Changes in right ventricular dimensions, function, and pulmonary circulation loading according to the degree of interdialytic weight gain in maintenance hemodialysis patients.

INTRODUCTION: The aim of this study was to investigate changes in echocardiographic right ventricular (RV) indices in relation to the degree of fluid accumulation between hemodialysis sessions, evaluated according to the recommended threshold of interdialytic-weight-gain corrected for dry weight (IDWG%). METHODS: A post-hoc analysis was performed using data from 41 maintenance hemodialysis patients. Patients were divided into a higher (>4.5%) and a lower (<4.5%) IDWG% group and underwent an echocardiographic assessment at the start and the end of the 3-day and the 2-day interdialytic interval. RESULTS: RV systolic pressure (RVSP) increments were more pronounced in the higher compared to the lower IDWG% group (16.43 ± 5.37 vs. 14.11 ± 13.38 mm Hg respectively, p = 0.015) over the 3-day interval, while changes in RV filling pressures, did not differ significantly between the groups (p = 0.84). CONCLUSIONS: During the 3-day interdialytic interval, pulmonary circulation is particularly overloaded in patients with fluid accumulation higher than the recommended thresholds, as evidenced by higher RVSP elevations.

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

BACKGROUND AND HYPOTHESIS: 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 (137mEq/L) compared to standard (140mEq/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 4 hemodialysis sessions with low (137mEq/L) followed by 4 sessions with standard (140mEq/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 SBP/DBP were significantly lower with low compared to standard dialysate sodium concentration (137.6±17.0/81.4±13.7mmHg with low vs 142.9±14.5/84.0±13.9mmHg with standard dialysate sodium, p=0.005/p=0.007 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±15.1mmHg with low vs 166.6±17.3/94.5±14.9mmHg with standard dialysate sodium, p<0.001/p=0.134 respectively) and intradialytic (141.4±18.0/85.0±13.4mmHg with low vs 147.5±13.6/88.1±12.5mmHg with standard dialysate sodium, p=0.034/p=0.013, 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.Registered at ClinicalTrials.gov with study number NCT05430438.

Uromodulin biology.

Uromodulin is a kidney-specific glycoprotein which is exclusively produced by the epithelial cells lining the thick ascending limb and early distal convoluted tubule. It is currently recognized as a multifaceted player in kidney physiology and disease, with discrete roles for intracellular, urinary, interstitial, and serum uromodulin. Among them, uromodulin modulates renal sodium handling through the regulation of tubular sodium transporters that reabsorb sodium and are targeted by diuretics, such as the loop diuretic-sensitive Na+-K+-2Cl- cotransporter type 2 (NKCC2) and the thiazide-sensitive Na+/Cl- cotransporter (NCC). Given these roles, the contribution of uromodulin to sodium-sensitive hypertension has been proposed. However, recent studies in humans suggest a more complex interaction between dietary sodium intake, uromodulin, and blood pressure. This review presents an updated overview of the uromodulin's biology and its various roles and focuses on the interaction between uromodulin and sodium-sensitive hypertension.

Effects of sodium-glucose co-transporter 2 inhibitors on heart failure events in chronic kidney disease: a systematic review and meta-analysis.

