Analysis of the correlation between hypercholesterolemia and increased Cardiovascular Morbidity and Mortality among Adult Kidney Transplant Recipients.

INTRODUCTION: The correlation between hypercholesterolemia and cardiovascular disease in kidney transplant recipients (KTR) remains uncertain. We sought to characterize the association between abnormal cholesterol profiles and cardiovascular morbidity and mortality in this unique population. METHODS: This retrospective cohort study was conducted at a single center and included all adult KTR, transplanted between January 2005 and April 2014. The primary outcome was Major Adverse Cardiovascular Events (MACE) while the secondary outcome was the composite outcome of MACE and all-cause mortality. Exposure to abnormal cholesterol levels was calculated using a time-weighted average (TWA) calculation. MACE and mortality risk were analyzed using a multivariate time varying Cox model. RESULTS: The final cohort comprised 737 KTR, with a median follow-up of 2920 days. A total of 126 patients (17.1%) experienced MACE. High LDL-C levels and MACE risk were correlated by multivariate analysis (HR 1.008 per mg/dl, 95%CI 1.001 - 1.016), while low HDL-C levels were not significantly associated with MACE (HR 0.992 per mg/dl, 95%CI 0.976 - 1.009). A higher LDL-C/HDL-C ratio was significantly associated with an increased risk of MACE in multivariate analyses (HR 1.502 per unit, 95%CI 1.147-1.968), and also correlated with the composite outcome (HR 1.35 per unit, 95%CI 1.06 - 1.71). CONCLUSIONS: A high LDL-C /HDL-C ratio is predictive of an increased risk of cardiovascular morbidity and mortality in kidney transplant recipients. These findings emphasize the significance of the LDL-C/HDL-C ratio as a valuable marker of cardiovascular risk and support current recommendations to improve hypercholesterolemia in this high-risk group.

The Number of Episodes of Subtherapeutic Tacrolimus Blood Level Is Independently Associated With Reduced Kidney Graft Survival.

BACKGROUND: Tacrolimus blood level variability is associated with reduced graft survival among kidney transplant recipients. To date, no practical approach for reducing variability has been validated. We defined specific tacrolimus blood level patterns correlated with variability and evaluated their independent association with reduced graft survival. METHODS: In this single-center retrospective study, we predefined 12 patterns that exhibited correlation with high tacrolimus blood level variability. Subsequently, we utilized a multivariate Cox proportional hazard model, in conjunction with the Akaike information criteria, to evaluate the association between the predefined patterns and decreased graft survival. RESULTS: Our cohort included 1305 kidney transplant recipients. The primary outcome of this trial was graft loss, defined as the initiation of chronic dialysis or the need for retransplantation. The secondary outcome was the combination of death-censored graft loss and death with a functioning graft. During the study's follow-up period, there were 131 events of graft loss. The number of episodes of subtherapeutic tacrolimus level during the first-year posttransplantation was significantly associated with graft loss (HR 1.208 per episode, 95% CI 1.075-1.356, p = 0.001) and significantly improved the relative likelihood of the model compared to the multivariate model as demonstrated by the delta AIC value (8.256, p = 0.016). CONCLUSION: In addition to increased tacrolimus blood level variability, the number of episodes of subtherapeutic tacrolimus levels is independently associated with decreased graft survival among kidney transplant recipients.

Long-Term Graft and Patient Survival After Re-Transplantation.

BACKGROUND Kidney transplant recipients have higher life expectancy but may require subsequent transplantations, raising ethical concerns regarding organ allocation. We assessed the safety of multiple kidney transplants through long-term follow-up. MATERIAL AND METHODS A retrospective cohort study was conducted at a single center, categorizing patients based on the number of kidney transplantations received. The primary outcome was the composite of death-censored graft failure and overall mortality. The secondary outcome was death-censored graft failure. RESULTS Between 2000 and 2019, our center performed 2152 kidney transplantations. Patients were divided into 3 groups: A (1 transplant; n=1850), B (2 transplants; n=285), and C (3 or more transplants; n=75). Group C patients were younger, had fewer comorbidities, and received more aggressive induction therapy. The primary outcomes, including death-censored graft loss and overall mortality, showed similar rates across groups (A: 21.3%, B: 25.2%, C: 21.7%, p=0.068). However, the secondary outcome of death-censored graft failure alone was significantly lower in group A compared to the other groups. No significant difference was observed between groups B and C (8% vs 16% and 13%, respectively, p=0.001, p=0.845). Multivariate analysis identified having a living donor as the strongest predictor of patient and graft survival in all study groups. CONCLUSIONS Graft and patient survival rates were similar between first and multiple transplant recipients. Multiple transplant recipients had lower death-censored graft failure risk compared to first transplant recipients. However, the risk did not differ among second and subsequent transplant recipients. Younger patients, especially those with a living donor, should be considered for repeat kidney transplantation.

