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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.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.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.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.

Kidney transplantation is considered the treatment of choice for end-stage kidney disease patients. However, the residual cardiovascular risk remains significantly higher in kidney transplant recipients (KTRs) than in the general population. Hypertension is highly prevalent in KTRs and represents a major modifiable risk factor associated with adverse cardiovascular outcomes and reduced patient and graft survival. Proper definition of hypertension and recognition of special phenotypes and abnormal diurnal blood pressure (BP) patterns is crucial for adequate BP control. Misclassification by office BP is commonly encountered in these patients, and a high proportion of masked and uncontrolled hypertension, as well as of white-coat hypertension, has been revealed in these patients with the use of ambulatory BP monitoring. The pathophysiology of hypertension in KTRs is multifactorial, involving traditional risk factors, factors related to chronic kidney disease and factors related to the transplantation procedure. In the absence of evidence from large-scale randomized controlled trials in this population, BP targets for hypertension management in KTR have been extrapolated from chronic kidney disease populations. The most recent Kidney Disease Improving Global Outcomes 2021 guidelines recommend lowering BP to less than 130/80 mmHg using standardized BP office measurements. Dihydropyridine calcium channel blockers and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers have been established as the preferred first-line agents, on the basis of emphasis placed on their favorable outcomes on graft survival. The aim of this review is to provide previous and recent evidence on prevalence, accurate diagnosis, pathophysiology and treatment of hypertension in KTRs.

Introduction Kidney transplantation (KTx) is associated with improved blood pressure (BP) levels for kidney transplant recipients (KTRs) without evoking significant changes in donors. However, there is a paucity of studies offering simultaneous detailed evaluation of BP profiles over time in transplant donor–recipient pairs. The aim of the present study was the parallel evaluation of ambulatory BP levels and trajectories in KTRs and their respective living kidney donors in the short and mid-term following KTx. Methods The study enrolled 40 prospective adult KTRs and their 40 respective donors. All participants were evaluated with 24-h ambulatory BP monitoring (Mobil-O-Graph NG device) at three time points: baseline (1 month before KTx), 3 months and 12 months after KTx. Results In KTRs, 3-month 24-h systolic BP (SBP) was marginally reduced and 12-month 24-h SBP significantly reduced compared with baseline [131.9 ± 13.3 versus 126.4 ± 11.9 mmHg (P = .075) and 123.9 ± 10.3 mmHg (P = .009), respectively]. At both the 3- and 12-month time points, 24-h diastolic BP (DBP) was significantly reduced [86.7 ± 11.5 versus 82.2 ± 8.1 mmHg (P = .043) and 80.3 ± 8.5 mmHg (P = .009)]. Similar observations were made for day- and night time SBP and DBP. Repeated-measures analysis of variance (ANOVA) showed a significant gradual decrease over time in mean 24-h SBP [F(1.463, 39.505) = 3.616; P = .049, partial η2 = 0.118] and DBP [F(1.374, 37.089) = 11.34; P = .055, partial η2 = 0.116]. In contrast, in kidney donors, 24-h SBP [118.5 ± 11.6 versus 118.2 ± 12.8 mmHg (P = .626) and 119.2 ± 11.4 mmHg (P = .748)] and DBP did not change at 3 or 12 months compared with baseline; repeated measures ANOVA showed no differences in the mean 24-h SBP and DBP levels over time. The number of antihypertensive agents decreas in KTRs and remained stable in donors. Conclusions KTx reduces ambulatory BP levels and trajectories in KTRs at 3 months and further so at 12 months post-surgery. Kidney donation does not affect the ambulatory BP levels and trajectories of donors at the same intervals.