AIMS: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors significantly reduce the risk for hospitalizations for heart failure (HF) in patients with diabetes, and HF; findings in patients with chronic kidney disease (CKD) are not uniform. We aimed to perform a meta-analysis exploring the effect of SGLT-2 inhibitors on HF events in patients with CKD and across subgroups defined by baseline kidney function. METHODS AND RESULTS: A systematic search in major electronic databases was performed. Randomized controlled trials providing data on the effect of SGLT-2 inhibitors on the primary outcome, time to hospitalization or urgent visit for worsening HF in patients with prevalent CKD at baseline or across subgroups stratified by baseline estimated glomerular-filtration-rate (eGFR) were included. Twelve studies (n = 89,191 participants) were included in the meta-analysis. In patients with CKD, treatment with SGLT-2 inhibitors reduced the risk for HF events by 32% compared to placebo (hazard ratio [HR] 0.68; 95%CI 0.63-0.73). Reduction in HF events with SGLT-2 inhibitors was more prominent in patients with eGFR < 60 ml/min/1.73m2 (HR 0.68; 95%CI 0.62-0.74) than in those with eGFR ≥ 60 ml/min/1.73m2 (HR 0.76; 95%CI 0.69-0.83). Subgroup analysis according to type of SGLT-2 inhibitor showed a consistent treatment effect across all studied agents (p-subgroup-analysis = 0.44). Sensitivity analysis including data from studies including only diabetic patients showed an even more pronounced effect in eGFR subgroup < 60 ml/min/1.73m2 (HR 0.62; 95%CI 0.54-0.70). CONCLUSION: Treatment with SGLT-2 inhibitors led to a significant reduction in HF events in patients with CKD. Such findings may change the landscape of prevention of HF events in patients with advanced CKD. PROSPERO Registration number: CRD42022382857.

Autonomic Nervous System Dysfunction in Peritoneal Dialysis Patients: An Underrecognized Cardiovascular Risk Factor?

BACKGROUND: In patients with end-stage kidney disease (ESKD) receiving peritoneal dialysis (PD), cardiovascular events represent the predominant cause of morbidity and mortality, with cardiac arrhythmias and sudden death being the leading causes of death in this population. Autonomic nervous system (ANS) dysfunction is listed among the non-traditional risk factors accounting for the observed high cardiovascular burden, with a plethora of complex and not yet fully understood pathophysiologic mechanisms being involved. SUMMARY: In recent years, preliminary studies have investigated and confirmed the presence of ANS dysfunction in PD patients, while relevant results from cohort studies have linked ANS dysfunction with adverse clinical outcomes in these patients. In light of these findings, ANS dysfunction has been recently receiving wider consideration as an independent cardiovascular risk factor in PD patients. The aim of this review was to describe the mechanisms involved in the pathogenesis of ANS dysfunction in ESKD and particularly PD patients and to summarize the existing studies evaluating ANS dysfunction in PD patients. KEY MESSAGES: ANS dysfunction in PD patients is related to multiple complex mechanisms that impair the balance between SNS/PNS, and this disruption represents a crucial intermediator of cardiovascular morbidity and mortality in this population.

Heart rate variability at rest and in response to stress: Comparative study between hemodialysis and peritoneal dialysis patients.

Cardiac arrhythmias and sudden death are the leading causes of mortality in end-stage kidney disease (ESKD). Autonomic nervous system (ANS) dysfunction contributes to this arrhythmogenic background. This study compared heart rate variability (HRV) indices between hemodialysis (HD) and peritoneal dialysis (PD) patients, both at rest and in response to mental and physical stimulation maneuvers. Thirty-four HD and 34 PD patients matched for age, sex, and dialysis vintage, and 17 age- and sex-matched controls were studied. ANS function was examined by linear and non-linear HRV indices. Heart rate was recorded continuously (Finometer-PRO) at rest and during ANS maneuvers (orthostatic, mental-arithmetic, sit-to-stand, handgrip exercise tests). At rest, no significant differences between HD and PD were observed in HRV (root mean square of successive differences [RMSSD]: HD = 57.1 ± 81.1 vs PD = 69.6 ± 113.4 ms; P = 0.792), except for detrended fluctuation analysis (DFA-α1) (HD = 0.87 ± 0.40 vs PD = 0.70 ± 0.20; P = 0.047). DFA-α1 was significantly lower in PD than controls (1.00 ± 0.33; P < 0.05). All HRV indices during the mental-arithmetic test (RMSSD: HD = 128.2 ± 346.0 vs PD = 87.5 ± 150.0 ms; P = 0.893) and the physical stress tests were similar between HD and PD. The standard deviation along the line-of-identity (SD2)/the standard deviation perpendicular to the line-of-identity (SD1) ratio during mental-arithmetic was marginally lower in HD and significantly lower in PD than controls (PD = 1.31 ± 0.47 vs controls = 1.79 ± 0.64; P < 0.05). Both dialysis groups presented similar patterns in HRV responses during orthostatic and handgrip exercise tests. After the sit-to-stand, RMSSD, SD1, SD2, and DFA-α2 were higher compared to rest only in HD (RMSSD = 57.1 ± 81.1 vs 126.7 ± 185.7 ms; P = 0.028), suggesting a greater difficulty of HD patients in recovering normal ANS function in response to physical stress. In conclusion, HRV indices at rest and after mental and physical stimulation did not differ between HD and PD; however, the ANS responses following the sit-to-stand test were more impaired in HD. These findings suggest that ANS dysfunction is not largely affected by dialysis modality, but small differences in normal ANS recovery may exist.