The association between hydrochlorothiazide use and non-melanoma skin cancer in kidney transplant recipients.

Background: hydrochlorothiazide (HCTZ) diuretics were correlated with an increased risk of non-melanoma skin cancer (NMSC) and melanoma in the general population. Information is a scarce regarding this effect in kidney transplant recipients who are at increased risk of skin malignancies under immunosuppression. Methods: Single-center retrospective analysis of adult kidney transplant recipients between 1 January 2010 and 31 December 2015. The primary outcome of the study was the first diagnosis of skin cancer that was removed and pathologically analyzed. Exposure to thiazides was defined as HCTZ use daily for at least one year at a dose of 12.5 mg. Results: Among 520 kidney transplant recipients, 50 (9.4%) were treated with HCTZ. During a median follow-up of 9.8 years, 67 patients underwent surgical removal and pathological analysis of at least one skin cancer. Exposure to HCTZ during the 3 years following transplantation was associated with an increased risk of skin cancer (P = 0.004). In a multivariate model, there was a significant association between HCTZ exposure and NMSC (HR 2.54, 95%CI 1.26-5.15, P = 0.007). There was a higher rate of basal cell carcinoma with HCTZ exposure, according to both univariate and multivariate analyses (HR 2.61, 95%CI 1.06-6.43, P = 0.037) and (HR 3.03, 95%CI 1.22-7.55, P = 0.017, respectively). However, no significant association was observed between HCTZ exposure and squamous cell carcinoma. Conclusions: These findings suggest a benefit of increased frequency of dermatologist inspection in kidney transplant recipients receiving HCTZ especially in increased ultraviolet exposure area.

Lower Incidence of Hypoglycemia With Angiotensin Receptor Blocker Versus ACE Inhibitor Therapy in People With or Without Diabetes.

This article describes a study examining the association between treatment with ACE inhibitors or angiotensin receptor blockers (ARBs) and incident hypoglycemia in patients with or without diabetes who were admitted to the internal medicine departments of a tertiary hospital in the Tel Aviv district of Israel. The authors found that treatment with ARBs, but not ACE inhibitors, compared with treatment with neither, was associated with a reduced risk of hypoglycemia regardless of diabetes status.

Improvement in Echocardiographic Indexes of Systolic Heart Failure Post-Kidney Transplantation: A Retrospective Analysis.

INTRODUCTION: End-stage renal disease is a major risk factor for cardiovascular morbidity and mortality, which can be partially eliminated by kidney transplantation. Systolic heart failure might be considered contraindication for kidney transplant, although some patients demonstrate myocardial recovery post-transplant. We aimed to identify and characterize the phenomenon of reverse myocardial remodeling in kidney transplanted patients. METHODS: The study is a retrospective cohort of patients undergoing kidney transplants between 2016 and 2019 (n = 604) at Rabin Medical Center. Patients were assessed according to availability of two echocardiographic examinations: pre- and post-kidney transplant. The change in estimated ejection fraction (EF) and possible predictors of myocardial recovery were examined. RESULTS: Data of 293 patients was available for the final analysis. Eighty-one (28%) patients had a LVEF improvement equal to or above 5%, whereas 36 (12%) patients had a LVEF improvement of 10% or more post-transplantation. Twenty-five patients (8.5%) had moderate or severe systolic heart failure with LVEF reduced to 40% or less at baseline. 13 of them (52%) had a LVEF improvement of ≥5%, and 10 patients (40%) had an improvement of ≥10% in their EF. Cox regression analyses identified female gender as the only independent variable associated with LVEF improvement of at least 10%. CONCLUSION: Renal transplantation might lead to improved LV systolic function in some patients.

The Importance of Early Diagnosis and Intervention in Chronic Kidney Disease: Calls-to-Action from Nephrologists Based Mainly in Central/Eastern Europe.

