Effect of COVID-19 on Kidney Graft Function One Year after Onset.

Background and Objectives: Kidney transplant recipients (KTRs) are at a higher risk of severe COVID-19 development. The course of the infection may vary. Long-term consequences for graft function are still being studied. We investigate whether the clinical course of SARS-CoV-2 infection among KTRs had a long-term effect on graft function. Patients and method: 128 KTRs with confirmed SARS-CoV-2 infection were included in the study. They were divided into two groups: mild (without the need for oxygen therapy; n = 91) and severe (with the need for oxygen therapy; n = 21). Baseline characteristics and medical data, especially creatinine level, estimated glomerular filtration rate (eGFR) CKD-EPI, and proteinuria, were analyzed. The main outcomes were the absolute and relative change in eGFR during the one-year follow-up after COVID-19. In the final models, sex, age, smoking, presence of diabetes mellitus (DM), and cardiovascular disease (CVD) were included. Results: KTRs with severe COVID-19 were older, more likely to smoke, and had DM and CVD more frequently. Our analysis reveals that COVID-19 severity was associated with a significantly more pronounced relative eGFR decline one year after recovery only in males [-13.94 (95% CI: -25.13 to -2.76, p = 0.015) percentage points]. One year after the disease onset, males with a severe course of the infection had a higher eGFR decline than those with a mild one. The COVID-19 severity did not affect eGFR loss in females. Conclusions: In KTRs suffering from COVID-19, deterioration of graft function was noticed. The eGFR decline was associated with disease severity and sex. It indicates a need for further research, observation, and preventive actions for KTRs, especially males.

Hemodialyzed Individuals' Left Spatial Attentional Bias Is Normalized Following Successful Kidney Transplantation.

BACKGROUND: Healthy people have a leftward spatial attentional bias, called pseudoneglect. Individuals with end-stage renal disease (ESRD) who are receiving hemodialysis often demonstrate an increase in their leftward spatial attentional bias. Whereas a successful kidney transplant often improves the cognitive functions of individuals who previously received hemodialysis, the effect of a kidney transplant on this abnormal allocation of spatial attention has not been investigated. OBJECTIVE: To investigate the effects of kidney transplant on individuals who were being treated with dialysis and had an increase in their left spatial attentional bias. METHOD: The performance of 20 hemodialyzed individuals with ESRD on the line bisection test was compared to that of 17 demographically matched individuals with ESRD, who had received a kidney transplant, and 23 demographically matched healthy controls (HC). RESULTS: All of the participants exhibited a left spatial bias on the line bisection task. When compared with the HC, the hemodialyzed individuals demonstrated a significantly greater left spatial bias. There was, however, no difference in spatial bias between the HC and the individuals who had received a kidney transplant. CONCLUSION: A successful kidney transplant can improve patients' abnormal leftward allocation of spatial attention. However, future studies are needed to better understand the mechanisms of this spatial attentional bias in hemodialyzed individuals and the normalization of bias following transplantation.

Safety and Tolerability of the BNT162b2 mRNA COVID-19 Vaccine in Dialyzed Patients. COViNEPH Project.

Background and Objectives: The Pfizer-BioNTech (BNT162b2) COVID-19 mRNA vaccine has demonstrated excellent efficacy and safety in phase 3 trials. However, no dialyzed patients were included, and therefore safety data for this patient group is lacking. The aim of the study was to assess the safety and tolerances of vaccinations with BNT162b2 performed in chronically dialyzed patients. Materials and Methods: We performed a prospective cohort study including a group of 190 dialyzed patients (65% male) at median age 68.0 (55-74) years. 169 (89.0%) patients were treated with hemodialysis and 21 (11.0%) with peritoneal dialysis. The control group consisted of 160 people (61% male) without chronic kidney disease at median age 63 (range 53-77) years. Both groups were vaccinated with BNT162b2 with a 21-day interval between the first and the second dose. Solicited local and systemic reactogenicity, unsolicited adverse events and antipyretic and pain medication use were assessed with a standardized questionnaire. The toxicity grading scales were derived from the FDA Center for Biologics Evaluation and Research guidelines. Results: 59.8% (dose 1), 61.4% (dose 2) and 15.9% (dose 1), 29.4% (dose 2) dialyzed patients reported at least one local and one systemic reaction respectively within seven days after the vaccination. Many local and systemic solicited reactions were observed less frequently in dialyzed patients than in the age and sex matched control group and much less frequently than reported in the pivotal study. They were mostly mild to moderate, short-lived, and more frequently reported in younger individuals and women. No related unsolicited adverse events were observed. Conclusions: We have shown here that BNT162b2, an mRNA vaccine from Pfizer-BioNTech against SARS-COV-2 is safe and well-tolerated by dialyzed patients. The results can be useful for the nephrological community to resolve patients' doubts and reduce their vaccine hesitancy.