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.

Cerebral oxygenation during exercise deteriorates with advancing chronic kidney disease.

BACKGROUND: Cognitive impairment and exercise intolerance are common in chronic kidney disease (CKD). Cerebral perfusion and oxygenation play a major role in both cognitive function and exercise execution. This study aimed to examine cerebral oxygenation during a mild physical stress in patients at different CKD stages and controls without CKD. METHODS: Ninety participants (18 per CKD stage 2, 3a, 3b and 4 and 18 controls) underwent a 3-min intermittent handgrip exercise at 35% of their maximal voluntary contraction. During exercise, cerebral oxygenation [oxyhaemoglobin (O2Hb), deoxyhaemoglobin (HHb) and total haemoglobin (tHb)] was assessed by near-infrared spectroscopy. Indices of microvascular (muscle hyperaemic response) and macrovascular function (carotid intima-media thickness and pulse wave velocity (PWV)) and cognitive and physical activity status were also evaluated. RESULTS: No differences in age, sex and body mass index were detected among groups. The mini-mental state examination score was significantly reduced with advancing CKD stages (controls: 29.2 ± 1.2, stage 2: 28.7 ± 1.0, stage 3a: 27.8 ± 1.9, stage 3b: 28.0 ± 1.8, stage 4: 27.6 ± 1.5; P = .019). Similar trends were observed for physical activity levels and handgrip strength. The average response in cerebral oxygenation (O2Hb) during exercise was lower with advancing CKD stages (controls: 2.50 ± 1.54, stage 2: 1.30 ± 1.05, stage 3a: 1.24 ± 0.93, stage 3b: 1.11 ± 0.89, stage 4: 0.97 ± 0.80 µmol/l; P < .001). The average tHb response (index of regional blood volume) showed a similar decreasing trend (P = .003); no differences in HHb among groups were detected. In univariate linear analysis, older age, lower estimated glomerular filtration rate (eGFR), Hb, microvascular hyperaemic response and increased PWV were associated with poor O2Hb response during exercise. In the multiple model, eGFR was the only parameter independently associated with the O2Hb response. CONCLUSIONS: Brain activation during a mild physical task appears to decrease with advancing CKD as suggested by the smaller increase in cerebral oxygenation. This may contribute to impaired cognitive function and reduced exercise tolerance with advancing CKD.

Impact of public restrictive measures on hypertension during the COVID-19 pandemic: existing evidence and long-term implications.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first identified in December 2019 and emerged into an ongoing global pandemic. Both the pandemic itself and the associated public restrictive measures of social mobility established with different intensity over different periods in various countries have significantly affected the everyday activities and lifestyles of people all over the world. The impact of lockdown and quarantine measures on hypertension incidence and blood pressure (BP) control is an important topic that requires further investigation. The aim of this review is: a) to present the current evidence regarding the actual effects of public restrictive measures on BP levels and control, originating primarily from studies investigating the impact of public restrictive measures on BP control with the use of various BP phenotypes; b) to summarize the possible pandemic-related effects of factors known to affect BP levels, including both traditional (e.g. dietary habits including alcohol and sodium intake, body weight, smoking and physical activity) and non-traditional (e.g. sleep patterns, air pollution, environmental noise, delayed diagnosis and medication adherence) ones.

Renal artery stenting in the correct patients with atherosclerotic renovascular disease: time for a proper renal and cardiovascular outcome study?

