Association of kidney function with physical performance: the Maastricht study.

BACKGROUND: Kidney failure has been associated with decreased physical capacity, although evidence regarding the physical performance of individuals with earlier stages of chronic kidney disease (CKD) remains limited. METHODS: Cross-sectional data were derived from the prospective, population-based Maastricht Study. Multivariate linear regression models were fitted to assess the association of estimated glomerular filtration rate (eGFR) and albuminuria categories with physical performance test outcomes. RESULTS: Overall, 7396 participants were included. Compared to eGFR 60-90 ml/min/1.73 m2, values < 60 ml/min/1.73 m2 were associated with significantly shorter 6-min walk distance (ß: - 13.04 m, 95% confidence intervals-CI - 19.95; - 6.13), worse timed chair rise stand test time (ß: 0.91 s, 95% CI 0.36; 1.47), lower maximal grip (ß: - 0.83 kg, 95% CI - 1.50; - 0.15) and elbow flexion (ß: - 3.64 Nm, 95% CI - 7.11; - 0.16) strength. Additionally, eGFR > 90 ml/min/1.73 m2 was linked to significantly shorter 6-min walk distance (ß: - 6.13 m, 95% CI - 9.44; - 2.82). Urinary albumin excretion > 30 mg/24 h was associated with shorter 6-min walk distance (ß: - 12.48 m, 95% CI - 18.28; - 6.68), worse timed chair rise stand test time (ß: 0.51 s, 95% CI 0.11; 1.06), lower maximal grip (ß: - 1.34 kg, 95% CI - 1.91; - 0.76) and elbow flexion strength (ß: - 3.31 Nm, 95% CI - 5.80; - 0.82). CONCLUSIONS: Reduced eGFR and higher albuminuria levels were associated with worse physical performance, especially shorter 6-min walk distance and lower muscle strength. The relationship between eGFR and physical function was non-linear, with also high eGFR values being associated with worse performance, especially in the six-minute walk test.

Sociodemographic Disparities in Adults with Kidney Failure: A Meta-Analysis.

This meta-analysis aims to assess current evidence regarding sociodemographic disparities among adults with kidney failure. Medline, Scopus, Web of Science, CENTRAL, and Google Scholar were systematically searched from inception to 20 February 2022. Overall, 165 cohort studies were included. Compared to White patients, dialysis survival was significantly better among Black (hazard ratio-HR: 0.68; 95% CI: 0.61-0.75), Asian (HR: 0.67; 95% CI: 0.61-0.72) and Hispanic patients (HR: 0.80; 95% CI: 0.73-0.88). Black individuals were associated with lower rates of successful arteriovenous fistula use, peritoneal dialysis and kidney transplantation, as well as with worse graft survival. Overall survival was significantly better in females after kidney transplantation compared to males (HR: 0.87; 95% CI: 0.84-0.90). Female sex was linked to higher rates of central venous catheter use and a lower probability of kidney transplantation. Indices of low SES were associated with higher mortality risk (HR: 1.22, 95% CI: 1.14-1.31), reduced rates of dialysis with an arteriovenous fistula, peritoneal dialysis and kidney transplantation, as well as higher graft failure risk. In conclusion, Black, Asian and Hispanic patients present better survival in dialysis, while Black, female and socially deprived patients demonstrate lower rates of successful arteriovenous fistula use and limited access to kidney transplantation. PROSPERO registration: CRD42022300839.

Association of physical activity with endothelial dysfunction among adults with and without chronic kidney disease: The Maastricht Study.

BACKGROUND AND AIMS: Physical activity (PA) constitutes an established protective factor while sedentary behavior (SB) an emerging independent risk factor for cardiovascular diseases. This study evaluated the association of PA and SB with endothelial dysfunction (ED) depending on kidney function status. METHODS: Cross-sectional data from the prospective, population-based Maastricht Study were used. PA and SB were measured using the ActivPAL3 accelerometer 24h/day for eight consecutive days. ED was evaluated by plasma levels of soluble vascular cell adhesion protein-1, intercellular adhesion molecule-1, E-selectin and von Willebrand factor, which were combined into an ED score with higher values depicting higher ED. RESULTS: Overall, 2,668 participants, 323 with chronic kidney disease, were included. In normal kidney function individuals, the ED score presented a significant negative association with total, lower-intensity and moderate-to-vigorous PA duration and a positive association with total sedentary time, sedentary breaks and sedentary bout duration. In participants with chronic kidney disease, a significant negative association of ED score with total [ß: -4.42, 95% confidence intervals (95% CI): -7.98; -0.87] and lower-intensity (ß: -7.08, 95% CI: -13.41; -0.74) PA duration, as well as a positive association of ED score with sedentary bout duration (ß: 43.72, 95% CI: 9.85; 77.59) were noted. The strength of associations did not significantly differ across kidney function subgroups (p > 0.05). CONCLUSIONS: This analysis showed that PA duration is inversely associated with ED both among patients with normal kidney function and chronic kidney disease. In chronic kidney disease, longer sedentary bouts were associated with greater endothelial dysfunction.

