Improvement in Echocardiographic Indexes of Systolic Heart Failure Post Kidney Transplantation - a retrospective analysis.

INTRODUCTION: End-stage renal disease (ESRD) is a major risk factor for cardiovascular morbidity and mortality, which can be partially eliminated by kidney transplantation. Systolic heart failure might be considered as contraindication for kidney transplant although some patients demonstrate myocardial recovery post-transplant. We aim to identify and characterize the phenomenon of reverse myocardial remodelling in kidney transplanted patients. METHODS: The study is a retrospective cohort of patients undergoing kidney transplant between 2016-2019 (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 or above 5%, whereas 36 (12%) patients had a LVEF improvement 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.

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.

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.

Absence of hemoglobin increase is associated with reduced graft survival after kidney transplantation.

BACKGROUND: Anemia is prevalent following kidney transplantation and is associated with reduced graft survival. The association between temporal changes in hemoglobin (Hb) level at the early post-transplant period and graft survival is unknown. PATIENTS AND METHODS: The study cohort included consecutive patients included in a single center transplantation registry between January 2002 and December 2016. Temporal changes in Hb values during the first 90 days after the transplantation were evaluated by piecewise linear regression model. Significant Hb increase rate was defined as an increase of .5 gram/deciliter/month. Patients were divided into groups according to the presence of significant Hb increase. The primary outcome was death-censored graft failure. RESULTS: Of 946 patients included in the study cohort, 831 (87.8%) had at least one interval of Hb increase, and 115 (12.2%) had no Hb increase. The absence of Hb increase was associated with an elevated risk of death censored graft failure by univariate (HR 2.9, 95% CI 1.88-4.49, P < .001) and multivariate (HR 2.47, 95% CI 1.48-4.12, P = .001) analyses. The timing and rate of Hb increase had no association with the main outcome. CONCLUSIONS: Lack of Hb increase during the early post-transplant period is associated with an increased risk of graft loss.

Immune Response to Third Dose BNT162b2 COVID-19 Vaccine Among Kidney Transplant Recipients-A Prospective Study.

Immune response to two SARS-CoV-2 mRNA vaccine doses among kidney transplant recipients (KTRs) is limited. We aimed to evaluate humoral and cellular response to a third BNT162b2 dose. In this prospective study, 190 KTRs were evaluated before and ∼3 weeks after the third vaccine dose. The primary outcomes were anti-spike antibody level >4160 AU/ml (neutralization-associated cutoff) and any seropositivity. Univariate and multivariate analyses were conducted to identify variables associated with antibody response. T-cell response was evaluated in a subset of participants. Results were compared to a control group of 56 healthcare workers. Among KTRs, we found a seropositivity rate of 70% (133/190) after the third dose (37%, 70/190, after the second vaccine dose); and 27% (52/190) achieved levels above 4160 AU/ml after the third dose, compared to 93% of controls. Variables associated with antibody response included higher antibody levels after the second dose (odds ratio [OR] 30.8 per log AU/ml, 95% confidence interval [CI]11-86.4, p < 0.001); and discontinuation of antimetabolite prior to vaccination (OR 9.1,95% CI 1.8-46.5, p = 0.008). T-cell response was demonstrated in 13% (7/53). In conclusion, third dose BNT162b2 improved immune response among KTRs, however 30% still remained seronegative. Pre-vaccination temporary immunosuppression reduction improved antibody response.

The Effect of Tafamidis on Circulating Endothelial Progenitor Cells in Patients with Transthyretin Cardiac Amyloidosis.

