0.98. CONCLUSIONS: As seen in the general population and with previous vaccine boosters, the fourth dose of the BNT162b2 vaccine reduced rates of severe COVID-19-related hospitalization and mortality among chronic dialysis patients. Further studies are needed to establish the optimal regimens of vaccination for patients on chronic dialysis.

Dialysis modality, humoral response to vaccine, and SARS-CoV-2 infection risk: Comparative prospective evaluation.

BACKGROUND: COVID-19 vaccinations have a central role in decreasing severe SARS-CoV-2 disease complications. This study investigated the long-term humoral immune response to BNT162b2 vaccine among hemodialysis (HD) versus peritoneal dialysis (PD) patients, and their relative risk for COVID-19 infection. METHODS: This prospective, observational study included maintenance HD and PD patients who had received at least two BNT162b2 vaccine doses. Levels of antibodies targeting SARS-CoV-2 spike protein were measured 6 and 12 months after the first vaccine dose, and 2-3 weeks after the third and fourth vaccine doses. Patients were divided according to dialysis modality (HD or PD). Humoral response was evaluated at different time points among different vaccine regimens (two vs. three vs. four doses of vaccine). An adjusted multivariate model was used to assess cumulative risk for SARS-CoV-2 infection. RESULTS: Eighty-seven HD and 36 PD patients were included. Among them, 106 (86%) received at least three vaccine doses. Both HD and PD patients demonstrated marked increases in humoral response 2-3 weeks after the third dose (mean anti-S antibody increased from 452 ± 501 AU/mL to 19,556 ± 14,949 AU/mL, p < 0.001). By 6 months after the third dose, antibody titers had declined significantly (mean anti-S antibody 9841 ± 10,493 AU/mL, p < 0.001). HD patients had higher risk for SARS-CoV-2 infection than PD patients (OR 4.4 [95% CI 1.4-13.6], p = 0.006). In multivariate analysis, the most important predictor for SARS-CoV-2 infection was dialysis modality. CONCLUSION: This study found a high antibody response rate after the third and fourth doses of BNT162b2 vaccine among dialysis patients. Hemodialysis as dialysis modality is an important predictor of COVID-19 infection, despite similar humoral responses to vaccine in peritoneal dialysis.

Humoral Response to Hepatitis B and COVID-19 Vaccine among Maintenance Hemodialysis Patients.

Maintenance hemodialysis (MHD) patients have impaired immunological responses to pathogens and vaccines. In this study, we compared the humoral response to HBV and COVID-19 vaccines in a cohort of MHD patients. Demographic and clinical characteristics of vaccine responders and non-responders were also compared, and the association between the humoral responses to both vaccines was evaluated. The cohort included 94 MHD patients who were vaccinated at least once for HBV and twice for COVID-19. Among the 94 patients, 28 (29.8%) did not develop protective titers to HBV. Hypertension, coronary heart disease, and heart failure were more common in non-responders. Among MHD patients, 85% had positive IgG anti-spike SARS-CoV-2 levels 6 months after two doses of BNT162b2 (Pfizer/Biotech) vaccine. Age and immunosuppressive therapy were the main predictors of humoral response to COVID-19 vaccine. We did not find any association between non-responders to HBV and non-responders to COVID-19 vaccine. There was no difference in IgG anti-spike titers between HBV responders and non-responders (505 ± 644 vs. 504 ± 781, p = 0.9) Our results suggest that reduced humoral response to hepatitis B is not associated with reduced response to COVID-19 vaccine. Different risk-factors were associated with poor immune response to HBV and to COVID-19 vaccines.

Clinical Outcomes of Vascular Accesses in Hemodialysis Patients.

BACKGROUND: Reliable vascular access is a fundamental tool for providing effective hemodialysis. Vascular access dysfunction is associated with increased morbidity and mortality among hemodialysis patients. Current vascular access guidelines strongly recommend creating an arteriovenous fistula (AVF) as the first option; however, a substantial proportion of new AVFs may not be usable. OBJECTIVES: To assess possible predictors of primary and secondary failure of vascular access. METHODS: This retrospective cohort study included all vascular access sites created at Meir Medical Center from 2006 through 2012. Vascular access site, primary and secondary failure rates, and relevant demographic and clinical data were recorded during 60 months of follow-up. RESULTS: A total of 612 vascular accesses were created and followed for a median of 32 ± 29.4 months. Of these, 490 (80%) were suitable for initiating hemodialysis. Vascular access site was the most important predictor of primary failure but did not predict secondary failure. Co-morbidities such as diabetes mellitus and congestive heart failure, as well as the use of antiplatelet agents did not predict primary or secondary failure. Preoperative vascular mapping using Doppler ultrasonography was performed in 36.4% of cases and was not associated with lower rates of primary or secondary failure. CONCLUSIONS: Vascular access site is an important predictor of primary failure. We did not find a benefit of pre-operative vessel mapping or chronic antiplatelet therapy in terms of decreasing primary and secondary failure rates. Physicians should carefully consider the characteristics of the patient and blood vessels before creating vascular access in patients requiring chronic hemodialysis.