Leftward Bias of Visual Attention in Patients with End-Stage Renal Disease Receiving Dialysis: A Neglected Phenomenon.

BACKGROUND AND OBJECTIVE: Patients with end-stage renal disease (ESRD) who are receiving dialysis often have cognitive and behavioral changes, including impairments in sustained attention. Impairments in sustained attention appear to be the consequence of right hemisphere dysfunction. Right hemisphere brain networks are also important for the allocation of spatial attention. Therefore, the objective of this study was to learn whether patients with ESRD receiving dialysis might also have a spatial attentional bias. PARTICIPANTS AND METHODS: Eighteen nondemented patients with ESRD receiving dialysis but without any neurologic diseases (age range: 20 to 60 years) and 18 demographically matched healthy controls participated in this study. Participants performed a standard line bisection task using 24 horizontal lines (24 cm long and 2 mm thick) that were sequentially placed at eye level on a white board. RESULTS: Patients receiving dialysis had a significantly greater leftward bias than healthy controls. CONCLUSIONS: Patients with ESRD receiving dialysis appear to have an impaired ability to correctly allocate their spatial attention (spatial neglect). Although the reason for the patients' leftward bias needs to be elucidated, ESRD and/or dialysis may have induced right frontal-subcortical dysfunction that disinhibited the right parietal lobe, producing a left-sided attentional bias. Further studies are needed to test this hypothesis.

Disorders of the anterior attentional-intentional system in patients with end stage renal disease: Evidence from reaction time studies.

OBJECTIVE: Dialyzed patients with end-stage renal disease (ESRD) have been reported to have several neurobehavioral impairments that are often accompanied by structural and functional abnormalities of frontal-subcortical networks. Whereas the anterior attentional-intentional systems responsible for the allocation of attention and preparation for action (intention) are mediated by these frontal-subcortical networks, these functions have not been specifically investigated in this population. METHOD: Twenty-three non-demented dialyzed patients with ESRD were compared with 25 matched controls on the performance on four reaction time (RT) subtests from the ROtman-Baycrest Battery to Investigate Attention (ROBBIA). These included measures of Simple, Choice, and Prepare RTs as well as a Concentrate task. RESULTS: In the Prepare RT task with a warning signal presented 1s before the onset of imperative stimulus, the patients' performance was not different than the controls; however, dialyzed patients became significantly slower than controls in the Prepare 3s warning condition as well as on all other RT measures. Nonetheless, both groups exhibited a gradual decrease in RT with increasing interstimulus intervals, with no group difference in the number and type of errors. CONCLUSIONS: These results suggests, that while with external preparatory stimuli, the dialyzed ESRD patients may be able to acutely increase their arousal and enhance their allocation of selective attention or action-preparation, they appear not to be able to maintain this enhanced preparatory status. Whereas these results help to elucidate a potential source of disability in this patient population, future studies will need to examine if this deficit is primarily attentional, intentional or both (arousal), as well as explore possible treatments.

The Efficacy and Safety of High-Dose Cholecalciferol Therapy in Hemodialysis Patients.