AIMS: Endothelial microvascular dysfunction is a known mechanism of vascular pathology in cardiac amyloidosis (CA). Scientific evidence regarding the possible protective role of the amyloid transthyretin (ATTR) stabilizer, tafamidis, is lacking. Circulating endothelial progenitor cells (cEPCs) have an important role in the process of vascular repair. We aimed to examine the effect of tafamidis on cEPCs. METHODS AND RESULTS: Study population included patients with ATTR-CA. cEPCs were assessed using flow cytometry by the expression of CD34(+)/CD133(+) and vascular endothelial growth factor receptor (VEGFR)-2(+) and by the formation of colony-forming units (CFUs) and production of VEGF. Tests were repeated at pre-specified time-points up to 12 months following the initiation of tafamidis. Included were 18 ATTR-CA patients at a median age of 77 (IQR 71, 85) years and male predominance (n = 15, 83%). Following the initiation of tafamidis and during 12 months of drug treatment, there was a gradual increase in the levels of CD34(+)/VEGFR-2(+) (0.43 to 2.42% (IQR 1.53, 2.91)%, p = 0.002) and CD133(+)/VEGFR-2(+) (0.49 to 1.64% (IQR 0.97, 2.90)%, p = 0.004). Functionally, increase in EPCs-CFUs was microscopically evident following treatment with tafamidis (from 0.5 CFUs (IQR 0.0, 1.0) to 3.0 (IQR 1.3, 3.8) p < 0.001) with a concomitant increase in EPC's viability as demonstrated by an MTT assay (from 0.12 (IQR 0.03, 0.16) to 0.30 (IQR 0.18, 0.33), p < 0.001). VEGF levels increased following treatment (from 54 (IQR 52, 72) to 107 (IQR 62, 129) pg/ml, p = 0.039). CONCLUSIONS: Tafamidis induced the activation of the cEPCs pathway, possibly promoting endothelial repair in ATTR-CA.

Novel Protein to Phosphorous Ratio Score Predicts Mortality in Hemodialysis Patients.

OBJECTIVE: Lowering serum phosphorus in people on hemodialysis may improve their survival. However, prior studies have shown that restricting dietary protein intake, a major source of phosphorus, is associated with higher mortality. We hypothesized that a novel metric that incorporates both these values commensurately can improve survival prediction. METHODS: We used serum phosphorous and normalized protein catabolic rate (nPCR), a surrogate of dietary protein intake, to form a new metric R that was used to examine the associations with mortality in 63,016 people on hemodialysis (HD) of one year after treatment initiation. Survival models were adjusted for case-mix, malnutrition-inflammation cachexia syndrome (MICS), and residual kidney function (RKF). RESULTS: Individuals treated with hemodialysis were divided into five groups in accordance with R value. Group 1 included sick individuals with high phosphorous and low nPCR. Group 5 included individuals with low phosphorous and high nPCR. After 1-year follow-up, survival difference between the groups reflected R value, where an increase in R was associated with improved survival. The association of R with mortality was strengthened by adjustment in demographic variables and attenuated after adjustment to MICS. Mortality associations in accordance with R were not influenced by residual kidney function (RKF). CONCLUSION: The novel protein to phosphorus ratio score R predicts mortality in people on dialysis, probably reflecting both nutrition and inflammation state independent of RKF. The metric enables better phosphorus monitoring, although adequate dietary protein intake is ensured and may improve the prediction of outcomes in the clinical setting.

Low serum albumin levels predict short- and long-term mortality risk in patients hospitalised to general surgery wards.

