Sodium-glucose co-transporter 2 inhibitors for all-cause and cardiovascular death in people with different stages of CKD: A systematic review and meta-analysis.

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors (SGLT2is) reduce cardiovascular risk in people with diabetes and established cardiovascular disease, but emerging studies in chronic kidney disease (CKD) have inconsistent results. In this systematic review, we evaluate the effects of SGLT2is on cardiovascular mortality in people with CKD as a whole and across subgroups stratified by baseline kidney function and among people at low, moderate, high and very high risk according to KDIGO- CKD classification system. METHODS: Literature search was conducted in PubMed/MEDLINE, Cochrane/CENTRAL, Scopus and Web of Science up to 30 November 2023. We included randomized controlled trials assessing the effect of SGLT2is on cardiovascular mortality in people with CKD. Secondary outcomes included all-cause mortality and major adverse cardiac events (MACE). RESULTS: Eleven studies (n = 83,203 participants) were included. In people with CKD, treatment with SGLT2is compared to placebo reduced the risk of cardiovascular death by 14% (hazard ratio [HR] .86; 95%CI .79-.94), all-cause death by 15% (HR .85; 95%CI .79-.91) and MACEs by 13% (HR .87; 95%CI .81-.93). A consistent treatment effect was observed across eGFR-subgroups (≥60 mL/min/1.73 m2: HR .82, 95%CI .65-1.02; <60 mL/min/1.73 m2: HR .86, 95%CI .77-.96, p-subgroup difference = .68) and KDIGO risk-categories (low, moderate, high and very high) (p-subgroup difference = .69) for cardiovascular death; reduction in the risk of all-cause death tended to be greater in the highest KDIGO risk categories. A consistent treatment effect on cardiovascular mortality was observed for different SGLT2is agents studied. Sensitivity analysis for cardiovascular mortality endpoint including studies in diabetic people yielded similar results (HR .86; 95%CI .77-.97). CONCLUSIONS: Treatment with SGLT2is led to a significant reduction in the risk of cardiovascular and all-cause mortality in people with different CKD stages. These findings support the use of SGLT2is as an adjunct cardiovascular protective therapy in CKD. PROSPERO REGISTRATION NUMBER: PROSPERO registration number: CRD42022382863.

A commentary from the European Renal Best Practice (ERBP) on the Kidney Disease Improving Global Outcomes (KDIGO) 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease in children and adults.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Guidelines for identification and management of chronic kidney disease (CKD) are a welcome development coming 12 years after the paradigm changing 2012 guidelines. We are living in an unprecedented era in nephrology with novel therapies, including sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists now being proven in multiple randomised controlled clinical trials to reduce both the progression of CKD and cardiovascular morbidity and mortality. The KDIGO 2024 CKD guideline is aimed at a broad audience looking after children and adults with CKD and provide practical and actionable steps to improve care. This commentary reviews the guideline sections pertaining to the evaluation and risk assessment of individuals with CKD from a European perspective. We feel that despite the last guideline being published 12 years ago, and that the assessment of CKD has been emphasized by many other national/international nephrology, cardiology and diabetology guidelines and societies, the diagnosis and treatment of CKD remains poor across Europe. As such the KDIGO 2024 CKD Guidelines should be seen as an urgent call to action to improve diagnosis and care of children and adults with CKD across Europe. We know what we need to do. We now need to get on and do it.

Low dialysate sodium and 48-h ambulatory blood pressure in patients with intradialytic hypertension: a randomized crossover study.