Assessment of mRNA Vaccine Immunogenicity in Solid Organ Transplant Recipients.

Background and Objectives: Solid organ transplant (SOT) recipients have a higher risk of suffering from severe Coronavirus (COVID-19) compared to the general population. Studies have shown impaired immunogenicity of mRNA vaccines in this high-risk population; thus, SOT recipients have been prioritized globally for primary and booster doses. Materials and Methods: We analyzed 144 SOT recipients who had previously received two doses of BNT162b2 or mRNA1273 vaccine, and who were subsequently vaccinated with a booster dose of the mRNA1273 vaccine. Humoral and cellular immune responses were measured 1 and 3 months after the second dose, and 1 month after the third dose. Results: One month after the second dose, 33.6% (45/134) of patients displayed a positive antibody response with a median (25th, 75th) antibody titer of 9 (7, 161) AU/mL. Three months after the second dose, 41.8% (56/134) tested positive with a median (25th, 75th) antibody titer of 18 (7, 251) AU/mL. After the booster dose, the seropositivity rate increased to 69.4% (93/134), with a median (25th, 75th) titer of 966 (10, 8027) AU/mL. The specific SARS-CoV-2 T-cell response was assessed in 44 randomly selected recipients 3 months after the second dose, and 11.4% (5/44) of them had a positive response. Following the third dose, 42% (21/50) tested positive. Side effects after the third dose were mild, with pain at the injection site being the most frequent adverse effect, reported by 73.4% of the recipients. Conclusion: Our study shows a mild delayed increase in antibody titer, three months after primary vaccination compared to one month after. It also shows a robust augmentation of humoral and specific T-cell responses after the booster dose, as well as the safety and tolerability of the mRNA vaccines in SOT recipients.

Impaired cerebral autoregulation in Fabry disease: A case-control study.

BACKGROUND AND PURPOSE: Cerebral small vessel disease is a common manifestation among patients with Fabry disease (FD). As a biomarker of cerebral small vessel disease, the prevalence of impaired cerebral autoregulation as assessed by transcranial Doppler (TCD) ultrasonography was evaluated in FD patients and healthy controls. METHODS: TCD was performed to assess pulsatility index (PI) and vasomotor reactivity expressed by breath-holding index (BHI) for the middle cerebral arteries of included FD patients and healthy controls. Prevalence of increased PI (>1.2) and decreased BHI (<0.69) and ultrasound indices of cerebral autoregulation were compared in FD patients and controls. The potential association of ultrasound indices of impaired cerebral autoregulation with white matter lesions and leukoencephalopathy on brain MRI in FD patients was also evaluated. RESULTS: Demographics and vascular risk factors were similar in 23 FD patients (43% women, mean age: 51 ± 13 years) and 46 healthy controls (43% women, mean age: 51 ± 13 years). The prevalence of increased PI (39%; 95% confidence interval [CI]: 20%-61%), decreased BHI (39%; 95% CI: 20%-61%), and the combination of increased PI and/or decreased BHI (61%; 95% CI: 39%-80%) was significantly (p < .001) higher in FD patients compared to healthy controls (2% [95% CI: 0.1%-12%], 2% [95% CI: 0.1%-12%], and 4% [95% CI: 0.1%-15%], respectively). However, indices of abnormal cerebral autoregulation were not associated independently with white matter hyperintensities and presented a low-to-moderate predictive ability for the discrimination of FD patients with and without white matter hyperintensities. CONCLUSIONS: Impaired cerebral autoregulation as assessed by TCD appears to be highly more prevalent among FD patients compared to healthy controls.

The Influence of Antibodies against Angiotensin II Type-1 Receptor on the Outcome of Kidney Transplantation: A Single-Center Retrospective Study.