BACKGROUND: Chronic kidney disease (CKD) has a global prevalence of 9.1-13.4%. Comorbidities are abundant and may cause and affect CKD. Cardiovascular disease strongly correlates with CKD, increasing the burden of both diseases. SUMMARY: As a group of 15 clinical nephrologists primarily practicing in 12 Central/Eastern European countries, as well as Israel and Kazakhstan, herein we review the significant unmet needs for patients with CKD and recommend several key calls-to-action. Early diagnosis and treatment are imperative to ensure optimal outcomes for patients with CKD, with the potential to greatly reduce both morbidity and mortality. Lack of awareness of CKD, substandard indicators of kidney function, suboptimal screening rates, and geographical disparities in reimbursement often hamper access to effective care. KEY MESSAGES: Our key calls-to-action to address these unmet needs, thus improving the standard of care for patients with CKD, are the following: increase disease awareness, such as through education; encourage provision of financial support for patients; develop screening algorithms; revisit primary care physician referral practices; and create epidemiological databases that rectify the paucity of data on early-stage disease. By focusing attention on early detection, diagnosis, and treatment of high-risk and early-stage CKD populations, we aim to reduce the burdens, progression, and mortality of CKD.

Multi-phasic eGFR trajectory during follow up and long-term graft failure after kidney transplantation.

BACKGROUND: The prevailing assumption is that following kidney transplantation the pattern of kidney function decline is consistent. Nevertheless, numerous factors leading to graft loss may emerge, altering the trajectory of kidney function. In this study, we aim to assess alterations in estimated glomerular filtration rate (eGFR) trajectory over an extended period of follow-up and examine its correlation with graft survival. METHODS: We calculated eGFR using all creatinine values available from 1-year post transplantation to the end of follow-up. For pattern analysis, we used a piecewise linear model. RESULTS: Nine hundred eighty-eight patients were included in the study. After a median follow-up of 5.2 years, 297 (30.1%) patients had a multi-phasic eGFR trajectory. Change in eGFR trajectory was associated with increased risk for graft failure (HR 7.15, 95% CI 5.17-9.89, p < .001), longer follow-up time, younger age, longer cold ischemia time, high prevalence of acute rejection, longer hospitalization and a lower initial eGFR. Of the 988 patients included in the study, 494 (50.0%) had a mono-phasic stable trajectory, 197 (19.9%) had a mono-phasic decreasing trajectory, 184 (18.6%) had bi-phasic decreasing trajectory (initial stability and then decline, 46(4.7%) had a bi-phasic stabilized (initial decline and then stabilization) and 67(6.8%) had a more complex trajectory (tri-phasic). Out of the total 144 patients who experienced graft loss, the predominant pattern was a bi-phasic decline characterized by a bi-linear trajectory (66 events, 45.8%). CONCLUSIONS: Changes in eGFR trajectory during long-term follow-up can serve as a valuable tool for assessing the underlying mechanisms contributing to graft loss.

The Humoral Response to SARS-CoV-2 Vaccine in Hemodialysis Patients Is Correlated with Nutritional Status.

Hemodialysis patients are highly susceptible to poor nutritional status. Our objective was to investigate whether poor nutritional status during mRNA-SARS-CoV-2 vaccination is correlated with impaired vaccine responses. This retrospective study was conducted in two hospital-based dialysis units. The nutritional status of hemodialysis patients was assessed, using a malnutrition inflammation score (MIS) at the time of their first BNT162b2 vaccine dose. One month after the second vaccine dose, we performed a quantitative assessment of antibodies against the spike protein (anti-S1 IgG). A total of 115 hemodialysis patients, with an average age of 72 were enrolled in the study. Among them, 39 (33.9%) were female, and 67 (58.2%) had diabetes mellitus. In 43/115 (37.4%) patients, moderate to severe malnutrition (MIS > 5) was detected. Comparatively, malnourished patients showed a lower log-transformed mean level of anti-S1 IgG compared to those with normal nutrition (2.91 ± 0.83 vs. 3.25 ± 0.72, respectively, p = 0.024). In a multivariable analysis that adjusted for age, sex, and KT/V, the nutritional status assessed by an MIS remained inversely associated with an anti-S1 IgG response [B; -0.066 (-0.117 to -0.015)]. In conclusion, moderate to severe malnutrition in hemodialysis patients is associated with reduced humoral responses to BNT162b2 vaccination.

Bariatric Surgery in Severely Obese Kidney Donors Before Kidney Transplantation: A Retrospective Study.