Vitamin D deficiency and insufficiency are highly prevalent in CKD, affecting over 80% of hemodialysis (HD) patients and requiring therapeutic intervention. Nephrological societies suggest the administration of cholecalciferol according to the guidelines for the general population. The aim of the observational study was to evaluate the efficacy and safety of the therapy with a high dose of cholecalciferol in HD patients with 25(OH)D deficiency and insufficiency to reach the target serum 25(OH)D level > 30 ng/mL. A total of 22 patients (16 M), with an average age of 72.5 ± 13.03 years and 25(OH)D concentration of 13.05 (9.00-17.90) ng/mL, were administered cholecalciferol at a therapeutic dose of 70,000 IU/week (20,000 IU + 20,000 IU + 30,000 IU, immediately after each dialysis session). All patients achieved the target value > 30 ng/mL, with a mean time of 2.86 ± 1.87 weeks. In the first week, the target level of 25(OH)D (100%) was reached by 2 patients (9.09%), in the second week by 15 patients (68.18%), in the fourth week by 18 patients (81.18%), and in the ninth week by all 22 patients (100%). A significant increase in 1,25(OH)2D levels was observed during the study. However, only 2 patients (9.09%) achieved a concentration of 1,25(OH)2D above 25 ng/mL-the lower limit of the reference range. The intact PTH concentrations remained unchanged during the observation period. No episodes of hypercalcemia were detected, and one new episode of hyperphosphatemia was observed. In conclusion, our study showed that the administration of a high-therapeutic dose of cholecalciferol allowed for a quick, effective, and safe leveling of 25(OH)D concentration in HD patients.

Intradialytic Tolerance and Recovery Time in Different High-Efficiency Hemodialysis Modalities.

There are several forms of maintenance high-efficiency hemodialysis (HD), including hemodiafiltrations (HDF) in different technical modes and expanded HD, using dialyzers with medium cut-off membranes. The aim of the study was to assess the intradialytic tolerance and length of dialysis recovery time (DRT) in these modalities. This is an exploratory, crossover study in maintenance HD patients with low comorbidity and no clinical indications for the use of high-efficiency HD, who were exposed to five intermittent dialyses in random order: high-flux hemodialysis (S-HD), expanded HD (HDx), pre-dilution HDF (PRE-HDF), mix-dilution HDF (MIX-HDF) and post-dilution HDF (POST-HDF). Twenty-four dialysis sessions of each method were included in the analysis. Dialysis parameters, including blood flow rate, dialysis fluid flow rate and temperature, and pharmacological treatment were constant. Average total convection volume for post-HDF, pre-HDF and mix-HDF were 25.6 (3.8), 61.5 (7.2) and 47.1 (11.4) L, respectively. During all therapies, patients were monitored for the similarity of their hydration statuses using bioimpedance spectroscopy, and for similar variability over time in systemic blood pressure and cardiac output, while peripheral resistance was monitored using impedance cardiography. The lowest frequency of all intradialytic adverse events were observed during HDx. Delayed DRT was the shortest during PRE-HDF. Patients were also more likely to report immediate recovery while receiving PRE-HDF. These differences did not reach statistical significance; however, the study results suggest that intradialytic tolerance and DRT may depend on the dialysis method used. This supports the need of taking into account patient preferences and quality of life while individualizing high-efficiency therapy in HD patients.

Comprehensive Assessment of Eyes in Kidney Transplant Recipients after Recovering from COVID-19.

INTRODUCTION: Patients after organ transplantation with COVID-19 have a higher risk of morbidity and mortality than patients in the general population. There are single studies that assess the eyes of COVID-19 patients, but there are no such studies on organ transplant recipients. The purpose of this study was to comprehensively examine the eyes of kidney transplant recipients (KTR) after recovery from mild to moderate SARS-CoV-2 infection. METHODS: A total of 40 KTR after COVID-19 and 20 KTR without clinical and immunological symptoms of SARS-CoV-2 infection as a control group was qualified for the cross-sectional study. A total of 76 eyes from 38 KTR on an average of 7 weeks after COVID-19 and 36 eyes from 18 KTR from the control group were studied. The participants underwent an ophthalmological examination, and the retinal and choroid vessels and nerves were assessed by optical coherence tomography angiography. RESULTS: We found a lower vessel density (VD) in the deep capillary plexus in the central part of the retina (VD deep central) of the study group. Women had significantly lower VD deep central in the study group (15.51 vs. 18.91, p < 0.001). Multivariate linear regression analysis confirmed an independent, negative impact of COVID-19 (p < 0.001) and female gender (p = 0.001) on VD deep central. CONCLUSION: The results of our study confirmed that changes in microcirculation induced by SARS-CoV-2 infection may affect the retinal vessels in KTR. Mild to moderate COVID-19 in KTR resulted in a significant reduction in VD deep central of the retina, with these changes being more common in females.