Humoral Response and SARS-CoV-2 Infection Risk following the Third and Fourth Doses of the BNT162b2 Vaccine in Dialysis Patients.

The optimal SARS-CoV-2 vaccination schedule in dialysis patients and the potential need for a fourth vaccine dose are debatable. We prospectively assessed the humoral responses to three and four doses of BNT162b2 among dialysis patients. The study included 106 dialysis patients; 60 (56.6%) and 46 (43.4%) received 3 and 4 vaccine doses, respectively. Anti-spike (anti-S) antibody titers significantly increased after the third vaccine dose, followed by a decline, yet still remained higher than all previous measurements. The fourth vaccine dose led to another profound rise in anti-S titers. The absolute increase following the fourth dose correlated with response to the third dose. Infection risk however was similar between patients vaccinated with three or four doses.

The efficacy of rehabilitation for elderly chronic kidney disease patients: a retrospective, single-center study.

BACKGROUND: As the geriatric population is growing rapidly, so is the prevalence of chronic kidney disease (CKD). Suitable rehabilitation programs are needed to decrease disability and improve functionality to maintain independence in activities of daily life. AIMS: To assess the impact of CKD on the efficacy of rehabilitation in the geriatric population. METHODS: Retrospective single-center cohort study, demographic and clinical data of 190 elderly, non-dialysis dependent CKD patients, who underwent rehabilitation, during 2016-2020 were analyzed. RESULTS: Early CKD patients had longer duration of rehabilitation as compared with advanced CKD (32.6 ± 19.5 vs. 25.1 ± 17.6 days, p = 0.011) and tended to be more independent at discharge (37.2% vs. 27.9%, respectively; p < 0.001). Duration of rehabilitation, Mini-Mental State Examination (MMSE), Functional Independence Measurement (FIM) admission and estimated GFR were important predictors of FIM at discharge. Age was negatively correlated with admission FIM, eGFR, MMSE, and discharge FIM. The odds ratio for mortality among patients with advanced as compared to early CKD was 2.197 (CI 95% 1.159-4.166, p = 0.015). DISCUSSION: Existing rehabilitation programs raise questions of suitability for the consistently aging population, play an indispensable part in the goal of achieving functional independence in the elderly and should promote further investigation of the efficacy of rehabilitation for CKD patients. CONCLUSIONS: Advanced CKD was associated with lower FIM at admission and discharge, shorter duration of rehabilitation and more dependence at discharge, as compared to patients with early CKD. Implementing a multidisciplinary team, focused on the specific needs of geriatric CKD patients, with clear, objective parameters and goals may lead to better rehabilitative outcomes, with decreased public and private costs of ongoing care.

Humoral response and breakthrough infections with SARS-CoV-2 B.1.617.2 variant in vaccinated maintenance hemodialysis patients.

INTRODUCTION: Breakthrough COVID-19 may occur in vaccinated people, and may result from declining vaccine effectiveness or highly transmittable SARS-CoV-2 variants, such as the B.167.2 (delta) variant. We investigated risk factors and outcomes for infection with the delta variant among vaccinated hemodialysis patients. METHODS: Patients on maintenance hemodialysis who received two doses of the BNT162b2 (Pfizer-BioNTech) vaccine were analysed according to having developed COVID-19 (study group) or not (control group), in a retrospective, observational, comparative study. We compared risk-factors for developing breakthrough COVID-19 and assessed clinical outcomes, including 30-day mortality rates. RESULTS: Twenty-four cases of breakthrough SARS-CoV-2 infection were compared to 91 controls without infection. Breakthrough infection was associated with chronic immunosuppressive treatment, hematological malignancies, and low antibody levels against SARS-CoV-2 spike protein. All COVID-19 cases occurred at least 5 months after vaccination, and most were caused by the B.1.617.2 variant (at least 23/24 cases). COVID-19 was categorized as severe or critical disease in 11/24 patients (46%), and 54% required hospitalization and COVID-19-directed treatment. The source of infection was nosocomial in 6/24 cases (25%), and healthcare-related in 3/24 (12.5%). Mortality rate was 21%. Overall mortality was significantly higher in patients who developed COVID-19 than in controls (odds ratio for all-cause mortality 7.6, 95% CI 1.4-41, p = 0.002). CONCLUSIONS: Breakthrough COVID-19 with the B.1.617.2 variant can occur in vaccinated hemodialysis patients and is associated with immunosuppression and weaker humoral response to vaccination. Infections may be nosocomial and result in significant morbidity and mortality.