Atherosclerotic renovascular disease (ARVD) represents the most common type of renal artery stenosis. In the last decade, a few large trials failed to demonstrate the superiority of standard medical therapy plus percutaneous transluminal renal angioplasty (PTRA) compared with medical therapy alone in lowering blood pressure levels or preventing adverse renal and cardiovascular outcomes in patients with ARVD. However, this issue remains controversial and an ongoing debate focusses on the benefits that selected patients could experience from renal revascularization procedures. In this regard, several pieces of observational data show that PTRA is associated with future cardiorenal benefits in patients presenting with high-risk ARVD phenotypes. Such evidence resulted in a progressive shift in relevant recommendations, with most recent not-graded suggestions supporting that revascularization should be offered in these high-risk subjects. Existing evidence clearly calls for a properly designed randomized controlled trial with selected patients presenting high-risk ARVD phenotypes, in order to confirm the superiority of PTRA versus non-invasive management in this patient group and objectively guide everyday clinical practice.

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.

Muscle Oxygenation and Microvascular Reactivity Across Different Stages of CKD: A Near-Infrared Spectroscopy Study.

RATIONALE & OBJECTIVE: Previous studies in chronic kidney disease (CKD) showed that vascular dysfunction in different circulatory beds progressively deteriorates with worsening CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with different stages of CKD versus controls. STUDY DESIGN: Observational controlled study. SETTING & PARTICIPANTS: 90 participants (18 per CKD stage 2, 3a, 3b, and 4, as well as 18 controls). PREDICTOR: CKD stage. OUTCOME: The primary outcome was muscle oxygenation at rest. Secondary outcomes were muscle oxygenation during occlusion-reperfusion and exercise, and muscle microvascular reactivity (hyperemic response). ANALYTICAL APPROACH: Continuous measurement of muscle oxygenation [tissue saturation index (TSI)] using near-infrared spectroscopy at rest, during occlusion-reperfusion, and during a 3-minute handgrip exercise (at 35% of maximal voluntary contraction). Aortic pulse wave velocity and carotid intima-media thickness were also recorded. RESULTS: Resting muscle oxygenation did not differ across the study groups (controls: 64.3% ± 2.9%; CKD stage 2: 63.8% ± 4.2%; CKD stage 3a: 64.1% ± 4.1%; CKD stage 3b: 62.3% ± 3.3%; CKD stage 4: 62.7% ± 4.3%; P=0.6). During occlusion, no significant differences among groups were detected in the TSI occlusion magnitude and TSI occlusion slope. However, during reperfusion the maximum TSI value was significantly lower in groups of patients with more advanced CKD stages compared with controls, as was the hyperemic response (controls: 11.2%±3.7%; CKD stage 2: 8.3%±4.6%; CKD stage 3: 7.8%±5.5%; CKD stage 3b: 7.3%±4.4%; CKD stage 4: 7.2%±3.3%; P=0.04). During the handgrip exercise, the average decline in TSI was marginally lower in patients with CKD than controls, but no significant differences were detected across CKD stages. LIMITATIONS: Moderate sample size, cross-sectional evaluation. CONCLUSIONS: Although no differences were observed in muscle oxygenation at rest or during occlusion, the microvascular hyperemic response during reperfusion was significantly impaired in CKD and was most prominent in more advanced CKD stages. This impaired ability of microvasculature to respond to stimuli may be a crucial component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance. PLAIN-LANGUAGE SUMMARY: Previous studies in chronic kidney disease (CKD) have shown that vascular dysfunction in different circulatory beds progressively deteriorates with CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with nondialysis CKD versus controls, as well as across different CKD stages. It showed that the microvascular hyperemic response after an arterial occlusion was significantly impaired in CKD and was worst in patients with more advanced CKD. No significant differences were detected in skeletal muscle oxygenation or muscle oxidative capacity at rest or during the handgrip exercise when comparing patients with CKD with controls or comparing across CKD stages. The impaired ability of microvasculature to respond to stimuli may be a component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance.