BACKGROUND: Intradialytic hypertension (IDH) is associated with increased risk for cardiovascular events and mortality. Patients with IDH exhibit higher 48-h blood pressure (BP) levels than patients without this condition. Volume and sodium excess are considered a major factor contributing in the development of this phenomenon. This study evaluated the effect of low (137 mEq/L) compared with standard (140 mEq/L) dialysate sodium concentration on 48-h BP in patients with IDH. METHODS: In this randomized, single-blind, crossover study, 29 patients with IDH underwent four hemodialysis sessions with low (137 mEq/L) followed by four sessions with standard (140 mEq/L) dialysate sodium, or vice versa. Mean 48-h BP, pre-/post-dialysis and intradialytic BP, pre-dialysis weight, interdialytic weight gain (IDWG) and lung ultrasound B-lines were assessed. RESULTS: Mean 48-h systolic/diastolic BP (SBP/DBP) were significantly lower with low compared with standard dialysate sodium concentration (137.6 ± 17.0/81.4 ± 13.7 mmHg with low vs 142.9 ± 14.5/84.0 ± 13.9 mmHg with standard dialysate sodium, P = .005/P = .007, respectively); SBP/DBP levels were also significantly lower during the 44-h and different 24-h periods. Low dialysate sodium significantly reduced post-dialysis (SBP/DBP: 150.3 ± 22.3/91.2 ± 15.1 mmHg with low vs 166.6 ± 17.3/94.5 ± 14.9 mmHg with standard dialysate sodium, P < .001/P = .134, respectively) and intradialytic (141.4 ± 18.0/85.0 ± 13.4 mmHg with low vs 147.5 ± 13.6/88.1 ± 12.5 mmHg with standard dialysate sodium, P = .034/P = .013, respectively) BP compared with standard dialysate sodium. Pre-dialysis weight, IDWG and pre-dialysis B lines were also significantly decreased with low dialysate sodium. CONCLUSIONS: Low dialysate sodium concentration significantly reduced 48-h ambulatory BP compared with standard dialysate sodium in patients with IDH. These findings support low dialysate sodium as a major non-pharmacologic approach for BP management in patients with IDH. TRIAL REGISTRATION: ClinicalTrials.gov study number NCT05430438.

Efficacy of pharmacologic interventions on magnetic resonance imaging biomarkers in patients with nonalcoholic fatty liver disease: systematic review and network meta-analysis.

BACKGROUND AND AIM: Several agents are under investigation for nonalcoholic fatty liver disease (NAFLD). We assessed the comparative efficacy of pharmacologic interventions for patients with NAFLD focusing on magnetic resonance imaging (MRI) biomarkers. METHODS: We searched Medline, Embase, and CENTRAL. We included randomized controlled trials of more than 12 weeks of intervention that recruited patients with biopsy-confirmed or MRI-confirmed NAFLD and assessed the efficacy of interventions on liver fat content (LFC) and fibrosis by means of MRI. We performed random-effects frequentist network meta-analyses and assessed confidence in our estimates using the CINeMA (Confidence in Network Meta-Analysis) approach. RESULTS: We included 47 trials (8583 patients). Versus placebo, thiazolidinediones were the most efficacious for the absolute change in LFC, followed by vitamin E, fibroblast growth factor (FGF) analogs, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with mean differences ranging from -7.46% (95% confidence interval [-11.0, -3.9]) to -4.36% (-7.2, -1.5). No differences between drug classes were evident. Patients receiving GLP-1 RAs or glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs were more likely to achieve ≥30% relative reduction in LFC. Among agents, efruxifermin produced the largest reduction in LFC compared to placebo [-13.5% (-18.5, -8.5)], followed by pioglitazone, while being superior to most interventions. The effect of interventions on magnetic resonance elastography assessed fibrosis was small and insignificant. The confidence in our estimates was low to very low. CONCLUSIONS: Several drug classes may reduce LFC in patients with NAFLD without a significant effect on fibrosis; nevertheless, trial duration was small, and confidence in the effect estimates was low.

Cardiorespiratory fitness assessed with cardiopulmonary exercise testing in patients with juvenile idiopathic arthritis: a systematic review and meta-analysis.

OBJECTIVES: JIA is the most common type of arthritis in children and adolescents, causing joint damage, chronic pain and disability. Deconditioning is also prevalent in patients with JIA due to both inactivity and the disease progression, resulting in reduced cardiorespiratory fitness (CRF). We aimed to evaluate CRF of patients with JIA compared with healthy controls. METHODS: This is a systematic review and meta-analysis of studies using cardiopulmonary exercise testing (CPET) to examine differences in determinants of CRF between patients with JIA vs healthy controls. The primary outcome was peak oxygen uptake (VO2peak). Literature search involved PubMed, Web of Science and Scopus databases, manual search of article references and grey literature. Quality assessment was undertaken with Newcastle-Ottawa Scale. RESULTS: From 480 literature records initially retrieved, eight studies (538 participants) were included in final meta-analysis. VO2peak was significantly lower in patients with JIA compared with controls [weighted mean difference (WMD): -5.95 ml/kg/min (95% CI -9.26, -2.65)]. Exercise duration and VO2peak (% predicted) were found to be significantly impaired in patients with JIA compared with controls [standardized mean difference: -0.67 (95% CI -1.04, -0.29) and WMD: -11.31% (95% CI -20.09, -2.53), respectively], while no significant differences were found in maximum heart rate. CONCLUSION: VO2peak and other CPET variables were lower in patients with JIA compared with controls, indicating reduced CRF in the former. Overall, exercise programs for patients with JIA should be promoted as part of their treatment to improve physical fitness and reduce muscle atrophy. PROSPERO REGISTRATION: CRD42022380833.