BACKGROUND: Previous studies have reported conflicting results on the association between hypoalbuminaemia and morbidity and mortality in hospitalised patients. AIMS: To investigate the association of albumin levels on admission and change in levels during hospitalisation of patients in general surgery wards with hospitalisation outcomes. METHODS: Historical prospective data of patients hospitalised between January 2011 and December 2017. Albumin levels were classified as follows: marked hypoalbuminaemia (<2.5 mg/dL), mild hypoalbuminaemia (2.5-3.5 mg/dL), normal albumin (3.5-4.5 mg/dL) and hyperalbuminaemia (>4.5 mg/dL). Main outcomes were length of hospitalisation, 30-days and long-term mortality. RESULTS: The cohort included 17 930 patients (mean age 58 ± 20 years, 49% male). Most had normal albumin levels on admission (n = 11 087, 62%), 16% had mild hypoalbuminaemia (n = 2824) and 3% had marked hypoalbuminaemia (n = 529). Hyperalbuminaemia on admission was evident in 20% of the patients (n = 3490). Follow-up time was up to 7.2 years (median ± SD = 3 ± 2 years). Compared to 30-day mortality with normal albumin on admission (2%), mortality was higher with mild (9%) and marked hypoalbuminaemia (22%) and lower with hyperalbuminaemia (0.4%). The mortality rate at the end of follow up was 14% with normal albumin levels, and 35% and 58% with mild and marked hypoalbuminaemia respectively. Patients with hyperalbuminaemia on admission and before discharge had the best short- and long-term survival. This pattern was similar when analysed separately in different age groups. In patients with hypoalbuminaemia on admission, normalisation of albumin levels before discharge was associated with lower short- (12% vs 1%) and long-term mortality risk (42% vs 17%). CONCLUSIONS: Low albumin levels on admission to general surgery wards are associated with increased short- and long-term mortality. Normalisation of albumin levels before discharge was associated with lower mortality, compared to hypoalbuminaemia before discharge.

Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial.

BACKGROUND: Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited. METHODS: This was a randomized, multicenter, open-label, noninferiority trial. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 days (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative, or distant complications; and readmission or extended hospitalization (>14 days). The noninferiority margin was set at 10%. RESULTS: We included 604 patients (306 intervention, 298 control) between January 2013 and August 2017 in 3 centers in Israel and Italy. The source of the infection was urinary in 411 of 604 patients (68%); causative pathogens were mainly Enterobacteriaceae (543/604 [90%]). A 7-day difference in the median duration of covering antibiotics was achieved. The primary outcome occurred in 140 of 306 patients (45.8%) in the 7-day group vs 144 of 298 (48.3%) in the 14-day group (risk difference, -2.6% [95% confidence interval, -10.5% to 5.3%]). No significant differences were observed in all other outcomes and adverse events, except for a shorter time to return to baseline functional status in the short-course therapy arm. CONCLUSIONS: In patients hospitalized with gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was noninferior to 14 days. Reducing antibiotic treatment for uncomplicated gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention. CLINICAL TRIALS REGISTRATION: NCT01737320.

Diagnostic Accuracy of PCR Alone and Compared to Urinary Antigen Testing for Detection of Legionella spp.: a Systematic Review.

The diagnosis of Legionnaires' disease (LD) is based on the isolation of Legionella spp., a 4-fold rise in antibodies, a positive urinary antigen (UA), or direct immunofluorescence tests. PCR is not accepted as a diagnostic tool for LD. This systematic review assesses the diagnostic accuracy of PCR in various clinical samples with a direct comparison versus UA. We included prospective or retrospective cohort and case-control studies. Studies were included if they used the Centers for Disease Control and Prevention consensus definition criteria of LD or a similar one, assessed only patients with clinical pneumonia, and reported data for all true-positive, false-positive, true-negative, and false-negative results. Two reviewers abstracted data independently. Risk of bias was assessed using Quadas-2. Summary sensitivity and specificity values were estimated using a bivariate model and reported with a 95% confidence interval (CI). Thirty-eight studies were included. A total of 653 patients had confirmed LD, and 3,593 patients had pneumonia due to other pathogens. The methodological quality of the studies as assessed by the Quadas-2 tool was poor to fair. The summary sensitivity and specificity values for diagnosis of LD in respiratory samples were 97.4% (95% CI, 91.1% to 99.2%) and 98.6% (95% CI, 97.4% to 99.3%), respectively. These results were mainly unchanged by any covariates tested and subgroup analysis. The diagnostic performance of PCR in respiratory samples was much better than that of UA. Compared to UA, PCR in respiratory samples (especially in sputum samples or swabs) revealed a significant advantage in sensitivity and an additional diagnosis of 18% to 30% of LD cases. The diagnostic performance of PCR in respiratory samples was excellent and preferable to that of the UA. Results were independent on the covariate tested. PCR in respiratory samples should be regarded as a valid tool for the diagnosis of LD.