Risk factors for selective cognitive decline in dialyzed patients with end-stage renal disease: evidence from verbal fluency analysis.

Although dialyzed patients often have cognitive problems, little is known about the nature of these deficits. We hypothesized that, in contrast to semantic fluency relying mainly on temporal lobes, phonemic fluency, preferentially depending on functions of frontal-subcortical systems, would be particularly sensitive to the constellation of physiological pathological processes associated with end-stage renal disease and dialysis. Therefore, we longitudinally compared phonemic and semantic fluency performance between 49 dialyzed patients and 30 controls. Overall, patients performed below controls only on the phonemic fluency task. Furthermore, their performance on this task declined over time, whereas there was no change in semantic fluency. Moreover, this decline was related to the presence of hypertension and higher blood urea nitrogen. We suggest that these findings may be due to a combination of vascular and topic effects that impact more on fronto-subcortical than temporal lobe networks, but this speculation requires direct confirmation.

COVID­19 in patients requiring renal replacement therapy: an overview of current data and future challenges.

Patients with chronic kidney disease, especially those on renal replacement therapy, demonstrate increased incidence and mortality from COVID­ 19, as compared with the general population. One of the main reasons for this phenomenon is a dysfunction of the immune system associated with its accelerated aging, weakened immune functions, impaired regulation of proinflammatory reactions, chronic inflammation, and immunosuppressive therapy. Most of these patients have a high rate of comorbidities, which may also have a negative impact on the severity of COVID­ 19 and prognosis. Introduction of COVID 19 vaccines has significantly changed the course of the fight against the pandemic. Due to the very severe disease, in many countries the patients receiving renal replacement therapy were prioritized for vaccination right after health care professionals. Differences in the response to vaccination were noted, which required an individualized approach and modification of the vaccination program in this patient group. Difficulties in assessing these issues are due to the differences in the research methodology used in the available studies and their observational nature. Moreover, response to vaccination varied over time depending on the geographic region and variant of the virus causing the infection. The epidemiology was significantly influenced by the improved prevention methods and treatment of infections as well as the growing percentage of vaccinated and convalescent people. We present the most important differences in the epidemiology of COVID­ 19, the course of the disease, prognosis, and prevention, as well as the challenges associated with improving the prognosis in patients receiving renal replacement therapy.

Analysis of Experiences in Preventing COVID-19 in Hemodialysis Centers of the North of Poland before the Era of Vaccination.

BACKGROUND: The appearance of very contagious SARS-CoV-2 variants and waning vaccine immunity may indicate the need to return to using universal methods of preventing the spread of COVID-19. METHODS: We performed a multicenter retrospective cohort survey study to describe the methods used in dialysis units to prevent and control the spread of SARS-CoV-2 and also the association between these methods and the incidence of COVID-19 among hemodialyzed (HD) patients before the era of vaccination. The study population included all maintenance HD patients (n = 1569) in 14 dialysis units in the Pomeranian Voivodeship. RESULTS: The group of 352 patients (199 men, 153 female) were confirmed for COVID-19. The absolute cumulative incidence in the studied period was 22.4%. It varied widely by dialysis units, ranging from 9.4% to 36.9%. Universal preventive methods were applied by all units. Different additional methods were implemented in some stations with varying frequency (36-86%). In order to quantify the scale of the applied additional preventive methods, we calculated a summary prevention index (PI), i.e., one point for one additional method. Lower incidence was found in centers applying dialysis in isolation of patients hospitalized due to diseases requiring hospitalization (17.42% ± 6.89 vs. 26.54 ± 6.34; p = 0.028) and higher incidence in medium-size dialysis centers (ANOVA F: p = 0.017). Significant inverse correlation between PI and incidence was demonstrated as well (r = -0.759; p = 0.002). CONCLUSIONS: The higher the number of implemented preventive measures, the lower the risk of COVID-19 infection in HD patients. Among applied procedures the isolation of hospitalized patients is of significant importance. The measures proved to be effective in prevention before the vaccination era should be continued, as the threat of SARS-CoV-2 still exists.