Association of Intradialytic Hypertension with Future Cardiovascular Events and Mortality in Hemodialysis Patients: Effects of Ambulatory Blood Pressure.

INTRODUCTION: Intradialytic hypertension (IDHTN) is associated with increased risk of adverse outcomes. Patients with IDHTN have higher 44-h blood pressure (BP) than patients without this condition. Whether the excess risk in these patients is due to the BP rise during dialysis per se or on elevated 44-h BP or other comorbid conditions is uncertain. This study evaluated the association of IDHTN with cardiovascular events and mortality and the influence of ambulatory BP and other cardiovascular risk factors on these associations. METHODS: 242 hemodialysis patients with valid 48-h ABPM (Mobil-O-Graph-NG) were followed for a median of 45.7 months. IDHTN was defined as: systolic BP (SBP) rise ≥10 mm Hg from pre- to post-dialysis and post-dialysis SBP ≥150 mm Hg. The primary endpoint was all-cause mortality; the secondary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, heart failure hospitalization, coronary or peripheral revascularization. RESULTS: Cumulative freedom from both the primary and secondary endpoint was significantly lower for IDHTN patients (logrank-p = 0.048 and 0.022, respectively), corresponding to higher risks for all-cause mortality (hazard ratio (HR) = 1.566; 95% confidence interval (CI) [1.001, 2.450]) and the composite cardiovascular outcome (HR = 1.675; 95% CI [1.071, 2.620]) in these individuals. However, the observed associations lost statistical significance after adjustment for 44-h SBP (HR = 1.529; 95% CI [0.952, 2.457] and HR = 1.388; 95% CI [0.866, 2.225], respectively). In the final model after additional adjustment for 44-h SBP, interdialytic weight gain, age, history of coronary artery disease, heart failure, diabetes, and 44-h pulse wave velocity, the association of IDHTN with the outcomes was also not significant and the respective HRs were 1.377 (95% CI [0.836, 2.268]) and 1.451 (95% CI [0.891, 2.364]). CONCLUSIONS: IDHTN patients had higher risk for mortality and cardiovascular outcomes but this risk is at least partly confounded by the elevated BP levels during the interdialytic period.

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.

Ambulatory central BP and arterial stiffness in patients with and without intradialytic hypertension.

BACKGROUND: Increased arterial stiffness is suggested to be involved in the pathogenesis of intradialytic-hypertension (IDH). Ambulatory pulse-wave-velocity (PWV) is an independent predictor for all-cause-mortality in haemodialysis and its prognostic power is better than office PWV. This is the first study examining ambulatory central blood pressure (BP) and arterial stiffness parameters in patients with and without IDH. METHODS: This study examined 45 patients with IDH (SBP rise ≥10 mmHg from pre- to post-dialysis and post-dialysis SBP ≥150 mmHg) in comparison with 197 patients without IDH. All participants underwent 48-h ABPM with Mobil-O-Graph-NG; parameters of central haemodynamics, wave reflection and PWV were estimated. RESULTS: Age, dialysis vintage and interdialytic weight gain did not differ between-groups. IDH patients had higher 48-h cSBP (131.7 ± 16.2 vs. 119.2 ± 15.2 mmHg, p < 0.001), 48-h cDBP (86.7 ± 12.7 vs. 79.6 ± 11.5 mmHg, p < 0.001) and 48-h cPP (45.5 ± 10.4 vs. 39.8 ± 10.0 mmHg, p = 0.001) compared to patients without IDH. Similarly, during day- and nighttime periods, cSBP/cDBP and cPP levels were higher in IDH-patients compared to non-IDH. Forty-eight-hour augmentation pressure and index, but not AIx(75) were higher in IDH patients; 48-h PWV (10.0 ± 2.0 vs. 9.2 ± 2.1 m/s, p = 0.017) was significantly higher in patients with IDH. The two study groups displayed different trajectories in central BP and PWV over the course of the recording; IDH patients had steadily high values of the above variables during the 2 days of the interdialytic-interval, whereas non-IDH patients showed a gradual elevation, with significant increases from the 1st to 2nd 24 h. CONCLUSIONS: IDH patients have significantly higher levels of ambulatory central BP and arterial stiffness parameters and a different course over the 48-h period compared with non-IDH patients. Increased arterial stiffness could be a prominent factor associated with the high burden of cardiovascular disease in this population.

