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.

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.

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.

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.

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.

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.

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.

Association between estimated GFR and incident hypoglycaemia during hospitalization.

BACKGROUND: Kidney function is a significant factor associated with increased incidence of hypoglycaemia, especially among patients with diabetes mellitus (DM). We here quantified the association between elevated creatinine and incident hypoglycaemia among patients admitted to internal medicine departments, with and without DM. METHODS: This is a retrospective cohort analysis study. Included were all patients discharged from internal medicine units between 2010 and 2013. Patients were excluded if creatinine levels rose or dropped more than 0.3 mg/dL during hospitalization. The CKD-EPI equation was used to calculate glomerular filtration rate (eGFR). Logistic regression analysis (backward LR method) was used to study the association between eGFR and hypoglycaemia incidence. RESULTS: Included were 39 316 patients (mean age 68.0 ± 18.0 years, 49.3% males, 25.9% with DM, eGFR 69.5 ± 24.9 mL/min/1.73 m2 ). Among study participants, 6.5% had at least one hypoglycaemic event. Logistic regression modelling showed that eGFR was inversely associated with incident hypoglycaemia (OR 0.988, 95% CI 0.986-0.990, p < .001). Results were similar for patients with and without DM. Estimated GFR was negatively correlated with admission CRP levels for patients with (r = -.143, p < .001) and without DM (r = -.166, p < .001). Estimated GFR was also positively correlated with admission serum albumin levels for both patients with (r = .304, p < .001) and without DM (r = .354, p < .001). CONCLUSION: Among non-critically-ill patients hospitalized in internal medicine departments, reduced eGFR is associated with increased risk of hypoglycaemia. Glucose monitoring for all inpatients with CKD is suggested, regardless of DM status.

Occlusive Mesenteric Ischemia in Chronic Dialysis Patients.

BACKGROUND: Among dialysis patients, occlusive mesenteric vascular disease has rarely been reported. OBJECTIVES: To report on the experience of one center with regard to diagnosing and treating this complication. METHODS: The retrospective case-series involved six patients (3 females, 3 males; age 52-88 years; 5/6 were smokers) on chronic hemodialysis at a single center. All patients with symptoms suggestive of occlusive mesenteric disease and a subsequent angiographic intervention were included. Demographic, clinical, and laboratory data were collected from patient charts for the period before and after angioplasty and stenting of the mesenteric vessels. A Wilcoxon signed-rank test was used to compare the relevant data before and after the intervention. RESULTS: All participants had variable co-morbidities and postprandial abdominal pain, food aversion, and weight loss. CT angiography was limited due to heavy vascular calcifications. All underwent angioplasty with stenting of the superior mesenteric artery (4 patients) or the celiac artery (2 patients). All procedures were successful in resolving abdominal pain, malnutrition, and inflammation. Weight loss before was 15 ± 2 kg and weight gain after was 6 ± 2 kg. C-reactive protein decreased from 13.4 ± 5.2 mg/dl to 2.2 ± 0.4 mg/dl (P < 0.05). Serum albumin increased from 3.0 ± 0.2 g/dl to 3.9 ± 0.1 g/dl (P < 0.05). Two patients underwent a repeat procedure (4 years, 5 months, respectively). Follow-up ranged from 0.5-7 years. CONCLUSIONS: Occlusive mesenteric ischemia occurs among dialysis patients. The diagnosis requires a high degree of suspicion, and it is manageable by angiography and stenting of the most involved mesenteric artery.

Remote Health Monitoring During and After the COVID-19 Pandemic.

High importance of the remote health monitoring (RHM) especially during and after the pandemic is accentuated in this article. It is displayed that by this way it is possible to revealing automatically situations "suspicious" from the COVID-19 illness view point for some concrete patients and also to keep up with possible complications after the illness. Another great opportunity of the RHM is connected with investigation of the vaccines. RHM allows reveal cases of the complications among the patients as well as positive and negative consequences of the vaccination. The general depersonalized data should be gathered and analyzed to research the regularities of the COVID-19 sickness rate and the complications frequency and also of the safety and effectiveness of the vaccines. It is proposed to combine advantages of RHM for medical care for concrete patients with opened opportunities for research to reveal important general normality connected with correlation between COVID-19 complications and peculiarities of various chronic diseases and specific medical statements. Telemedicine platform intended for creation of RHM systems is described. It has gone through the pilot running in Russian medical institutions and now presented good results have been achieved.

Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study.

OBJECTIVES: We aimed to evaluate the rates of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity. METHODS: This was a prospective cohort study including consecutive kidney transplant recipients in a single referral transplant centre. Participants were tested for anti-spike (anti-S) antibodies 2-4 weeks after a second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity. RESULTS: Of 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2-4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titre was 15.5 AU/mL (interquartile range (IQR) 3.5-163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio (OR) 1.025 per mL/min/1.73 m2, 95% confidence interval (CI) 1.014-1.037, p < 0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95%CI 1.782-3.089, p < 0.001), younger age (OR 1.032 per year decrease, 95%CI 1.015-1.05, p < 0.001) and lower calcineurin inhibitor (CNI) blood level (OR 1.987, 95%CI 1.146-3.443, p 0.014). No serious adverse events resulting from the vaccine were reported. CONCLUSIONS: Kidney transplant recipients demonstrated an inadequate antibody response to SARS-CoV-2 mRNA vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies.