Allo- and autoimmune mechanisms are involved in kidney allograft rejection and loss. This study investigates the impact of anti-angiotensin II type-1 receptor antibodies (anti-AT1RAbs) detected alone or in association with HLA donor-specific antibodies (HLA-DSAs) on the outcome of kidney transplantation (KTx). Anti-AT1RAbs and HLA-DSAs were detected in 71 kidney transplant (KT) recipients who developed biopsy-proven acute or chronic active T-cell rejection (TCMR) (n = 51) or antibody-mediated rejection (ABMR) (n = 20), forming the rejection group (RG). The control group (CG) included 71 KTx recipients with comparable characteristics without rejection. All patients had been transplanted with negative T/B flow crossmatch (T/BFCXM). The median follow-up period was 3.7 years. Antibodies were determined pre- and periodically post-KTx by Luminex method for HLA-DSAs and enzyme-linked immunosorbent assay for anti-AT1RAbs. Before KTx, twenty-three (32.4%) patients in the RG, sixteen with TCMR and seven with ABMR, were found anti-AT1Rabs-positive (≥10 U/mL) versus eleven (15.5%) patients in the CG (p = 0.031). Simultaneous detection of preformed anti-AT1RAbs and HLA-DSAs was found in five patients of the RG versus two of the CG (p = 0.355). At the time of transplant biopsy, fifteen (21.1%) patients, four with ABMR and eleven with TCMR, were positive for anti-AT1RAbs. Anti-AT1RAbs and HLA-DSAs were detected simultaneously in 7/15 (46.7%) cases, three with ABMR and four with TCMR. During the follow-up, thirteen (18.3%) patients in the RG, eight with ABMR and five with TCMR, lost their graft compared to one patient (1.4%) in the CG (p = 0.001). Six out of thirteen (46.2%) RG patients who lost the graft were found positive for anti-AT1RAbs pretransplant. Patient survival with functioning graft did not differ significantly between anti-AT1Rabs-positive and negative KT recipients (log-rank p = 0.88). Simultaneous detection of anti-ATR1Abs and HLA-DSAs did not have a significant influence on patient survival with functioning graft (log-rank p = 0.96). Graft function at the end of the follow-up was better, but not significantly, in anti-AT1Rabs-negative patients, with serum creatinine 1.48 [1.20-1.98] mg/dL and eGFR (CKD-EPI) 48.5 [33.5-59.0] mL/min/1.73 m2, compared to anti-AT1Rabs-positive ones who had serum creatinine 1.65 [1.24-2.02] mg/dL (p = 0.394) and eGFR (CKD-EPI) 47.0 [34.8-60.3] mL/min/1.73 m2 (p = 0.966). Anti-AT1RAbs detection pretransplant characterizes KT recipients at increased risk of cellular or antibody-mediated rejection. Furthermore, anti-AT1RAbs, detected alone or simultaneously with HLA-DSAs, appear to be associated with impaired graft function, but their role in graft survival has not been documented in this study. Screening for these antibodies appears to complement pretransplant immunological risk assessment.

Τhe Impact of Pre-Transplant Kidney Biopsy on the Evaluation of Prospective Living Kidney Donors.

Living kidney donation contributes to increasing the donor pool. Since safety and excellent outcomes of living kidney donors (LKD) are essential, renal biopsy must be part of the pre-transplant evaluation in donors with isolated urine abnormalities or other risk factors. We retrospectively collected data on potential living donors evaluated in the pre-transplant outpatient clinic of Laiko General Hospital of Athens between 2007 and 2022, who underwent a pre-transplant biopsy. Biopsy indications included microscopic hematuria, borderline proteinuria and comorbidities suggestive of chronicity. Those with glomerular diseases or chronic lesions were excluded from donation. We identified 59 potential living donors who underwent renal biopsy. Of these, 10 (16.9%) were male. Median age was 58 (IQR 51-63) years, while 23 (39%) were older than 60 years. 49 out of 59 (83%) had glomerular hematuria, 10 (16.7%) had proteinuria (150-300 mg/d). Out of the 59 donors, 21 (35.6%) were hypertensive, three (5.1%) had impaired glucose tolerance and seven (11.9%) had a BMI > 30 kg/m2. A total of 32 (54.2%) potential donors were accepted for donation. Eight (13.6%) had IgA nephropathy, 10 (16.9%) TBMD and nine (15.3%) had increased chronicity including secondary FSGS. When compared with a control group of donors who did not need a pre-transplant biopsy, those 32 who donated were more frequently hypertensive (p = 0.003), but had similar eGFR [61.3 (±10.4) vs. 61.9 (±13.8), p = 0.866] after a follow-up of 79 (36-114) months. Renal biopsy is a useful tool in the evaluation of prospective LKD. Thorough assessment of donors with isolated urine abnormalities and marginal donors is critical to ensure good post-donation outcomes.

Disease Course, Management and Outcomes in Kidney Transplant Recipients with SARS-CoV-2 Infection during the Omicron-Variant Wave: A Single-Center Experience.

BACKGROUND: Since December 2019, kidney transplant recipients (KTRs) have experienced a great impact of the coronavirus disease 2019 (COVID-19) pandemic, with a higher risk of morbidity and mortality compared to the general population. Preliminary data in KTRs suggest that the Omicron variant, which has been dominant since December 2021, is more infectious than the previous ones but is associated with reduced risk of severity and low lethality rates. The purpose of our study was to assess the disease course and outcomes of the SARS-CoV-2 infection in KTRs during the Omicron-surge. METHODS: This retrospective study included 451 KTRs diagnosed with SARS-CoV-2 infection between 1 December 2021 and 30 September 2022. Demographic and clinical characteristics at the time of infection, vaccination data, treatment, clinical course, and outcomes were recorded and analyzed. RESULTS: Mean age was 51.8 ± 13.7 years with a male predominance (61.2%). The majority (76.1%) were vaccinated with at least three doses of the available mRNA vaccines, although serology revealed low anti-SARS-CoV-2 antibody titers before infection (33 [3.3-1205] AU/mL). Only 6% of the patients experienced moderate-severe disease. Accordingly, there was low prevalence of adverse outcomes, such as SARS-CoV-2-related hospitalization (11.3%) and death (0.9%). Multivariate analysis revealed that only age significantly increased the risk of SARS-CoV-2-related hospitalization. CONCLUSIONS: During the Omicron wave, the clinical course of the SARS-CoV-2 infection in KTRs has substantially changed, with lower rates of moderate and severe disease and a low prevalence of adverse outcomes. Prospective clinical trials are warranted to further elucidate the evolving pathogenesis, management, and long-term outcomes of COVID-19 in such high-risk populations.