Accuracy of Peridialytic, Intradialytic, and Scheduled Interdialytic Recordings in Detecting Elevated Ambulatory Blood Pressure in Hemodialysis Patients.

RATIONALE & OBJECTIVE: Current recommendations suggest the use of ambulatory blood pressure monitoring (ABPM) as the gold standard for hypertension diagnosis and management in hemodialysis patients. This study assesses the accuracy of peridialytic, intradialytic, and scheduled interdialytic recordings in detecting abnormally elevated 44-hour interdialytic blood pressure (BP). STUDY DESIGN: Diagnostic test study. SETTINGS & PARTICIPANTS: 242 Greek hemodialysis patients who successfully underwent ABPM. TESTS COMPARED: Ambulatory BP was used as the reference method to evaluate the accuracy of the following BP metrics: predialysis and postdialysis BP, intradialytic BP, intradialytic plus pre/postdialysis BP, and scheduled interdialytic BP (on an off-dialysis day at 8:00 am, 8:00 pm, and their average). OUTCOME: 44-hour ambulatory systolic BP/diastolic BP (SBP/DBP) ≥ 130/80 mm Hg. RESULTS: The 44-hour SBP/DBP levels differed significantly from predialysis and postdialysis BP but showed no or minor differences compared with the other BP metrics. Bland-Altman plots showed an absence of systematic bias for all metrics but large between-method difference and wider 95% limits of agreement for predialysis and postdialysis BP compared with intradialytic, intradialytic plus pre/postdialysis, and averaged scheduled interdialytic BP. The sensitivity/specificity and κ-statistic for diagnosing 44-hour SBP ≥ 130 mm Hg were low for predialysis (86.5%/38.6%, κ-statistic = 0.27) and postdialysis BP (63.1%/73.3%, κ-statistic = 0.35), but better for intradialytic BP (77.3%/76.2%, κ-statistic = 0.53), intradialytic plus pre/postdialysis BP (76.6%/72.3%, κ-statistic = 0.49), and scheduled interdialytic BP (87.9%/77.2%, κ-statistic = 0.66). In receiver operating characteristic (ROC) analyses, the areas under the curve (AUC) of predialysis SBP (AUC = 0.723) and postdialysis SBP (AUC = 0.746) were significantly lower than that of intradialytic SBP (AUC = 0.850), intradialytic plus pre/postdialysis SBP (AUC = 0.850), and scheduled interdialytic SBP (AUC = 0.917) (z test, P < 0.001 for all pairwise comparisons). Similar observations were made for DBP. LIMITATIONS: Typical home BP data were not obtained, and no assessment was obtained of the reproducibility of the examined metrics over time. CONCLUSIONS: Intradialytic, intradialytic plus pre/postdialysis, and scheduled interdialytic BP measurements were more accurate in detecting elevated 44-hour BP than predialysis and postdialysis BP. Averaged intradialytic BP recordings or scheduled readings at the off-dialysis day appear to be promising approaches to the diagnosis of elevated BP in hemodialysis.

The effect of different dialysate sodium concentrations on ambulatory blood pressure in hemodialysis patients: a prospective interventional study.