Microalbuminuria After Kidney Transplantation Predicts Cardiovascular Morbidity.

Background: Microalbuminuria is a well-characterized marker of kidney malfunction, both in diabetic and non-diabetic populations, and is used as a prognostic marker for cardiovascular morbidity and mortality. A few studies implied that it has the same value in kidney transplanted patients, but the information relies on spot or dipstick urine protein evaluations, rather than the gold standard of timed urine collection. Methods: We revisited a cohort of 286 kidney transplanted patients, several years after completing a meticulously timed urine collection and assessed the prevalence of major cardiovascular adverse events (MACE) in relation to albuminuria. Results: During a median follow up of 8.3 years (IQR 6.4-9.1) 144 outcome events occurred in 101 patients. By Kaplan-Meier analysis microalbuminuria was associated with increased rate of CV outcome or death (p = 0.03), and this was still significant after stratification according to propensity score quartiles (p = 0.048). Time dependent Cox proportional hazard analysis showed independent association between microalbuminuria and CV outcomes 2 years following microalbuminuria detection (HR 1.83, 95% CI 1.07-2.96). Conclusions: Two years after documenting microalbuminuria in kidney transplanted patients, their CVD risk was increased. There is need for primary prevention strategies in this population and future studies should address the topic.

Association of obesity and muscle mass with risk of albuminuria in renal transplant recipients.

BACKGROUND: Increased albuminuria is a predictor of graft loss in kidney graft recipients. It is unknown whether obesity is an independent risk factor for the development of increased albuminuria in this population. The aim of this study was to elucidate the association between obesity and albuminuria in renal transplant recipients. METHODS: We enrolled 330 renal transplant recipients and prospectively collected demographic, anthropomorphic, clinical and laboratory variables susceptible to influence albumin excretion. The outcome was albuminuria, measured using accurately timed urine collections. Data from 201 patients were analyzed after exclusion of participants with missing data and patients enrolled less than 6 months since renal transplantation. Analysis was carried out for an early and a late period, defined according to the 2.4-year median follow-up time. RESULTS: Body mass index (BMI), waist circumference and urinary creatinine excretion rate were independent predictors of albuminuria in the late post-transplant period, indicating that the predictive value of body mass index for albuminuria is related to both increased abdominal fat mass and increased muscle mass. BMI was an independent predictor of microalbuminuria. Waist circumference and urinary creatinine were independent predictors of microalbuminuria for values above certain cutoffs: 110% of the accepted thresholds defining abdominal obesity and 1500 mg/day, respectively. CONCLUSIONS: These associations, which have not previously been reported, suggest, but do not prove, that an imbalance between metabolic demand and nephron mass may be responsible for increased albuminuria in the renal transplant population.

Cessation of Bezafibrate in patients with chronic kidney disease improves renal function.

Bezafibrate (BzF) is eliminated by renal excretion and dosage must be reduced in patients with chronic kidney disease (CKD). There is a concern that BzF causes a further deterioration in renal function in patients with CKD. This study assessed whether BzF discontinuation or dose reduction in CKD patients improves renal function. 117 CKD patients treated with BzF between 2009 and 2014 were studied for demographics, comorbid conditions and laboratory variables. Data compared 2 groups: an intervention group of 64 patients where recommendations regarding BzF administration was implemented and a control group of 37 patients. Follow-up was maintained for 12 months. In the intervention group, estimated glomerular filtration rate (eGFR) increased from 38 to 42 mL/min/1.73 m2 (p = 0.01); blood urea levels decreased from 81 to 77 mg/dL (p = 0.04). Serum creatinine decreased by more than 0.2 mg/dL in 45% of the intervention group, as compared to 19% of the control group (p < 0.01). Improvement in eGFR was seen exclusively in patients who stopped BzF completely (eGFR increased from 38 to 44 mL/min/1.73 m2). In the intervention group, TG level increased from 183 to 220 mg/dL (p < 0.001). BzF cessation in approximately 50% of patients with CKD was associated with an increase in eGFR.

Blockchain as a Process Control Tool for Healthcare.

The blockchain is one of the most popular information technologies and, at the same time, it was discredited by stories about crashes of multiple cryptocurrency projects. Even though this technology has recently found application in many areas not related to cryptocurrencies, mainly for security purposes, the attitude towards it remains wary. Herein we shall try to demonstrate that blockchain is something going far beyond cryptocurrency and security issues, and may become one of the fundamental information technologies in future healthcare.