Heterologous high dose SARS-CoV-2 mRNA vaccine booster may improve immune response in seronegative kidney transplant recipients.

Introduction: Three-dose mRNA vaccination against COVID-19 is unable to elicit a sufficient immune response in immunocompromised subjects. Methods: The aim of the study was to conduct a retrospective evaluation of the efficacy of a heterologous mRNA booster with mRNA-1273 in constantly seronegative kidney transplant recipients (KTRs) after three doses of the BNT162b2 mRNA vaccine. Twelve seronegative KTRs received a mRNA-1273 booster 5 months after the third dose of BNT162b2. Results: A total of 5 out of 12 patients (41.7%) seroconverted, with a mean titer of 353 BAU/ml. Conclusions: The administration of a heterologous mRNA vaccine as a booster may be an effective alternative for achieving post-vaccination immunity in seronegative KTRs.

Predictors of Mortality in Hemodialyzed Patients after SARS-CoV-2 Infection.

INTRODUCTION: The determinants of COVID-19 mortality are well-characterized in the general population. Less numerous and inconsistent data are among the maintenance hemodialysis (HD) patients, who are the population most at risk of an unfavorable prognosis. METHODS: In this retrospective cohort study we included all adult HD patients from the Pomeranian Voivodeship, Poland, with laboratory-confirmed SARS-CoV-2 infection hospitalized between 6 October 2020 and 28 February 2021, both those who survived, and also those who died. Demographic, clinical, treatment, and laboratory data on admission, were extracted from the electronic medical records of the dedicated hospital and patients' dialysis unit, and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with 3-month all-cause mortality. RESULTS: The 133 patients (53.38% males) aged 73.0 (67-79) years, with a median duration of hemodialysis of 42.0 (17-86) months, were included in this study. At diagnosis, the majority were considered to have a mild course (34 of 133 patients were asymptomatic, another 63 subjects presented mild symptoms), while 36 (27.07%) patients had low blood oxygen saturation and required oxygen supplementation. Three-month mortality was 39.08% including an in-hospital case fatality rate of 33.08%. Multivariable logistic regression showed that the frailty clinical index of 4 or greater (OR 8.36, 95%CI 1.81-38.6; p < 0.01), D-Dimer of 1500 ng/mL or greater (6.00, 1.94-18.53; p < 0.01), and CRP of >118 mg/L at admission (3.77 1.09-13.01; p = 0.04) were found to be predictive of mortality. CONCLUSION: Very high 3-month all-cause mortality in hospitalized HD patients was determined mainly by frailty. High CRP and D-dimer levels upon admission further confer mortality risk.

Safety and Tolerability of mRNA COVID-19 Vaccines in Kidney Transplant Recipients.

BACKGROUND: COVID-19 mRNA vaccines have demonstrated excellent short-term safety in phase 3 trials. However, no kidney transplant recipients (KTR) were included. The aim of the study was to assess the safety and tolerability of COVID-19 mRNA vaccines in KTR. MATERIALS AND METHODS: A longitudinal controlled study was conducted in 300 KTR and 143 control patients (CRL) without chronic kidney disease who had received 2-dose vaccinations with the mRNA vaccine. Solicited local and systemic reactogenicity and unsolicited adverse events were assessed with a standardized questionnaire. The toxicity grading scales were derived from the FDA guidelines. RESULTS: KTR (62.7% men) with a median (interquartile range) age of 53 (41-63) and transplant vintage of 7.25 (3-13) years did not differ with respect to age and sex distribution from CRL. One hundred percent CRL and 83.3% KTR were vaccinated with BNT162b2 (BionTech/Pfizer); 16.7% KTR received mRNA-1273 (Moderna) vaccine. Any local reactions were present in 84.7% (first dose) and 65.3% (second dose) KTR vs 67.1% and 60.1% CRL within 7 days after the vaccination. Any systemic reactions were reported by 26.7% (first dose) and 20.9% (second dose) KTR vs 24.7 and 35.7% CRL. The most common systemic reactions in KTR were fatigue, headache and myalgia. No serious adverse events were observed. Many systemic reactions were observed less frequently in KTR than CRL. Younger KTR (<54 years) reported any local and any systemic reactions significantly more frequently than older patients. CONCLUSION: mRNA COVID-19 vaccines are safe and well-tolerated by KTR. The results may resolve patients' doubts and reduce their vaccine hesitancy.