Background: Hypertension is associated with increased morbidity and mortality in hemodialysis patients. Existing recommendations suggest reduction of sodium load, but the effect of dialysate sodium on blood pressure (BP) is not fully elucidated. The aim of the present study is to investigate the effect of different dialysate sodium concentrations on 72-h ambulatory BP in hemodialysis patients. Methods: This prospective study included patients on standard thrice-weekly hemodialysis. All patients initially underwent six sessions with dialysate sodium concentration of 137 meq/L, followed consecutively by another six sessions with dialysate sodium of 139 meq/L and, finally, six sessions with dialysate sodium of 141 meq/L. At the start of the sixth hemodialysis session on each sodium concentration, 72-h ABPM was performed over the long interdialytic interval to evaluate ambulatory systolic and diastolic BP (SBP and DBP) during the overall 72-h, different 24-h, daytime and night-time periods. Results: Twenty-five patients were included in the final analysis. A significant increase in the mean 72-h SBP was observed with higher dialysate sodium concentrations (124.8 ± 16.6 mmHg with 137 meq/L vs 126.3 ± 17.5 mmHg with 139 meq/L vs 132.3 ± 19.31 mmHg with 141 meq/L, P = 0.002). Similar differences were noted for DBP; 72-h DBP was significantly higher with increasing dialysate sodium concentrations (75.1 ± 11.3 mmHg with 137 meq/L vs 76.3 ± 13.7 mmHg with 139 meq/L vs 79.5 ± 13.9 mmHg with 141 meq/L dialysate sodium, P = 0.01). Ambulatory BP during the different 24-h intervals, daytime and night-time periods was also progressively increasing with increasing dialysate sodium concentration. Conclusion: This pilot study showed a progressive increase in ambulatory BP with higher dialysate sodium concentrations. These findings support that lower dialysate sodium concentration may help towards better BP control in hemodialysis patients.

Accuracy of 24 h ambulatory blood pressure recordings for diagnosing high 44 h blood pressure in hemodialysis: a diagnostic test study.

Hypertension is highly prevalent in hemodialysis patients. Ambulatory-BP-monitoring(ABPM) during the 44 h interdialytic interval is recommended for hypertension diagnosis and management in these subjects. This study assessed the diagnostic accuracy of fixed 24 h ABPM recordings with 44 h BP in hemodialysis patients. 242 Greek hemodialysis patients that underwent valid 48 h ABPM(Mobil-O-Graph NG device) were included in the analysis. We used 44 h BP as reference method and tested the accuracy of the following BP metrics: 1st 24 h without HD period (20 h-1st), 1st 24 h including HD period (24 h-1st) and 2nd 24 h(24 h-2nd). All studied metrics showed strong correlations with 44 h SBP/DBP (20 h-1st: r = 0.973/0.978, 24 h-1st: r = 0.964/0.972 and 24 h-2nd: r = 0.978/0.977, respectively). In Bland-Altman analysis, small between-method differences (-1.70, -1.19 and +1.45 mmHg) with good 95% limits-of agreement([-10.83 to 7.43], [-11.12 to 8.74] and [-6.33 to 9.23] mmHg, respectively) for 20 h-1st, 24 h-1st and 24 h-2nd SBP were observed. The sensitivity/specificity and κ-statistic for diagnosing 44 h SBP ≥ 130 mmHg were high for 20 h-1st SBP(87.2%/96.0%, κ-statistic = 0.817), 24 h-1st SBP(88.7%/96.0%, κ-statistic = 0.833) and 24 h-2nd SBP (95.0%/88.1%, κ-statistic = 0.837). Similar observations were made for DBP. In ROC-analyses, all studied BP metrics showed excellent performance with high Area-Under-the- Curve values (20 h-1st: 0.983/0.992; 24 h-1st: 0.984/0.987 and 24 h-2nd: 0.982/0.989 for SBP/DBP respectively). Fixed 24 h ABPM recordings during either the first or the second day of interdialytic interval have high accuracy and strong agreement with 44 h BP in hemodialysis patients. Thus, ABPM recordings of either the first or the second interdialytic day could be used for hypertension diagnosis and management in these subjects.

The association of sex differences in ambulatory blood pressure with cardiovascular events and mortality in dialysis patients.