BACKGROUND: Bariatric surgery (BS) is the optimal approach for sustained weight loss and may alter donation candidacy in potential donors with obesity. We evaluated the long-term effects of nephrectomy after BS on metabolic profile, including body mass index, serum lipids and diabetes, and kidney function of donors. METHODS: This was a single-center retrospective study. Live kidney donors who underwent BS before nephrectomy were matched for age, gender, and body mass index with patients who underwent BS alone and with donors who underwent nephrectomy alone. Estimated glomerular filtration rate (eGFR) was calculated according to Chronic Kidney Disease Epidemiology Collaboration and adjusted to individual body surface area to create absolute eGFR. RESULTS: Twenty-three patients who underwent BS before kidney donation were matched to 46 controls who underwent BS alone. At the last follow-up, the study group showed significantly worse lipid profile with low-density lipoprotein of 115 ± 25 mg/dL versus the control group with low-density lipoprotein of 99 ± 29 mg/dL ( P = 0.036) and mean total cholesterol of 191 ± 32 versus 174 ± 33 mg/dL ( P = 0.046). The second control group of matched nonobese kidney donors (n = 72) had similar serum creatinine, eGFR, and absolute eGFR as the study group before nephrectomy and 1 y after the procedure. At the end of follow-up, the study group had significantly higher absolute eGFR compared with the control group (86 ± 21 versus 76 ± 18 mL/min; P = 0.02) and similar serum creatinine and eGFR. CONCLUSIONS: BS before live kidney donation is a safe procedure that could increase the donor pool and improve their health in the long run. Donors should be encouraged to maintain their weight and avoid adverse lipid profile and hyperfiltration.

Acute Kidney Injury and Hair-Straightening Products: A Case Series.

RATIONALE & OBJECTIVE: Keratin-based hair-straightening treatment is a popular hair-styling method. The majority of keratin-based hair-straightening products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible, and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe acute kidney injury (AKI) following use of hair-straightening treatment in Israel during the past several years. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 26 patients from 14 medical centers in Israel who experienced severe AKI and reported prior treatment with hair-straightening products in 2019-2022. FINDINGS: The 26 patients described had a median age of 28.5 (range, 14-58) years and experienced severe AKI following a hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients experienced a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies, which demonstrated intratubular calcium oxalate deposition in 6 and microcalcification in tubular cells in 1. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in 4 cases. Three patients required temporary dialysis. LIMITATIONS: Retrospective uncontrolled study, small number of kidney biopsies. CONCLUSIONS: This series describes cases of AKI with prior exposure to hair-straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential underrecognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.

Novel insights in classic versus relative glomerular hyperfiltration and implications on pharmacotherapy.

PURPOSE OF REVIEW: Glomerular filtration rate (GFR) assessment and its estimation (eGFR) is a long-lasting challenge in medicine and public health. Current eGFR formulae are indexed for standardized body surface area (BSA) of 1.73 m2, ignoring persons and populations wherein the ratio of BSA or metabolic rate to nephron number might be different, due to increased BSA, increased metabolic rate or reduced nephron number. These equations are based on creatinine, cystatin C or a combination of the two, which adds another confounder to eGFR assessment. Unusually high GFR values, also known as renal hyperfiltration, have not been well defined under these equations. RECENT FINDINGS: Special conditions such as solitary kidney in kidney donors, high dietary protein intake, obesity and diabetes are often associated with renal hyperfiltration and amenable to errors in GFR estimation. In all hyperfiltration types, there is an increased intraglomerular pressure that can be physiologic, but its persistence over time is detrimental to glomerulus leading to progressive glomerular damage and renal fibrosis. Hyperfiltration might be underdiagnosed due to BSA standardization embedded in the formula. Hence, timely intervention is delayed. Reducing intraglomerular pressure in diabetes can be achieved by SGLT2 inhibitors or low protein diet to reverse the glomerulopathy process. SUMMARY: Accurate identification of glomerular hyperfiltration as a pre-CKD condition needs accurate estimation of GFR in the above normal range should establish a threshold for timely intervention.

Humoral Response to the Third Dose of BNT162b2 COVID-19 Vaccine among Hemodialysis Patients.