COVID-19 vaccination reduces mortality in patients on maintenance hemodialysis.

Patients with chronic kidney disease on maintenance hemodialysis (HD) have a very high risk of death in the course of COVID-19. The aim of the study was to assess the effectiveness of COVID-19 vaccination to reduce the incidence of COVID-19 and the fatality rate in HD patients. A retrospective registry-based cohort study was performed in all HD adult patients in the Pomeranian Voivodeship. Vaccinations were carried out from January to April 2021 with mRNA vaccines, either BNT162b2 or mRNA-1273 with two-dose schedule. In the first analysis (2nd pandemic wave), 1,160 unvaccinated patients were included (59.7% males, 25.7% diabetic). In the second analysis (4th pandemic wave), 1,131 (59.4% male, 30.7% diabetic) individuals were included, 1,042 (92.13%) were fully vaccinated. Three hundred and fifteen HD patients (27.2%) were COVID-19 positive during the 2nd wave, and 6.9% (78/1,131) during the 4th wave. Within the fully vaccinated patients of the 4th wave, 60 were COVID-19 positive, 5.8 vs. 20.2% of unvaccinated COVID-19 positive patients in 2nd wave, respectively. COVID-19 incidence rate ratio (IRR) was 0.21 (4th wave-vaccinated vs. 2nd wave-unvaccinated) indicating a 79% reduction. The IRR between vaccinated and unvaccinated patients of the 4th wave was 0.28 in favor of vaccinated patients with 72% reduction. In the 2nd wave, 93 patients died as a result of COVID-19 (fatality rate: 29.5%). The fatality rate of fully vaccinated patients during the 4th wave was 6.7% (p = 0.004), while the fatality rate in the 4th wave within unvaccinated patients accounted for 11.1%. Significant clinical effectiveness of COVID-19 vaccination was demonstrated in a multicenter study in HD patients.

Changes in Kidney Graft Function in COVID-19 Convalescents.

BACKGROUND: Kidney transplant recipients (KTRs) are at an increased risk of infection with severe acute respiratory syndrome coronavirus 2, with mortality from 13% to over 30%. However, data concerning the influence of COVID-19 on long-term graft function in convalescents is lacking. The aim of this study was to evaluate the influence of COVID-19 on graft function at 6 months after recovery. METHODS: A longitudinal controlled study was conducted in a group of 1058 KTRs. Of 180 patients with COVID-19 in the past, 77 KTRs (45 male) with a mean age 50.57 ± 13.37 years, Charlson Comorbidity Index of 3 (median; interquartile range [IQR], 3-5), Fragility Score of 3 (median; IQR, 3-3), and minimum 6 months after acute COVID-19 were included. The most common symptoms were weakness (75.33%), fever (74.03%), cough (51.95%), and loss of appetite (48.05%). Thirty-three patients were hospitalized; none required invasive ventilation therapy, but 16 required oxygen support. The treatment of COVID-19 included antibiotics (38.96%), thromboprophylaxis (25.97%), and nonsteroidal anti-inflammatory drugs, or paracetamol (25.97%). RESULTS: The median (IQR) values of serum creatinine 3 months before the onset and 6 months after COVID-19 were 1.25 (0.98-1.86) and 1.26 (1.03-1.78) mg/dL (nonsignificant difference); in strata analysis, there were also no differences with regards to patients with higher and lower comorbidity (3 < Charlson Comorbidity Index < 3) and fragility (3 < Fragility Score < 3). Furthermore, creatinine concentration in KTRs and controls did not differ. CONCLUSIONS: In the group of KTRs with a mild course of COVID-19, no negative impact of the infection on graft function was observed 6 months after transplantation.