Male patients with pre-dialysis chronic kidney disease (CKD) have worse ambulatory blood pressure (BP) control than females; this is associated with higher mortality. Male hemodialysis patients have higher ambulatory BP levels than females. This analysis aimed to investigate the association of sex differences in ambulatory BP with cardiovascular events and mortality in hemodialysis individuals. 129 male and 91 female hemodialysis patients with valid 48-h BP monitoring were followed for 53.4 ± 31.1 months. The primary endpoint was cardiovascular mortality; the secondary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, resuscitation after cardiac arrest, heart failure-hospitalization, coronary or peripheral revascularization. Cumulative freedom from the primary endpoint was lower for women (logrank-p = 0.032), while cumulative-freedom from the secondary endpoint did not differ significantly between-groups (logrank-p = 0.644). The crude risk for cardiovascular mortality was significantly higher in women (HR = 1.613, 95% CI [1.037, 2.509]). The crude risk for the combined endpoint was not different between the two groups (HR = 0.918, 95% CI [0.638, 1.320]). After adjusting for major risk factors (age, diabetes, dialysis vintage, coronary disease and hemoglobin) no significant differences in the risk for both the primary and the secondary endpoint were observed between women and men (primary: HR = 1.295 (95% CI [0.808, 2.078]), secondary: HR = 0.763 (95% CI [0.521, 1.118])). After additional adjustment for 44-h systolic BP the above relationships did not alter (primary: HR = 1.329 (95% CI [0.826, 2.137]), secondary: HR = 0.808 (95% CI [0.551, 1.184])). In conclusion, female hemodialysis patients have higher crude but similar adjusted cardiovascular mortality rates compared to male counterparts. In contrast to pre-dialysis CKD, the neutral relationship between gender and adverse cardiovascular outcomes in hemodialysis is not further affected by ambulatory BP.

Dialysate sodium and short-term blood pressure variability in patients with intradialytic hypertension: a randomized crossover study.

Increased blood pressure (BP) variability (BPV) is associated with high cardiovascular risk in hemodialysis. Patients with intradialytic hypertension (IDH) also exhibit an increased cardiovascular risk compared to hemodialysis patients without this condition. The impact of non-pharmacological BP-lowering interventions on BPV in this population remains unknown. This analysis evaluated the effect of low (137mEq/L) compared to standard (140mEq/L) dialysate sodium concentration on short-term BPV in patients with IDH. In a randomized cross-over manner, 29 IDH patients underwent 4 hemodialysis sessions with low (137mEq/L) followed by 4 sessions with standard (140mEq/L) dialysate sodium or vice versa. 48 h ambulatory BP measurement was performed from the start of the 4th session on each dialysate sodium. BPV indices during the 48 h, 24 h, day-time and night-time periods were calculated. Mean 48 h BP was 5.3/2.6 mmHg lower with low compared to standard dialysate sodium concentration, (p = 0.005/p = 0.007 respectively). All 48 h systolic BPV indices examined showed non-significant differences between low and standard dialysate sodium (SBP-SD: 16.99 ± 5.39 vs. 16.98 ± 4.33 mmHg, p = 0.982; SBP-wSD: 15.93 ± 5.02 vs. 16.12 ± 4.16 mmHg, p = 0.769; SBP-ARV: 11.99 ± 3.67 vs. 11.45 ± 3.35 mmHg, p = 0.392; SBP-CV: 12.36 ± 3.65 vs. 11.92 ± 3.18%, p = 0.302, with low vs. standard dialysate sodium, respectively). Diastolic BPV indices were numerically, but not statistically, lower with low dialysate sodium. Overall, significant differences were observed in some comparisons with a trend for lower BPV during day-time 2 and higher BVP during night-time 2 with low dialysate sodium. In conclusion, low dialysate sodium concentration does not affect BPV levels in patients with IDH. Future research should explore alternative interventions to reduce BP and BPV in this high-risk population.

Effect of heart failure and atrial fibrillation on cardiorespiratory fitness in hemodialysis patients.