Evaluation of Kidney Donor Risk Index/Kidney Donor Profile Index as Predictor Tools of Deceased-Donor Kidney Transplant Outcomes in a Greek Cohort.

The Kidney Donor Risk Index (KDRI) and Kidney Donor Profile Index (KDPI) have been developed to assess deceased-donor graft quality, although validation of their utility outside the USA remains limited. This single-center retrospective cohort study evaluated the ability of KDRI and KDPI to predict transplant outcomes in a Greek cohort. The efficacy of KDRI, KDPI, and donor's age in predicting death-censored graft failure was primarily assessed. Overall, 394 donors and 456 recipients were included. Death-censored graft survival was significantly worse with increasing KDRI (hazard ratio-HR: 2.21, 95% confidence intervals-CI: 1.16-4.22), KDPI (HR: 1.01, 95% CI: 1.00-1.02), and donor's age (HR: 1.03, 95% CI: 1.00-1.05). The unadjusted discriminative ability was similar for KDPI (C-statistic: 0.54) and donor's age (C-statistic: 0.52). The KDPI threshold of 85 was not predictive of graft failure (p-value: 0.19). Higher KDPI was linked to delayed graft function and worse kidney function, but not among expanded-criteria donor transplantations. No significant association was found between KDRI, KDPI, and patient survival. In conclusion, increasing KDRI and KDPI are linked to worse graft function, although their ability to discriminate long-term graft failure remains limited.

Kidney transplantation and kidney donation do not affect short-term blood pressure variability.

PURPOSE: Blood pressure variability (BPV) is an independent cardiovascular risk factor in CKD. Kidney transplantation (KTx) is associated with improved BP levels for kidney transplant recipient (KTRs), without evoking significant changes in donors. The aim of this study was to assess the short- and mid-time effects of KTx and donation on short-term BPV in KTRs and their respective living kidney donors. MATERIALS AND METHODS: Forty KTRs and their respective donors were evaluated with 24-h ABPM (Mobil-O-Graph-NG) at baseline (1 month before), 3-months and 12-months after KTx. Standard-deviation (SD), weighted-SD (wSD), coefficient-of-variation (CV), average-real-variability (ARV) and variability independent of mean (VIM) for SBP/DBP were calculated with validated formulas. RESULTS: All 24-h systolic and diastolic BPV indexes studied did not change significantly from baseline to 3-month (SBP-wSD: 12.8 ± 3.0 vs 13.2 ± 3.4 mmHg, p = 0.608; SBP-ARV: 10.3 ± 2.4 vs 10.8 ± 2.6 mmHg, p = 0.463) and 12-month evaluation (SBP-wSD 12.8 ± 3.0 vs 12.1 ± 2.8; p = 0.424 and SBP-ARV: 10.3 ± 2.4 vs 10.2 ± 2.5; p = 0.615) after kidney transplantation in the KTRs.In kidney donors, all 24-h systolic BPV indices displayed a trend towards higher values at 3 months compared to baseline, but without reaching statistical significance (SBP-wSD: 12.2 ± 2.8 vs 13.6 ± 4.2 mmHg, p = 0.107 and SBP-ARV: 10.1 ± 2.1 vs 11.2 ± 3.1 mmHg, p = 0.099), the levels of 24-h systolic SBP indices at 12-months were almost identical to baseline values. 24-h diastolic BPV indices at 3-month and 12-month evaluation were similar to baseline. CONCLUSION: Short-term BPV did not change significantly 3 and 12 months after kidney transplantation/donation neither in KTRs nor in living kidney donors. Longitudinal studies examining associations of BPV with adverse outcomes in these individuals are needed.

What is the context? Previous studies have shown that both office and ambulatory BP levels are significantly reduced after kidney transplantation in KTRs.On the other hand, existing evidence suggests that kidney donors' BP levels do not change significantly after kidney donation.Existing studies on BPV in KTRs are limited. The available data for living kidney donors are even fewer.What is new? This is the first study assessing short-term BPV levels in ΚTRs undergoing living donor kidney transplantation, and their respective donors in short-term and mid-term follow-up. The main findings were:All 24-h, daytime and night-time BPV indexes did not change significantly from baseline to 3- and 12-month evaluation after kidney transplantation in the KTRs.No significant changes for the 24-h, daytime and night-time BPV were observed in their respective kidney donors at the same follow-up periods.What is the impact?High BPV, which seems to remain unaltered after kidney transplantation, may be one of the many factors involved in the high cardiovascular risk observed in KTRs.Unchanged BPV levels further supports the evidence suggesting no higher risks of arrhythmias, cardiovascular events or death after living kidney donation.

Immunogenicity of the Two mRNA SARS-CoV-2 Vaccines in a Large Cohort of Dialysis Patients.