BACKGROUND: Hemodialysis patients are at high risk for severe COVID-19 disease. Despite a high early seropositivity rate, dialysis patients mount a dampened immune response following two doses of an mRNA vaccine. This study aimed to evaluate the serologic response to a booster dose of BNT162b2 vaccine, 6 months after the second dose, among hemodialysis patients. METHODS: This prospective study included 80 hemodialysis patients and 56 healthcare workers serving as controls. Serologic samples were evaluated before and ∼3 weeks after the third vaccine dose. The primary outcomes were the seropositivity rate and the log-transformed anti-SARS-COV-2 S1 (RBD) IgG as a continuous variable after the third dose. Secondary outcomes were the proportion of participants with "high response," defined as antibody levels >1,000 AU/mL, and "robust response," defined as antibody levels >4,160 AU/mL, according to prespecified cutoff values associated with neutralizing antibodies. Univariate and multivariate analyses were conducted to identify predictors of antibody response. RESULTS: Among 80 hemodialysis patients, seropositivity rates improved from 78% (62/80) before the third dose, up to 96% (77/80) after the booster dose. The S1-RBD log-transformed antibody level increased significantly following the third dose from 2.15 ± 0.75 to 3.99 ± 0.83 compared with 2.65 ± 0.4 to 4.31 ± 0.42 in the control group. Among the hemodialysis patients, 88% (70/80) became "high responders" (>1,000 AU/mL), and of these, 79% (63/80) mounted a "robust response" (>4,160 AU/mL). Baseline antibody level, dialysis therapy, and hypoalbuminemia were independent predictors of impaired antibody response. CONCLUSIONS: A third dose of BNT162b2 COVID-19 vaccine, 6 months after the standard two-dose vaccination regimen, substantially improved humoral response in hemodialysis patients.

Exposure to tacrolimus trough levels below 6 ng/ml during the first year is associated with inferior kidney graft survival.

BACKGROUND: Accumulating data indicate that sub-therapeutic levels of tacrolimus are associated with long-term kidney graft loss. However, elevated doses increase the risk of infection and drug toxicity, which also threaten graft and patient longevity. We sought to determine the minimal tacrolimus level required to maintain graft survival. METHODS: We conducted a single-center historical cohort study. The first-year post-transplant exposure time was calculated for each of the five tacrolimus trough level intervals. This measure was adjusted to the exposure time below a given interval level, allowing us to define the threshold for the optimal tacrolimus level as the upper limit of the interval. We then determined the association between the adjusted exposure time at each tacrolimus level interval and our primary outcome, death-censored graft loss. RESULTS: One thousand four hundred and seventeen patients with a median follow-up of 5.3 years were included in the final cohort. The tacrolimus level interval of 5-6 ng/ml was the highest interval, which demonstrated a statistically significant association between adjusted exposure time and increased risk of graft loss (HR 1.58, per log days, p = .002). Cumulative exposure time above 14 days with a tacrolimus level below 6 ng/ml was associated with an increased rate of graft loss in most studied subgroups, except for recipients with pre transplant diabetes. CONCLUSIONS: Maintaining tacrolimus levels above 6 ng/ml during the first-year post-transplant might improve kidney graft survival.

Changes in Serum Creatinine May Cause Hypoglycemia among Non-Critically Ill Patients Admitted to Internal Medicine Units.

Background: The association between changes in serum creatinine levels and hypoglycemia during hospitalization was investigated. Methods: This was a retrospective analysis of medical charts. Patients were categorized as having significant change in creatinine (SCIC) when serum creatinine levels rose or dropped ≥ 0.3 mg/dL from admission values at any time during their hospitalization. Patients were considered hypoglycemic if they had at least one documented glucose level ≤ 70 mg/dL during the hospitalization. Multiple logistic, linear and Cox regression analyses were used to ascertain the association between incident SCIC, severity and timing with incident hypoglycemia. Results: Included were 25,400 (mean age 69.9 ± 18.0, 49.3% were males). The rate of SCIC was 22.2%, and 62.2% of them were diagnosed upon admission. Patients with SCIC had a higher incidence of hypoglycemia compared to patients without (13.1% vs. 4.1%, respectively, p < 0.001). Patients with SCIC had an increased risk of hypoglycemia (OR 1.853, 95% CI 1.586−2.166, p < 0.001). The magnitude of SCIC was associated with the incidence (OR 1.316, 95% CI 1.197−1.447, p < 0.001) and the number of events (HR 0.054, 95% CI 0.021−0.087, p = 0.001). More than 60% of patients with hypoglycemia had their first event documented during days 0−6 after SCIC occurrence. Of those, the majority of events occurred on day 0−1, and the rate showed a gradual decrease throughout the first 5 days from SCIC occurrence. The results were similar for patients with and without DM. Conclusions: Changes in creatinine during hospitalization may cause hypoglycemia among patients admitted to internal medicine departments, regardless of DM status.