Glucagon-like Peptide 1 Receptor Agonists and Cardiovascular Outcomes in Solid Organ Transplant Recipients With Diabetes Mellitus.

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce cardiovascular events and mortality in type 2 diabetes. Limited data are available on diabetes treatment after solid organ transplantation. We aimed to explore the effect of GLP1-RAs on cardiovascular outcomes in transplanted recipients with diabetes. METHODS: We extracted data on adult transplant recipients (kidney, lungs, liver, heart) insured in a large health maintenance organization. Death-censored patients with diabetes treated with GLP1-RAs were matched with nonusers. The primary outcome was a composite of major cardiovascular events (MACEs): a nonfatal cardiac event (myocardial infarction, stable/unstable angina, coronary bypass, and coronary angiography), ischemic stroke and all-cause mortality. Secondary outcomes were MACE or peripheral vascular disease (MACE-PVD), and all-cause mortality. Safety outcomes included biliopancreatic adverse events. RESULTS: We included 318 patients (69% males, average age 58.3 ±â€…11.0 y) with a 3.1-y median follow-up. The incidence of MACE was 101 of 1000 patient-years in GLP1-RAs users compared with 134 of 1000 in controls (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.27-0.78). GLP1-RAs similarly reduced the risk of MACE-PVD (HR 0.53; 95% CI, 0.33-0.88) and the risk of all-cause mortality (HR 0.39; 95% CI, 0.18-0.84). Biliopancreatic adverse events occurred less in GLP1-RA users. CONCLUSIONS: Transplant recipients with diabetes who used GLP1-RAs had lower risks for MACE and all-cause mortality. These results may profoundly implicate the daily management of posttransplant recipients with diabetes, a population with a high prevalence of cardiometabolic risk factors and cardiovascular death. Transplant patients are usually excluded from randomized controlled trials and, hence might be undertreated with disease-modifying drugs. Larger prospective studies are needed in this unique population.

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.

Tricuspid Regurgitation and Kidney Transplant Recipient Outcomes.

Rationale & Objective: Kidney function can be adversely affected by significant tricuspid regurgitation (TR) owing to effects on cardiac output and systemic venous congestion. However, the impact of significant TR on short- and long-term kidney function following a kidney transplant remains uncertain. Study Design: Retrospective observational cohort. Setting & Participants: Kidney transplant recipients from a single center between 2016 and 2019. Exposure: Significant TR, defined by at least moderate regurgitation, on echocardiogram before kidney transplantation. Outcomes: Primary end points included the estimated glomerular filtration rate (eGFR) at the following 3 time points: 2 weeks, 3 months, and 1 year after transplantation. Secondary end points included major adverse cardiac events including nonfatal myocardial infarction, all-cause mortality, and hospitalization owing to cardiovascular disease. Analytical Approach: Propensity score matching was performed in 1:3 ratio between patients treated with significant TR and controls, within a caliper 0.05 standard deviation of the propensity score, to analyze for the primary end point. Results: Among 557 kidney transplant recipients, 26 (5%) exhibited significant TR pretransplantation. According to propensity score matching analysis, with 1:3 ratio between 24 patients with significant TR and 72 controls, the presence of significant TR was associated with a lower eGFR posttransplantation. Specifically, the mean eGFR was 41.2 mL/min/1.73 m2 compared to 53.3 mL/min/1.73 m2 at 2 weeks (P < 0.01), 50.0 mL/min/1.73 m2 versus 60.3 mL/min/1.73 m2 at 3 months (P < 0.01), and 49.4 mL/min/1.73 m2 versus 61.2 mL/min/1.73 m2 at 1 year (P < 0.01). Delayed graft function was observed in 41.7% of the patients with significant TR compared to 12.5% of those without significant TR (P < 0.01). No patients with significant TR required dialysis after 1 year. 1-year major adverse cardiac events were nonsignificantly higher among patients with significant TR (20.8% vs 8.1%; P = 0.16). Limitations: Retrospective design and relatively small TR population. Conclusions: The presence of significant TR among kidney transplant recipients was associated with a lower eGFR at 2 weeks, 3 months, and 1 year following transplant, although all remained dialysis independent at 1 year.