Chronic kidney disease patients, especially those on hemodialysis, are at the highest risk of a severe course and death from COVID-19. Moreover, they appear to have suboptimal response in both cellular and humoral immunity after vaccination. The present study investigated humoral and cellular response and safety after two doses of either of the two authorized mRNA vaccines in a cohort of 310 patients on maintenance dialysis. The antibody response rate was 94.5%, with a median (25th, 75th) antibody titer of 3478 (1236, 8141) AU/mL. Only mild adverse effects were observed. Only vaccine type was independently associated with immunogenicity. Α statistically significant difference in favor of mRNA1273 versus BNT162b2 vaccine was observed. Antibody positivity (100% vs. 94.3%, p < 0.001), median (25th, 75th) antibody levels: 9499 (6118, 20,780) AU/mL vs. 3269 (1220, 7807) AU/mL (p < 0.001). Among the 65 patients tested for T-cell response, 27 (41.5%) had a positive one with a median (25th, 75th) antibody titer of 6007 (3405, 12,068) AU/mL, while 38 with no T-cell response presented a lower median (25th, 75th) antibody titer of 1744 (850, 4176) AU/mL (p < 0.001). Both mRNA vaccines are safe for dialysis patients and can trigger humoral and cellular responses, although with lower titers than those that have been reported to healthy individuals.

D313Y Variant in Fabry Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: There is accumulating evidence in the literature indicating a strong correlation between Fabry disease (FD) phenotypes and specific sequence variations in the Galactosidase Alpha (GLA) gene. Among them, the potential pathogenicity and clinical relevance of D313Y variation in patients with FD remain debated. METHODS: We performed a systematic review and meta-analysis of studies reporting D313Y as single occurring variant in the GLA gene and sought to evaluate (1) the prevalence of D313Y variation in different populations with or without clinical manifestations of FD, (2) the clinical FD phenotype in D313Y-positive patients, and (3) the proportion of D313Y-positive patients presenting abnormal laboratory findings (alpha-galactosidase-A deficiency or globotriaosylceramide accumulation). RESULTS: Forty cohorts comprising 211 individuals with D313Y variation among 42,723 participants with available GLA gene-sequencing data were included. Patients highly suspected for FD had a higher prevalence of D313Y variation (4.9%, 95% CI 1.6%-9.9%; I2 = 95.5%) compared with the general population (0%, 95% CI 0%-0.1%; I2 = 1.9%; p = 0.004). The prevalence of D313Y variation was 0.6% (95% CI 0.3%-1%; I2 = 74.1%), 0.4% (95% CI 0.2%-0.7%; I2 = 0%), and 0.3% (95% CI 0.2%-0.4%; I2 = 0%) in patients presenting with neurologic, cardiac, or renal manifestations, respectively. D313Y was associated with a milder, late-onset FD phenotype, as indicated by the mean patient age of 51 years (95% CI 44-59; I2 = 94%) and the evidence of alpha-galactosidase A deficiency and globotriaosylceramide accumulation in 26.7% (95% CI 15.3%-40%; I2 = 34%) and 16.2% (95% CI 8%-26.4%; I2 = 35%) of cases, respectively. D313Y-positive patients displayed predominantly neurologic FD manifestations (58.1%, 95% CI 37.7%-77.1%; I2 = 78%), with central and peripheral nervous system (CNS/PNS) involvement noted in 28.2% (95% CI 15.4%-43.2%; I2 = 51%) and 28.5% (95% CI 17.8%-40.5%; I2 = 61%) of cases, respectively. DISCUSSION: D313Y variation seems to correlate with an atypical, mild late-onset phenotype with predominantly neurologic FD manifestations. Monitoring for CNS/PNS involvement is thus paramount to identify D313Y-positive patients with latent or early-FD pathology, which may qualify for enzyme-replacement therapy or chaperone treatment.

Sex-related short-term blood pressure variability differences in kidney transplant recipients.

OBJECTIVE: Kidney transplant recipients (KTRs) display higher cardiovascular morbidity and mortality than the general population. Increased short-term blood pressure variability (BPV) is associated with a higher risk of adverse cardiovascular outcomes in chronic kidney disease (CKD). The aim of this study is to investigate sex differences in short-term BPV in KTRs. METHODS: In total, 136 male and 69 female KTRs with valid 24 h ambulatory blood pressure monitoring were included in this analysis. Systolic and diastolic BPV indices [SD, weighted SD (wSD), coefficient of variation (CV), average real variability (ARV) and variability independent of the mean (VIM)] were calculated with validated formulas for the 24 h, daytime and nighttime periods. RESULTS: Age, time from transplantation surgery and history of major comorbidities did not differ between men and women. During the 24-h period, systolic BPV indices did not differ between men and women (SBP-ARV: 9.4 ± 2.2 vs. 9.9 ± 2.5; P = 0.212). During the daytime period, SBP-CV and SBP-VIM were significantly higher in females compared with male participants (SBP-CV: 9.9 ± 2.4 vs. 11 ± 3.1%; P = 0.022 and SBP-VIM: 12.6 ± 3.0 vs 14.2 ± 3.9; P = 0.008); daytime SBP-SD and SBP-ARV, and all studied indexes during nighttime did not differ between groups. No significant between-group differences in 24 h and daytime diastolic BPV indices were detected. Nighttime DBP-CV was marginally higher in men (12.0 ± 3.6 vs. 11.4 ± 4.0; P = 0.053); the rest nighttime diastolic BPV indices measured were also nonsignificantly higher in men. CONCLUSION: In conclusion, 24-h systolic and diastolic BPV parameters did not differ between male and female KTRs, but short-term BPV over the respective day- and nighttime periods showed different trends in men and women. Further studies are needed to examine possible differences in long-term BPV in KTRs.