PURPOSE: Heart failure (HF) and atrial fibrillation (AF) are highly prevalent in hemodialysis. They are well-known significant modifiers of the disease associations with cardiovascular outcomes, but there is a lack of evidence regarding the effects of HF and AF on cardiorespiratory fitness. This study is the first to examine the possible association of the presence of HF and AF with exercise intolerance in patients undergoing hemodialysis. METHODS: This analysis included 40 sex- and age-matched participants [10 hemodialysis patients with HF or AF, 10 hemodialysis patients without HF or AF, 10 patients with HF or AF without chronic kidney disease (CKD) and 10 healthy controls] that underwent CPET and spirometry examinations. The total of patients with HF had preserved ejection fraction. RESULTS: VO2peak(ml/kg/min) showed a graded increase between hemodialysis patients with HF or AF, hemodialysis patients without HF or AF, non-CKD patients with HF or AF and controls (13.17 ± 2.45 vs 15.26 ± 3.29 vs 19.64 ± 5.84 vs 25.11 ± 6.94 ml/kg/min, p < 0.001); VO2peak(ml/min) followed the same pattern (1172 ± 197 vs 1269 ± 314 vs 1817 ± 583 vs 1952 ± 592 ml/min respectively, p = 0.001). VO2peak(%predicted), VO2AT(ml/kg/min), VO2AT(ml/min) and maximal work load significantly differed between the study groups, with a tendency for higher values from hemodialysis patients to non-CKD patients with HF or AF and to healthy controls. FEV1 and FVC levels were similar between the study groups. In the whole population, VO2peak(ml/kg/min) showed a positive correlation with hemoglobin (r = 0.663, p < 0.001) and negative correlations with high-sensitivity cardiac troponin I (r = - 0.493, p = 0.001) and BNP (r = - 0.479, p = 0.002). CONCLUSION: Hemodialysis patients have low exercise tolerance, and the presence of HF or AF is associated with further decreased values of VO2peak, the most important determinant of cardiorespiratory fitness.

Direct Oral Anticoagulants Versus Vitamin K Antagonists for the Management of Left Ventricular Thrombus After Myocardial Infarction: A Meta-Analysis.

Left ventricular (LV) thrombus formation remains a post-acute myocardial infarction (AMI) complication even in the modern era of early reperfusion. The optimal anticoagulation regimen in this clinical scenario is poorly defined. The present meta-analysis sought to investigate the efficacy and safety profile of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for the management of LV thrombus after AMI. A systematic literature review was conducted in electronic databases to identify studies reporting efficacy and safety outcome data regarding the use of DOACs versus VKAs for patients with LV thrombus after AMI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and random-effects meta-analyses were conducted to synthesize pooled ORs. Eight studies comprising a total of 605 patients were included. DOACs were associated with an almost twofold higher likelihood of thrombus resolution compared with VKAs (pooled OR 1.95 [1.25 to 3.04], p = 0.003, I2 = 0%), and decreased the risk of systemic embolism by 70% (pooled OR 0.30 [0.12 to 0.75]; p = 0.01, I2 = 0%). The use of DOACs was associated with a 54% lower risk of bleeding compared with VKAs (pooled OR 0.46 [0.26 to 0.84], p = 0.01, I2 = 0%). Overall, patients receiving DOACs had a 63% lower risk of reaching the composite outcome of safety and efficacy compared with patients using VKAs (pooled OR 0.37 [0.23 to 0.60], p <0.0001, I2 = 0%). In conclusion, DOACs appear to have a more favorable efficacy and safety profile compared with VKAs for the management of LV thrombus related to AMI.

Measures of wave intensity as a non-invasive surrogate for cardiac function predicts mortality in haemodialysis patients.

Background: Risk prediction in haemodialysis (HD) patients is challenging due to the impact of the dialysis regime on the patient's volume status and the complex interplay with cardiac function, comorbidities and hypertension. Cardiac function as a key predictor of cardiovascular (CV) mortality in HD patients is challenging to assess in daily routine. Thus the aim of this study was to investigate the association of a novel, non-invasive relative index of systolic function with mortality and to assess its interplay with volume removal. Methods: A total of 558 (373 male/185 female) HD patients with a median age of 66 years were included in this analysis. They underwent 24-hour ambulatory blood pressure monitoring, including wave intensity analysis [i.e. S:D ratio (SDR)]. All-cause and CV mortality served as endpoints and multivariate proportional hazards models were used for risk prediction. Intradialytic changes were analysed in tertiles according to ultrafiltration volume. During a follow-up of 37.8 months, 193 patients died (92 due to CV reasons). Results: The SDR was significantly associated with all-cause {univariate hazard ratio [HR] 1.36 [95% confidence interval (CI) 1.20-1.54], P < .001} and CV [univariate HR 1.41 (95% CI 1.20-1.67), P < .001] mortality. The associations remained significant in multivariate analysis accounting for possible confounders. Changes in the SDR from pre-/early- to post-dialytic averages were significantly different for the three ultrafiltration volume groups. Conclusion: This study provides well-powered evidence for the independent association of a novel index of systolic function with mortality. Furthermore, it revealed a significant association between intradialytic changes of the measure and intradialytic volume removal.