Significant tricuspid regurgitation (TR) is associated with increased mortality rates and kidney failure, but its impact on kidney transplant recipients is poorly investigated. We examined how significant TR diagnosed pretransplantation affects kidney function within the first posttransplant year in a retrospective cohort study. Among 24 patients with significant TR, there was a consistent pattern of lower kidney function at 2 weeks, 3 months, and 1 year following transplantation, compared to 72 matched controls based on a propensity score. Results were statistically significant at all time points within the first year after transplant. These findings suggest that selected individuals with significant TR are able to undergo successful kidney transplantation, although with worse kidney function following transplantation.

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.

Chronic Renal Failure and Cardiovascular Disease: A Comprehensive Appraisal.

Coronary artery disease is highly prevalent in patients with chronic kidney disease. The concomitant renal disease often poses a major challenge in decision making as symptoms, cardiac biomarkers and noninvasive studies for evaluation of myocardial ischemia have different sensitivity and specificity thresholds in this specific population. Moreover, the effectiveness and safety of intervention and medical treatment in those patients is of great doubt as most clinical studies exclude patients with advance CKD. In the present paper, we discuss and review the literature in the diagnosis, treatment and prevention of CAD in the acute and chronic setting, in patients with CKD.

Longevity of Humoral Response Six Months Following BNT162b2 Vaccine in Dialysis Patients.

Background: End-stage kidney disease substantially increases the risk of severe COVID-19. However, despite early robust immunogenicity of the mRNA-SARS-CoV-2 vaccination in patients with hemodialysis, the longevity of humoral response in this high-risk population is still unknown. Methods: A prospective cohort study aimed to evaluate the longevity of serologic response in patients with hemodialysis, compared with a control group, 6 months following the second dose of the BNT162b2 vaccine. We assessed antibody response by quantitative measurement of IgG antibodies against the receptor-binding domain of the Spike protein (anti-S1-RBD IgG). Study outcomes were defined as a seropositivity rate and log-transformed anti-S1-RBD IgG levels at 6 months, and the change in antibody levels between 3 and 6 months. Findings: The cohort included 104 patients with hemodialysis and 84 controls. At a median time of 184 days (IQR, 183-188) following the second dose of the vaccine, 83/104 (79.8%) patients with hemodialysis maintained seropositivity for the anti-S1-RBD IgG level compared to 83/84 (98.8%) in the control group (p < 0.001). The log-transformed antibody level was significantly lower in the hemodialysis group (2.23 ± 0.39 log AU/ml vs. 2.69 ± 0.65 log AU/ml, respectively, p < 0.001). Older age and hypoalbuminemia were the only variables that were found to be associated with reduced log-transformed antibody levels in univariate and multivariate analysis. There was no interaction between dialysis status and an antibody-level decline rate (p = 0.972). Conclusion: Among patients with hemodialysis, a seropositivity rate and anti-S1-RBD antibody titers were substantially reduced compared with a control group, at 6 months following the second dose of the BNT162b2 vaccine. These findings support the prioritization of patients with hemodialysis for a third "booster" dose.

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.

SARS-CoV-2 antibody dynamics among kidney transplant recipients 3 months after BNT162b2 vaccination: a prospective cohort study.