Ambulatory blood pressure trajectories and blood pressure variability in kidney transplant recipients: a comparative study against chronic kidney disease patients.

BACKGROUND: Hypertension is a major cardiovascular risk factor in both kidney transplant recipients (KTRs) and patients with chronic kidney disease (CKD). Ambulatory blood pressure monitoring (ABPM) is considered the gold-standard method for hypertension management in these subjects. This is the first study evaluating the full ambulatory blood pressure (BP) profile and short-term BP variability (BPV) in KTRs versus CKD patients without kidney replacement therapy. METHODS: Ninety-three KTRs were matched with 93 CKD patients for age, sex, and estimated glomerular filtration rate. All participants underwent 24-hour ABPM. Mean ambulatory BP levels, BP trajectories, and BPV indices (standard deviation [SD], weighted SD, and average real variability) were compared between the two groups. RESULTS: There were no significant between-group differences in 24-hour systolic BP (SBP)/diastolic BP (DBP) (KTRs: 126.9 ± 13.1/79.1 ± 7.9 mmHg vs. CKD: 128.1 ± 11.2/77.9 ± 8.1 mmHg, p = 0.52/0.29), daytime SBP/DBP and nighttime SBP; nighttime DBP was slightly higher in KTRs (KTRs: 76.5 ± 8.8 mmHg vs. CKD: 73.8 ± 8.8 mmHg, p = 0.04). Repeated measurements analysis of variance showed a significant effect of time on both ambulatory SBP and DBP (SBP: F = [19, 3002] = 11.735, p < 0.001, partial η2 = 0.069) but not of KTR/CKD status (SBP: F = [1, 158] = 0.668, p = 0.42, partial η2 = 0.004). Ambulatory systolic/diastolic BPV indices were not different between KTRs and CKD patients, except for 24-hour DBP SD that was slightly higher in the latter group (KTRs: 10.2 ± 2.2 mmHg vs. CKD: 10.9 ± 2.6 mmHg, p = 0.04). No differences were noted in dipping pattern between the two groups. CONCLUSION: Mean ambulatory BP levels, BP trajectories, and short-term BPV indices are not significantly different between KTRs and CKD patients, suggesting that KTRs have a similar ambulatory BP profile compared to CKD patients without kidney replacement therapy.

Ambulatory blood pressure trajectories and blood pressure variability in kidney transplant recipients: a comparative study against haemodialysis patients.

Background: Hypertension is the most prevalent cardiovascular risk factor in kidney transplant recipients (KTRs). Preliminary data suggest similar ambulatory blood pressure (BP) levels in KTRs and haemodialysis (HD) patients. This is the first study comparing the full ambulatory BP profile and short-term BP variability (BPV) in KTRs versus HD patients. Methods: A total of 204 KTRs were matched (2:1 ratio) with 102 HD patients for age and gender. BP levels, BP trajectories and BPV indices over a 24-h ambulatory BP monitoring (ABPM) in KTRs were compared against both the first and second 24-h periods of a standard 48-h ABPM in HD patients. To evaluate the effect of renal replacement treatment and time on ambulatory BP levels, a two-way ANOVA for repeated measurements was performed. Results: KTRs had significantly lower systolic blood pressure (SBP) and pulse-pressure (PP) levels compared with HD patients during all periods studied (24-h SBP: KTR: 126.5 ± 12.1 mmHg; HD first 24 h: 132.0 ± 18.1 mmHg; P = 0.006; second 24 h: 134.3 ± 17.7 mmHg; P < 0.001); no significant differences were noted for diastolic blood pressure levels with the exception of the second nighttime. Repeated measurements ANOVA showed a significant effect of renal replacement therapy modality and time on ambulatory SBP levels during all periods studied, and a significant interaction between them; the greatest between-group difference in BP (KTRs-HD in mmHg) was observed at the end of the second 24 h [-13.9 mmHg (95% confidence interval -21.5 to -6.2); P < 0.001]. Ambulatory systolic and diastolic BPV indices were significantly lower in KTRs than in HD patients during all periods studied (24-h SBP average real variability: KTRs: 9.6 ± 2.3 mmHg; HD first 24 h: 10.3 ± 3.0 mmHg; P = 0.032; second 24 h: 11.5 ± 3.0 mmHg; P < 0.001). No differences were noted in dipping pattern between the two groups. Conclusions: SBP and PP levels and trajectories, and BPV were significantly lower in KTRs compared with age- and gender-matched HD patients during all periods studied. These findings suggest a more favourable ambulatory BP profile in KTRs, in contrast to previous observations.