Effect of patient gender on short-term blood pressure variability in hemodialysis patients.

Increased blood pressure variability (BPV) is strongly associated with cardiovascular events in end-stage kidney disease patients. Male hemodialysis patients present higher cardiovascular risk compared with females. The aim of this study is to investigate sex differences in short-term BPV in hemodialysis patients. 129 male and 91 female hemodialysis patients that underwent 48-h ABPM were included in this analysis. Standard deviation (SD), weighted SD (wSD), coefficient of variation (CV), and average real variability (ARV) of SBP and DBP were calculated with validated formulas. Age, dialysis vintage and history of major comorbidities did not differ between men and women. 48-h SBP/DBP (137.2 ± 17.4/81.9 ± 12.1 mmHg vs 132.2 ± 19.2/75.9 ± 11.7 mmHg, p = 0.045/<0.001) was significantly higher in men than women. During the 48-h period, all systolic BPV indices were similar between men and women (48-h SBP-ARV: 12.0 ± 2.9 vs 12.1 ± 3.2 mmHg, p = 0.683); 48-h DBP-SD, DBP-wSD and DBP-ARV (9.1 ± 1.6 vs 8.4 ± 1.8 mmHg, p = 0.005) were higher in men. In conclusion, short-term diastolic BPV indices are higher in male than female hemodialysis patients. Increased BPV may impact on the higher incidence of cardiovascular events observed in male hemodialysis patients.

Peridialytic and intradialytic blood pressure metrics are not valid estimates of 44-h ambulatory blood pressure in patients with intradialytic hypertension.

PURPOSE: In contrast to peridialytic blood pressure (BP), intradialytic and home BP measurements are accurate metrics of ambulatory BP load in hemodialysis patients. This study assessed the agreement of peridialytic, intradialytic, and scheduled interdialytic recordings with 44-h BP in a distinct hemodialysis population, patients with intradialytic hypertension (IDH). METHODS: This study included 45 IDH patients with valid 48-h ABPM and 197 without IDH. With 44-h BP used as reference method, we tested the accuracy of the following BP metrics: Pre- and post-dialysis, mean and median intradialytic, mean intradialytic plus pre/post-dialysis, and scheduled interdialytic BP (out-of-dialysis day: mean of 8:00am/8:00 pm readings). RESULTS: In IDH patients, peridialytic and intradialytic BP metrics showed at best moderate correlations, while averaged interdialytic SBP/DBP exhibited strong correlation (r = 0.882/r = 0.855) with 44-h SBP/DBP. Bland-Altman plots showed large between-method-difference for peri- and intradialytic-BP, but only + 0.7 mmHg between-method difference and good 95% limits of agreement for averaged interdialytic SBP. The sensitivity/specificity and κ-statistic for diagnosing 44-h SBP ≥ 130 mmHg were low for pre-dialysis (72.5/40.0%, κ-statistic = 0.074) and post-dialysis (90.0/0.0%, κ-statistic = - 0.110), mean intradialytic (85.0/40.0%, κ-statistic = 0.198), median intradialytic (85.0/60.0%, κ-statistic = 0.333), and intradialytic plus pre/post-dialysis SBP (85.0/20.0%, κ-statistic = 0.043). Averaged interdialytic SBP showed high sensitivity/specificity (97.5/80.0%) and strong agreement (κ-statistic = 0.775). In ROC analyses, scheduled interdialytic SBP/DBP had the highest AUC (0.967/0.951), sensitivity (90.0/88.0%), and specificity (100.0/90.0%). CONCLUSION: In IDH patients, only averaged scheduled interdialytic but not pre- and post-dialysis, nor intradialytic BP recordings show reasonable agreement with ABPM. Interdialytic BP recordings only could be used for hypertension diagnosis and management in these subjects.

Hemodialysis Effects on Autonomic Function: Results of Linear and Nonlinear Analysis of Heart Rate Variability at Rest and in Response to Physical and Mental Stress Tests.