Local and Systemic Immunity Are Impaired in End-Stage-Renal-Disease Patients Treated With Hemodialysis, Peritoneal Dialysis and Kidney Transplant Recipients Immunized With BNT162b2 Pfizer-BioNTech SARS-CoV-2 Vaccine.

Vaccination against COVID-19 in patients with end-stage renal disease (ESRD) on replacement therapy and kidney transplant recipients (KTRs) is particularly important due to the high mortality rate. Here, we tested the local and systemic immunity to the novel Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) in ESRD, KTR patients, and healthy individuals (150 subjects). The ESRD group was divided into: hemodialysis (HD) and peritoneal dialysis (PD). We investigated the local and systemic immunity based on anti-N (nucleoprotein) and anti-S (spike1/2) Immunoglobulin A (IgA) and Immunoglobulin G (IgG) antibodies, respectively. Additionally, we performed an Interferon gamma (IFN-γ) release test Interferon-gamma release assay (IGRA) to monitor the cellular component of vaccine response. The control group had the highest level of anti-S IgG antibodies (153/2,080 binding antibody units (BAU)/ml) among all analyzed patients after the 1st and 2nd dose, respectively. The HD group (48/926 BAU/ml) had a diminished antibody level compared to PD (93/1,607 BAU/ml). Moreover, the seroconversion rate after the 1st dose was lower in HD than PD (56% vs. 86%). KTRs had extremely low seroconversion (33%). IgA-mediated immunity was the most effective in the control group, while other patients had diminished IgA production. We observed a lower percentage of vaccine responders based on the IFN-γ level in all research participants (100% vs. 85% in control, 100% vs. 80% in PD, 97% vs. 64% in HD). 63% of seropositive KTRs had a positive IGRA, while 28% of seronegative patients produced IFN-γ. Collectively, PD patients had the strongest response among ESRD patients. Two doses of the Pfizer vaccine are ineffective, especially in HD and KTRs. A closer investigation of ESRD and KTRs is required to set the COVID-19 vaccine clinical guidance. Clinical Trial Registration Number: www.ClinicalTrials.gov, identifier: NCT04 905 862.

Waning Humoral Response after COVID-19 mRNA Vaccination in Maintenance Dialysis Patients and Recovery after a Complementary Third Dose.

The aim of this study was to analyze the waning of anti-spike (S) antibodies after mRNA vaccination against COVID-19 in maintenance dialysis patients, and to assess the safety and effectiveness of the complementary third dose. This was a prospective, longitudinal study in which we analyzed the kinetics of antibodies up to six months after a two-dose vaccination (first protocol) in infection-naïve dialysis patients (IN-Ds), previously infected dialysis patients (PI-Ds) and subjects without chronic kidney disease (the controls), as well as their humoral response to the third dose of the same mRNA vaccine (second protocol). The respective reduction in antibody titer after 3 and 6 months by 82.9% and 93.03% in IN-Ds (n = 109), 73.4% and 93.36% in PI-Ds (n = 32) and 75.5% and 88.8% in the controls (n = 20) was demonstrated. Consequently, a protective antibody titer above 141 BAU/mL was found in only 47.7% and 23.8% of IN-Ds after 3 and 6 months, respectively. After the third vaccine dose, a significant increase in antibody titer was observed in all groups, with increases by a factor of ×51.6 in IN-Ds, ×30.1 in the controls and ×8.4 in PI-Ds. The median antibody titer after the third dose differed significantly between groups, and was the highest in PI-Ds: PI-Ds, 9090 (3300−15,000) BAU/mL; the controls, 6945 (2130−11,800); IN-Ds, 3715 (1470−7325) (p < 0.001). In conclusion, we observed similar degrees of antibody waning in all patients. After 3 months, over half of the infection-naïve dialysis patients had a very low antibody titer, and almost twenty percent of them had no antibodies at all. The humoral response to the third dose was very good, raising their titer of antibodies to a higher level than those in the general population who have received the primary two-dose scheme. The results support the administration of a complementary third dose of the mRNA vaccine for dialysis patients as soon as possible.