Head-to-Head Comparison of Response Rates to the Two mRNA SARS-CοV-2 Vaccines in a Large Cohort of Solid Organ Transplant (SOT) Recipients.

Due to their higher risk of developing life-threatening COVID-19 disease, solid organ transplant (SOT) recipients have been prioritized in the vaccination programs of many countries. However, there is increasing evidence of reduced immunogenicity to SARS-CοV-2 vaccination. The present study investigated humoral response, safety, and effectiveness after the two mRNA vaccines in 455 SOT recipients. Overall, the antibody response rate was low, at 39.6%. Higher immunogenicity was detected among individuals vaccinated with the mRNA1273 compared to those with the BNT162b2 vaccine (47% vs. 36%, respectively, p = 0.025) as well as higher median antibody levels of 31 (7, 372) (AU/mL) vs. 11 (7, 215) AU/mL, respectively. Among the covariates assessed, vaccination with the BNT162b2 vaccine, antimetabolite- and steroid-containing immunosuppression, female gender, the type of transplanted organ and older age were factors that negatively influenced immune response. Only mild adverse effects were observed. Our findings confirm poor immunogenicity after vaccination, implicating a reevaluation of vaccination policy in SOT recipients.

Prevalence and factors associated with hyperkalaemia in stable kidney transplant recipients.

BACKGROUND: Hyperkalaemia is a frequent and potentially life-threatening condition in patients with chronic kidney disease (CKD). Even after successful kidney transplantation (KTx), KTx recipients have mild to severe CKD. Moreover, they share comorbid conditions and frequently use medications that predispose to hyperkalaemia. This study aimed to examine the prevalence and factors associated with hyperkalaemia in this population. METHODS: Over a pre-specified period of 6 months (1 September 2019 to 31 March 2020), we recorded in cross-sectional fashion information on serum potassium (K+) and relevant demographics, comorbidities, medications, laboratory and transplant-associated variables in clinically stable KTx recipients attending the Transplant Outpatient Clinic of our Department. Ηyperkalaemia was classified as follows: serum K+ level >5.0 mEq/L; and further as >5.0 mEq/L with concomitant use of sodium (Na+) polystyrene sulphonate; serum K+ ≥5.2 mEq/L; serum K+ ≥5.5 mEq/L. Univariate and multiple logistic regression analyses were used to identify factors associated with serum K+ >5.0 mEq/L. RESULTS: The study population consisted of 582 stable KTx recipients, 369 (63.4%) males, aged 52.4 ± 13.5 years, with estimated glomerular filtration rate (eGFR) of 55.8 ± 20.1 mL/min/1.73 m2 transplanted for >1 year. The prevalence of hyperkalaemia defined as K+ >5.0 mEq/L; >5.0 mEq/L and use of Na+ polystyrene sulphonate; K+ ≥5.2; or K+ ≥5.5 mEq/L, was: 22.7, 22.7, 14.4 and 4.1% (132, 132, 84 and 24 patients), respectively. In multivariate analysis, male gender [odds ratio (OR) = 2.020, 95% confidence interval (CI) 1.264-3.227] and use of renin-angiotensin-aldosterone system (RAAS) blockers (OR = 1.628, 95% CI 1.045-2.536) were independently associated with hyperkalaemia, while higher eGFR (OR = 0.967, 95% CI 0.955-0.979) and use of non-K+-sparing diuretics (OR = 0.140, 95% CI 0.046-0.430) were associated with lower odds of the disorder. CONCLUSIONS: The prevalence of mild hyperkalaemia in stable KTx recipients is relatively high but that of moderate or severe hyperkalaemia is low. Among a wide range of factors studied, only male gender and RAAS blockade were associated with increased odds of hyperkalaemia, while higher eGFR and diuretics were associated with decreased odds of hyperkalaemia.

Assessment of hypertension in kidney transplantation by ambulatory blood pressure monitoring: a systematic review and meta-analysis.