Plasma porphyrins among end stage renal disease patients and cutaneous symptoms- is there still an association?

Introduction: Several abnormalities of porphyrin metabolism leading to Porphyria Cutanea Tarda (PCT) have been described in early studies of End Stage Renal Disease (ESRD) patients, with a reported prevalence of 5-18%. We aimed to evaluate porphyrin levels and correlation to skin manifestations in modern dialysis era. Methods: The study cohort included adult hemodialysis patients from a single center tertiary medical center. All patients underwent a full skin examination, completed the Dermatology Life Quality Index questioner, and provided a blood sample for porphyrin levels assessment. Results: A total of 94 adult hemodialysis patients were recruited to the study. No clinical PCT was diagnosed. Porphyrin levels did not correlate with any clinical or dialysis quality parameters. Conclusions: In modern hemodialysis era, possibly due to improved porphyrins' metabolism and dialysis removal, PCT is much less prevalent among hemodialysis patients than previously reported in the past.

BNT162b2 vaccine effectiveness in chronic kidney disease patients-an observational study.

Background: Chronic kidney disease (CKD) is a risk factor for severe coronavirus disease 2019 (COVID-19). We aimed to evaluate the real-life effectiveness of the BNT162b2 messenger RNA vaccine for a range of outcomes in patients with CKD compared with matched controls. Methods: Data from Israel's largest healthcare organization were retrospectively used. Vaccinated CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2] and maintenance dialysis patients were matched to vaccinated controls without CKD (eGFR ≥60 ml/min/1.73 m2) according to demographic and clinical characteristics. Study outcomes included documented infection with severe acute respiratory syndrome coronavirus 2, symptomatic infection, COVID-19-related hospitalization, severe disease and death. Vaccine effectiveness was estimated as the risk ratio (RR) at days 7-28 following the second vaccine dose, using the Kaplan-Meier estimator. Effectiveness measures were also evaluated separately for various stages of CKD. Results: There were 67 861 CKD patients not treated with dialysis, 2606 hemodialysis (HD) patients and 70 467 matched controls. The risk of severe disease {RR 1.84 [95% confidence interval (CI) 0.95-2.67]} and death [RR 2.00 (95% CI 0.99-5.20)] was increased in nondialysis CKD patients compared with controls without CKD following vaccination. For the subgroup of patients with eGFR <30 ml/min/1.73 m2, the risk of severe disease and death was increased compared with controls [RR 6.42 (95% CI 1.85-17.51) and RR 8.81 (95% CI 1.63-13.81), respectively]. The risks for all study outcomes were increased in HD patients compared with controls. Conclusion: Two doses of the BNT162b2 vaccine were found to be less efficient for patients with eGFR <30 ml/min/1.73 m2. Risk in HD patients is increased for all outcomes. These results suggest prioritizing patients with eGFR <30 ml/min/1.73 m2 for booster shots, pre- and post-exposure prophylaxis and early COVID-19 therapy.

BNT162b2 Booster Vaccination Induced Immunity against SARS-CoV-2 Variants among Hemodialysis Patients.

Background: The emergence of new SARS-CoV-2 variants, which evade immunity, has raised the urgent need for multiple vaccine booster doses for vulnerable populations. In this study, we aimed to estimate the BNT162b2 booster effectiveness against the spread of coronavirus variants in a hemodialysis population. Methods: We compared humoral and cell-mediated immunity in 100 dialysis patients and 66 age-matched volunteers, before and 2-3 weeks following the first booster vaccine dose. Participants were assessed for anti-spike (RBD) antibody titer, neutralizing antibodies against B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants, spike-specific T-cell responses by FACS and infection outbreak after the first and second booster. Results: Anti-spike antibody titer was significantly increased following the booster, with reduced humoral and cellular response in the dialysis patients. Neutralizing antibody levels increased significantly after the booster dose, with an inferior effect (≤2 fold) against Omicron compared with the Delta variant. Furthermore, CD4+ and CD8+ T-cell activation by Delta spike protein was preserved in 70% of PBMCs from the dialysis patients. A second booster dose tended to reduce breakthrough infections in the dialysis patients. Conclusions: Until the release of an updated vaccine, BNT162b2 booster doses will improve the humoral and cell-mediated immunity against variants. These findings support the importance of repetitive booster doses for hemodialysis patients.