Angiotensin Converting Enzyme Inhibitors May Increase While Active Vitamin D May Decrease the Risk of Severe Pneumonia in SARS-CoV-2 Infected Patients with Chronic Kidney Disease on Maintenance Hemodialysis.

The group most at risk of death due to COVID-19 are patients on maintenance hemodialysis (HD). The study aims to describe the clinical course of the early phase of SARS-CoV-2 infection and find predictors of the development of COVID-19 severe pneumonia in this population. This is a case series of HD nonvaccinated patients with COVID-19 stratified into mild pneumonia and severe pneumonia group according to the chest computed tomography (CT) pneumonia total severity score (TSS) on admission. Epidemiological, demographic, clinical, and laboratory data were obtained from hospital records. 85 HD patients with a mean age of 69.74 (13.19) years and dialysis vintage of 38 (14-84) months were included. On admission, 29.14% of patients had no symptoms, 70.59% reported fatigue followed by fever-44.71%, shortness of breath-40.0%, and cough-30.59%. 20% of the patients had finger oxygen saturation less than 90%. In 28.81% of patients, pulmonary parenchyma was involved in at least 25%. The factors associated with severe pneumonia include fever, low oxygen saturation and arterial partial pressure of oxygen, increased C-reactive protein and ferritin serum levels, low blood count of lymphocytes as well as chronic treatment with angiotensin converting enzyme inhibitors; while the chronic active vitamin D treatment was associated with mild pneumonia. In conclusion, even though nearly one-third of the patients were completely asymptomatic, while the remaining usually reported only single symptoms, a large percentage of them had extensive inflammatory changes at diagnosis with SARS-CoV-2 infection. We identified potential predictors of severe pneumonia, which might help individualize pharmacological treatment and improve clinical outcomes.

Short-term Effects of Losartan on Cardiovascular Risk and Allograft Injury Biomarkers in Kidney Transplant Recipients.

BACKGROUND: There is a controversy over the renoprotective and cardioprotective effects of renin-angiotensin-aldosterone system blockade in kidney transplant recipients (KTRs). The aim of the study was to evaluate the short-term effects of losartan on allograft injury, cardiovascular risk biomarkers and safety of the treatment in KTRs. METHODS: An interim analysis of a prospective, open, multicenter, controlled clinical trial CELART (Cardiovascular Effects of Losartan After Renal Transplantation) was performed. KTRs were allocated to losartan (L) 50 to 100 mg or standard hypotensive treatment (ST) group to reach target blood pressure (BP) <140/90 mm Hg. The short-term effects of the therapy were evaluated after 6 months: estimated glomerular filtration rate (eGFR), albuminuria, the intrarenal fibrosis biomarkers: urine excretion of transforming growth factor ß-1 (TGFß-1) and procollagen type III amino terminal propeptide (PIIINP), cardiac biomarker: serum concentration of N-terminal-pro-B-type natriuretic peptide (NT-proBNP), 24-hour ambulatory BP measurement, and hemoglobin and potassium concentrations. RESULTS: At baseline the groups did not differ with respect to age, primary nephropathy, comorbidity, immunosuppressive therapy, albuminuria, and graft function. A total of 61 (L group) and 73 (ST group) patients reached the target BP and completed protocol at 6 months. After 6 months of therapy there were no significant differences in changes of eGFR, albuminuria, hemoglobin and potassium concentrations, urine excretion of PIIINP, and TGFß-1 between groups. There was a trend in the L group to decrease the concentration of serum NT-proBNP. CONCLUSIONS: Losartan shows minimal adverse effects and no influence on graft function and biomarkers of graft fibrosis. It may have a positive effect on cardiovascular risk in KTRs. Further interim analyses of the CELART study will be conducted.