BACKGROUND: Hypertension (HTN) is common following renal transplantation and it is associated with adverse effects on cardiovascular (CV) and graft health. Ambulatory blood pressure monitoring (ABPM) is the preferred method to characterize blood pressure (BP) status, since HTN misclassification by office BP (OBP) is quite common in this population. We performed a systematic review and meta-analysis aimed at determining the clinical utility of 24-h ABPM and its potential implications for the management of HTN in this population. METHODS: Ovid-MEDLINE and PubMed databases were searched for interventional or observational studies enrolling adult kidney transplant recipients (KTRs) undergoing 24-h ABP readings compared with OBP or home BP. The main outcome was the proportion of KTRs diagnosed with HTN by ABPM, home or OBP recordings. Additionally, day-night BP variability and dipper/non-dipper status were assessed. RESULTS: Forty-two eligible studies (4115 participants) were reviewed. A cumulative analysis including 27 studies (3481 participants) revealed a prevalence of uncontrolled HTN detected by ABPM of 56% [95% confidence interval (CI) 46-65%]. The pooled prevalence of uncontrolled HTN according to OBP was 47% (95% CI 36-58%) in 25 studies (3261 participants). Very few studies reported on home BP recordings. The average concordance rate between OBP and ABPM measurements in classifying patients as controlled or uncontrolled hypertensive was 66% (95% CI 59-73%). ABPM revealed HTN phenotypes among KTRs. Two pooled analyses of 11 and 10 studies, respectively, revealed an average prevalence of 26% (95% CI 19-33%) for masked HTN (MHT) and 10% (95% CI 6-17%) for white-coat HTN (WCH). The proportion of non-dippers was variable across the 28 studies that analysed dipping status, with an average prevalence of 54% (95% CI 45-63%). CONCLUSIONS: In our systematic review, comparison of OBP versus ABP measurements disclosed a high proportion of MHT, uncontrolled HTN and, to a lesser extent, WCH in KTRs. These results suggest that HTN is not adequately diagnosed and controlled by OBP recordings in this population. Furthermore, the high prevalence of non-dippers confirmed that circadian rhythm is commonly disturbed in KTRs.

Occurrence of Severe SARS-CoV-2 Infection in Fully Vaccinated Solid Organ Transplant Recipients.

The present study presents the clinical outcome of SARS-CoV-2 disease in relation to the humoral response in fully vaccinated solid organ transplant (SOT) recipients. Our patient cohort consists of 455 SOT recipients, vaccinated with one of the 2 approved mRNA vaccines. The antibody response was measured 1 month after the second dose, and previously infected patients have been excluded. Of the 449 remaining patients, 15 (3.34%) tested positive, using SARS-CoV-2 polymerase chain reaction. Their mean age was 43.7 ±14.4 years, and median time from transplantation was 7.8 years (1.2-30.2). Eleven patients (73.3%) had been vaccinated with BNT162b2 and 4 (26.7%) with the mRNA1273 vaccine. At the time of infection 9 (60%) patients had a negative (<50 AU/mL) antibody titer, and 6 (40%) had a positive one (>50 AU/mL). Median antibody titer, 27.4± 14.0 days after the second dose, measured at 13 AU/mL (0-7480 AU/mL). Renal function did not appear to be affected by the disease. Τhe mean estimated glomerular filtration rate at diagnosis was 48 ± 15 mL/min, and when in a 29-day (1-101) median follow-up was 53.9± 20.9 mL/min. Of the 15 patients, 7 had mild symptoms and were not hospitalized, and of the remaining 8 (53.3%) who needed hospitalization 7 had severe disease and 2 of them expired. The study confirms the variable and often severe course of coronavirus 2019 infection in SOT recipients, even after their full vaccination, highlighting the need to vaccinate their close relatives and to accelerate the implementation of the booster dose of vaccine.

Sex differences in ambulatory blood pressure levels, control, and phenotypes of hypertension in kidney transplant recipients.

OBJECTIVES: Ambulatory blood pressure (BP) control is worse in men compared with women with chronic kidney disease (CKD) and this may partially explain the faster CKD progression in men. This is the first study investigating possible sex differences in prevalence, control and phenotypes of hypertension in kidney transplant recipients (KTRs) with office-BP and 24-h ambulatory BP monitoring (ABPM). METHODS: This cross-sectional study included 136 male and 69 female stable KTRs who underwent office-BP measurements and 24-h ABPM. Hypertension thresholds for office and ambulatory BP were defined according to the 2017 ACC/AHA and 2021 KDIGO guidelines for KTRs. RESULTS: Age, time from transplantation, eGFR and history of major comorbidities did not differ between groups. Office SBP/DBP levels were insignificantly higher in men than women (130.3 ±â€Š16.3/77.3 ±â€Š9.4 vs. 126.4 ±â€Š17.8/74.9 ±â€Š11.5 mmHg; P = 0.118/0.104) but daytime SBP/DBP was significantly higher in men (128.5 ±â€Š12.1/83.0 ±â€Š8.2 vs. 124.6 ±â€Š11.9/80.3 ±â€Š9.3 mmHg; P = 0.032/P = 0.044). No significant between-group differences were detected for night-time BP. The prevalence of hypertension was similar by office-BP criteria (93.4 vs. 91.3%; P = 0.589), but higher in men than women with ABPM (100 vs. 95.7%; P = 0.014). The use of ACEIs/ARBs and CCBs was more common in men. Office-BP control was similar (43.3 vs. 44.4%, P = 0.882), but 24-h control was significantly lower in men than women (16.9 vs. 30.3%; P = 0.029). White-coat hypertension was similar (5.1 vs. 7.6%; P = 0.493), whereas masked hypertension was insignificantly more prevalent in men than women (35.3 vs. 24.2%; P = 0.113). CONCLUSION: BP levels, hypertension prevalence and control are similar by office criteria but significantly different by ABPM criteria between male and female KTRs. Worse ambulatory BP control in male compared with female KTRs may interfere with renal and cardiovascular outcomes.