Data regarding immunogenicity of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among kidney transplant recipients in the months following vaccination are lacking. We aimed to investigate humoral immune response at 3-4 months post-vaccination among a cohort of kidney transplant recipients, compared with a control group of dialysis patients. Anti-spike antibodies were tested at 1 and 3-4 months after vaccination. Of 259 kidney transplant recipients tested at a median time of 110 days from second vaccine dose, 99 (38%) were seropositive, compared with 83% (101/122) of control patients. Younger age, better renal function and lower immunosuppression levels were associated with seropositivity. A total of 14% (13/94) of participants seropositive at 1 month became seronegative at follow-up and 11% (18/165) became seropositive. The latter were mainly individuals with higher antibody levels at 1 month. Antibody levels at 3-4 months were significantly reduced in both study groups, although the decline was more pronounced in the control group. Kidney transplant recipients present poor antibody response to mRNA SARS-CoV-2 vaccination, with only 38% seropositive at 3-4 months. Nevertheless, the decay in antibody response over time is modest, and some patients may present delayed response, reaching adequate antibody levels at 3-4 months. Low seropositivity rates in this group call for investigating other immunization strategies.

The prognostic value of pre-operative coronary evaluation in kidney transplanted patients.

Aims: Non-invasive coronary assessment using single-photon emission computerized tomography (SPECT) testing for potential cardiac ischemia is an essential part of the evaluation of kidney transplant candidates. We aimed to examine the prognostic value of preoperative SPECT test results in kidney transplanted patients. Methods and results: We retrospectively analyzed the pre-surgical nuclear SPECT test results in a registry of kidney transplanted patients. Follow-up at 1 month and 1 year recorded major adverse cardiac events (MACE) including non-fatal myocardial infarction, all-cause mortality and hospitalization due to cardiovascular disease following the renal transplantation. Of 577 patients available for analysis, 408 (70.9%) patients underwent nuclear SPECT test pre-transplant and 83 (20.3%) had abnormal results with either evidence of ischemia or infarct. A significantly higher incidence of post-operative MACE at 1 month was evident among patients with abnormal SPECT test compared to patients with no evidence of ischemia (10.8 vs. 4.3% respectively; P = 0.019). Differences were mostly derived from significantly increased rates of myocardial infarction events (8.4 vs. 1.8%; P = 0.002). Yet, MACE rate was not statistically different at 1 year (20.5 vs. 13.1%; P = 0.88). Importantly, the prognostic impact of an abnormal SPECT was significantly attenuated for all outcomes following multivariable adjusting for conventional cardiovascular risk factors and coronary revascularization. Conclusion: Pre-surgical cardiac risk assessment of kidney transplant candidates with nuclear SPECT test was found to be predictive of post-operative MACE, yet apparently, its prognostic value was significantly attenuated when adjusted for cardiac risk factors.

The Association Between Exposure to Low Magnesium Blood Levels After Renal Transplantation and Cardiovascular Morbidity and Mortality.

Background: Serum magnesium levels are associated with cardiovascular disease and all-cause mortality in the general population and chronic kidney disease patients, but the association between serum magnesium levels and cardiovascular risk after kidney transplantation is not established. We sought to evaluate whether exposure to low serum magnesium levels after renal transplantation is related to cardiovascular morbidity and mortality. Methods: We conducted a single center retrospective study that included all transplanted patients who had a functioning graft for at least 6 months after transplantation between January 2001 and December 2013. We calculated exposure to magnesium using time weighted average for serum magnesium levels, using all values available during the follow-up. Several statistical methods were used, including liner regression analysis, χ2 test, and multivariate Cox proportional hazard model. Results: Four hundred ninety-eight patients were included. Median follow-up was 5.26 years. High time weighted average of serum magnesium was associated with a hazard ratio of 1.94 for all-cause mortality and major cardiovascular outcome compared to low levels (95% CI 1.18-3.19, p = 0.009). The high quartile of time weighted average of serum magnesium was associated with death censored major cardiovascular outcome (hazard ratio 2.13, 95% CI 1.17-3.86, p = 0.013) in multivariate analysis. Conclusions: Exposure to low serum magnesium levels in renal transplant recipients was associated with a lower risk for all-cause mortality and major cardiovascular outcome. These findings contrast the higher risk found in the general population.