INTRODUCTION: Cardiac arrhythmias are the most common cause of death in hemodialysis. Autonomic dysfunction plays a central role in this arrhythmogenic background. Previous studies on hemodialysis-related changes in heart rate variability (HRV) give contradictory results. This study investigated HRV indices both at rest and in response to physical and mental stimulation maneuvers at multiple time-points around and during the hemodialysis procedure. METHODS: Autonomic function was assessed by linear and nonlinear HRV indices at predialysis, during dialysis (3 equal time-periods), postdialysis, and on the nondialysis day in 36 hemodialysis patients. Continuous measurement of beat-by-beat heart rate was recorded with Finometer-PRO (The Netherlands) at rest and after orthostatic, sit-to-stand, handgrip, and mental-arithmetic test. RESULTS: The RMSSD, SD1, and SD2 indices significantly increased during dialysis (early-HD, mid-HD, late-HD periods) compared with the predialysis levels (p < 0.05) and returned to baseline postdialysis (RMSSD: 54.39 ± 83.73 vs. 137.98 ± 109.53* vs. 119.85 ± 97.34* vs. 144.47 ± 88.74* vs. 85.82 ± 121.43msec, *p < 0.05 vs. predialysis and postdialysis). No differences were detected in the above indices between the predialysis and nondialysis day. However, postdialysis, the HRV responses to orthostatic and sit-to-stand tests were more exaggerated than in the predialysis measurements (p < 0.05). The HRV responses both at resting and physical tests in the nondialysis day were similar to the predialysis levels. HRV indices in the mental arithmetic test during hemodialysis were much higher than at the nondialysis day (RMSSD: 77.05 [180.41] versus 19.75 [105.47] msec; p = 0.031). CONCLUSIONS: Hemodialysis causes marked changes in the autonomic function. Resting HRV indices return to baseline postdialysis, but HRV responses to physical stress remain exaggerated and return to baseline on the nondialysis day. Detecting patients with significant autonomic dysfunction may help towards reduction of arrhythmia risk through individualized approaches.

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.

Endothelial and microvascular function in liver cirrhosis: an old concept that needs re-evaluation?

Liver cirrhosis is characterized by significant circulatory dysregulation, related to an imbalance among several vasodilating agents, mainly nitric oxide. In contrast to portal vein and macrovascular hemodynamic alterations, which have been rather well described, the peripheral microcirculatory and endothelial structure and function in this population are less well studied. Endothelial dysfunction is characterized by an imbalance between endothelium-derived relaxing and contracting factors. A number of methods have been used to assess endothelial and microvascular function in human studies. Venous occlusion plethysmography was used for many years as the gold standard for evaluating endothelial function, but flow-mediated dilatation (FMD) of the forearm is currently the most frequently used method. In patients with cirrhosis, the few existing studies have mainly used FMD, but the relevant results are largely contradictory. In recent years, several noninvasive and easily applicable methods, such as near-infrared spectroscopy, laser speckle contrast imaging, peripheral arterial tonometry, optical coherence tomography and nailfold video-capillaroscopy, have been increasingly used to assess peripheral microvascular function and have demonstrated a number of advantages. In this review, we present functional methods to evaluate peripheral microvascular and endothelial function, and we discuss the existing evidence on circulatory dysfunction in patients with liver cirrhosis.

Management of intradialytic hypertension: current evidence and future perspectives.

Intradialytic hypertension (IDH), that is, a paradoxical rise in blood pressure (BP) during or immediately after a hemodialysis session, affects approximately 10-15% of the hemodialysis population. It is currently recognized as a phenomenon of major clinical significance as recent studies have shown that BP elevation extends to the whole interdialytic interval and associates with increased cardiovascular and all-cause mortality. The pathophysiology of IDH is complex involving volume and sodium overload, endothelial dysfunction, excess renin-angiotensin-aldosterone system and sympathetic nervous system activation, and other mechanisms. For several years, there was a scarcity of studies regarding IDH treatment; recently, however, several attempts to examine the effect of nonpharmacological and pharmacological measures on BP levels in IDH are made. This review attempts to summarize this latest evidence in the field of management of IDH and discuss areas for future research.