Right Ventricular and Right Atrial Strain Are Associated with Kidney Dysfunction in Acute Heart Failure.

BACKGROUND: In acute heart failure (HF), low cardiac output and venous congestion are pathophysiological mechanisms that contribute to renal function impairment. This study investigated the association between advanced echocardiographic measures of right ventricular and atrial function and renal impairment in patients with acute HF. METHODS AND RESULTS: A total of 377 patients hospitalized for acute HF were prospectively evaluated. Estimated glomerular filtration rate (eGFR) on admission was measured using the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine equation. Advanced echocardiographic assessment was performed on admission. Patients with eGFR < 45 mL/min/1.73 m2 were more likely to have chronic heart failure, chronic atrial fibrillation, and type 2 diabetes mellitus compared to patients with eGFR ≥ 45 mL/min/1.73 m2. Patients with lower eGFR had lower cardiac output, higher mean E/e' ratio, larger right ventricular (RV) size, worse RV free wall longitudinal strain, more impaired right atrial (RA) reservoir strain, and more frequent severe tricuspid regurgitation. RV free wall longitudinal strain and RA reservoir strain were the only independent echocardiographic associates of low eGFR, whereas cardiac output was not. CONCLUSIONS: Impaired RV and RA longitudinal strain were independently associated with eGFR < 45 mL/min/1.73 m2 in acute HF, while reduced cardiac output was not. This suggests that RV and RA dysfunction underlying venous congestion and increased renal afterload are more important pathophysiological determinants of renal impairment in acute HF than reduced cardiac output.

Hyperkalemia in chronic kidney disease: a focus on potassium lowering pharmacotherapy.

INTRODUCTION: Hyperkalemia is one of the most common electrolyte disorders in chronic kidney disease (CKD) and is associated with serious adverse outcomes. Hyperkalemia risk is even greater when CKD patients also have additional predisposing conditions such as diabetes or heart failure. Renin-angiotensin-aldosterone-system blockers are first-line treatments for cardio- and nephroprotection, but their use is often limited due to K+ elevation, resulting in high rates of discontinuation. AREAS COVERED: This article provides an overview of factors interfering with K+ homeostasis and discusses recent data on newer therapeutic agents used for the treatment of hyperkalemia. A detailed literature search was performed in two major databases (PubMed/MEDLINE and Scopus) up to April 2023. EXPERT OPINION: Major clinical trials have tested new and promising kidney protective therapies such as sodium/glucose-cotransporter-2 inhibitors and mineralocorticoid-receptor-antagonists, with promising results. Until recently, the only treatment option for hyperkalemia was the cation-exchanging resin sodium-polystyrene-sulfonate. However, despite its common use, the efficacy and safety data of this drug in the long-term management of hyperkalemia are scarce. During the last decade, two novel orally administered K+-exchanging compounds (patiromer and sodium-zirconium-cyclosilicate) have been approved for the treatment of adults with hyperkalemia, as they both effectively reduce elevated serum K+ and maintain chronically K+ balance within the normal range with an excellent tolerability and no serious adverse events.

Relapse of Monoclonal Gammopathy of Renal Significance after mRNA COVID-19 Vaccination: A Case Report.

This case report represents the first suspected case of light chain deposition disease relapse associated with mRNA COVID-19 vaccination. The 75-year-old female patient of Greek ethnicity was admitted to the clinic for the investigation of worsening renal function detected on routine lab examinations, two weeks after she received the second dose of the Moderna COVID-19 vaccine (mRNA-1273). Rapidly progressive glomerulonephritis and anemia were the most notable findings. She had a history of LCDD, which had remained stable for four years. Serum protein immunofixation showed monoclonal kappa zones, and a bone marrow biopsy revealed 5% plasma cell infiltration. These, along with other investigations, established the diagnosis of LCDD recurrence. The patient was started on chemotherapy, which improved her immunological profile, but not her renal function. The patient has remained on hemodialysis since. The association between mRNA vaccinations and LCDD relapse may be grounds for investigations into the pathophysiology of MGRS, given the patient's previous long-term remission. This case report is not intended to directly inform changes in clinical practice. We must stress the importance of following all standardized vaccination protocols, especially in immunocompromised patients.