Humoral Response to Pfizer BNT162b2 Vaccine Booster in Maintenance Hemodialysis Patients.

INTRODUCTION: Coronavirus disease is associated with increased morbidity and mortality in maintenance hemodialysis (MHD) patients. Recent breakthrough infection in vaccinated people has led some authorities to recommend a booster dose for patients fully vaccinated 5-8 months ago. We aimed to assess the humoral response of MHD patients following a booster dose with the BNT162b2 vaccine. METHODS: The study included 102 MHD patients vaccinated with 2 doses of the BNT162b2 (Pfizer-BioNTech) vaccine. A third dose (booster) was recommended to all MHD patients in our center and was given to those who opted to receive it, resulting in a booster group and a control group that did not receive the booster. Previous exposure was excluded by testing for the presence of the anti-nucleocapsid antibody (SARS-CoV-2) or positive PCR. We assessed the humoral response before and after the booster dose. RESULTS: Of 66 patients in the booster group, 65 patients (98.5%) developed a positive antibody response, from 472.7 ± 749.5 to 16,336.8 ± 15,397.3, as compared to a sustained decrease in the control group (695.7 ± 642.7 to 383.6 ± 298.6), p < 0.0001. No significant adverse effects were reported. Prior antibody titers were positively correlated to IgG levels following the booster dose. There was a significant association between malnutrition-inflammation markers and the humoral response. CONCLUSIONS: Almost all MHD patients developed a substantial humoral response following the booster dose, which was significantly higher than levels reported for MHD patients following administration of 2 doses alone. Further studies and observations are needed to determine the exact timing and dosing schedule.

Diastolic blood pressure is associated with brain atrophy in hemodialysis patients: A single center case-control study.

Brain atrophy (BA) is often found in neuroimaging of hemodialysis patients, representing parenchymal cerebral damage. Likely contributing factors to BA are age, chronic hypertension, diabetes mellitus and other cardiovascular risk factors of atherosclerosis that are also common among hemodialysis patients. BA may also occur due to focal ischemia and hypoperfusion during hemodialysis. However, data on optimal blood pressure (BP) in these patients are limited. The goal of this study was to determine whether the prevalence and severity of BA would be higher among hemodialysis patients with lower BP. A blinded neuroradiologist graded BA of all hemodialysis patients who underwent brain non-contrast computerized tomography (CT) from 2015 to 2017 in our institution. Age- and sex-matched patients with normal kidney function who underwent brain CT during the same period and technique served as the control group. A total of 280 patients were included in this retrospective study, with average BP of 140/70 mmHg among hemodialysis patients and 142/75 mmHg in the control group. BA was more common in dialysis patients and its severity increased with age and traditional cardiovascular risk factors. We observed a significant negative correlation between diastolic BP (DBP) at dialysis initiation and BA. Average DBP decreased with increasing severity of BA. These findings were observed in both hemodialysis and non-CKD patients. BA was associated with lower DBP, which may induce cerebral hypoperfusion and ischemia. This finding should discourage over-treatment of hypertension among hemodialysis patients.

The efficacy of rehabilitation for elderly hemodialysis patients: a retrospective, single center study.

INTRODUCTION: Chronic kidney disease is associated with an increased risk of vascular events and bone fractures, and its prevalence is increasing. Despite the high frequency of strokes and bone fractures in the hemodialysis (HD) population, the few studies on rehabilitation outcomes in this population are controversial. The current study assessed the efficacy of inpatient rehabilitation for hemodialysis patients. METHODS: This is a retrospective, observational review of medical records of all chronic HD patients who underwent rehabilitation in Meir Medical Center, from 2008 to 2018. The primary endpoint was functional independence measure (FIM) score at discharge. Secondary endpoints were all-cause mortality, efficiency of rehabilitation and discharge destination from rehabilitation. RESULTS: During the study period, 162 patients were included in the analysis. 76/81 (93.8%) hemodialysis patients had improvement FIM scores. There were no significant differences in FIM scores at discharge between hemodialysis patients and controls. However, the efficiency of rehabilitation expressed by FIM efficiency (progress measured as FIM gain/length of stay in rehabilitation) was higher in hemodialysis vs. controls. 73% of hemodialysis patients were discharged home. There was no significant difference in discharge destinations between groups. Both 30-day and 1-year mortality after admission to rehabilitation was higher in HD vs. controls (OR 4.97, 95% CI 1.4-18.2, p = 0.008 and OR 4.98, 95% CI 1.8-14.1, p value = 0.001, respectively). CONCLUSION: Hemodialysis patients may benefit from inpatient rehabilitation. Although mortality was higher, efficacy of rehabilitation for hemodialysis patients is comparable to non-dialysis patients and is no less effective.