Diabetic kidney disease (DKD) represents a major public health issue, currently posing an important burden on healthcare systems. Renin–angiotensin system (RAS) blockers are considered the cornerstone of treatment of albuminuric DKD. However, a high residual risk of progression to more advanced CKD stages under RAS blockade still remains, while relevant studies did not show significant declines in cardiovascular events with these agents in patients with DKD. Among several other pharmacological classes, mineralocorticoid receptor antagonists (MRAs) have received increasing interest, due to a growing body of high-quality evidence showing that spironolactone and eplerenone can significantly lower blood pressure and albuminuria in patients with CKD. Furthermore, finerenone, a novel nonsteroidal MRA with unique physicochemical properties, was shown to effectively reduce cardiovascular events and death, as well as the incidence of end-stage kidney disease in patients with type 2 diabetes. This review discusses previous and recent clinical evidence on the issue of nephroprotection and cardioprotection in DKD offered by mineralocorticoid receptor antagonism, aiming to aid clinicians in their treatment decisions for diabetic patients.

As our therapeutic armamentarium for HFpEF is insufficient, research has been focusing on the potential beneficial effect of existing pharmaceutical regimens on this specific patient population. A series of RCTs have recently examined the impact of various pharmaceutical treatments with proven benefit in HFrEF, on the improvement of symptoms of HFpEF patients. This systematic review and meta-analysis comprised studies of adult patients with HFpEF and evaluated the impact of different cardiovascular acting medication on cardiorespiratory fitness, reflected by peak VO

In this case, we report a 64-year-old man presenting with anorexia, nausea and vomiting, mild abdominal pain, and oligoanuria for a few hours. His previous medical history included diabetes, hypertension, and chronic kidney disease (CKD) stage 3. Upon arrival, laboratory results revealed stage III acute kidney injury (AKI) with hyperkalemia requiring dialysis treatment. During hospitalization, both pre-renal and post-renal causes of AKI were excluded, and a careful diagnostic evaluation, including kidney biopsy and serology testing, revealed acute interstitial nephritis and positive IgM for hantavirus. The patient was started on steroid treatment, which led to complete recovery of kidney function over 3 months. Moreover, during his hospitalization, the patient was also diagnosed with SARS-CoV-2 infection, possibly due to intra-hospital transmission and was hospitalized at the COVID-19 Department for 14 days, eventually with no further complications. Hantavirus nephropathy should be at the differential diagnosis of AKI, even in the absence of typical symptoms. Steroid treatment may be helpful in reversal of kidney injury.

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 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.

Hypertension and chronic kidney disease (CKD) are among the most common comorbidities associated with coronavirus disease 2019 (COVID-19) severity and mortality risk. Renin–angiotensin system (RAS) blockers are cornerstones in the treatment of both hypertension and proteinuric CKD. In the early months of the COVID-19 pandemic, a hypothesis emerged suggesting that the use of RAS blockers may increase susceptibility for COVID-19 infection and disease severity in these populations. This hypothesis was based on the fact that angiotensin-converting enzyme 2 (ACE2), a counter regulatory component of the RAS, acts as the receptor for severe acute respiratory syndrome coronavirus 2 cell entry. Extrapolations from preliminary animal studies led to speculation that upregulation of ACE2 by RAS blockers may increase the risk of COVID-19-related adverse outcomes. However, these hypotheses were not supported by emerging evidence from observational and randomized clinical trials in humans, suggesting no such association. Herein we describe the physiological role of ACE2 as part of the RAS, discuss its central role in COVID-19 infection and present original and updated evidence from human studies on the association between RAS blockade and COVID-19 infection or related outcomes, with a particular focus on hypertension and CKD.

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 ± 16.3/77.3 ± 9.4 vs. 126.4 ± 17.8/74.9 ± 11.5 mmHg; P = 0.118/0.104) but daytime SBP/DBP was significantly higher in men (128.5 ± 12.1/83.0 ± 8.2 vs. 124.6 ± 11.9/80.3 ± 9.3 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.

Cardiovascular disease is the leading cause of mortality in patients with end-stage-kidney disease. Evidence on the possible echocardiographic differences between hemodialysis and peritoneal dialysis (PD) is scarce. This study aimed to evaluate differences in left (LA) and right atrial (RA), left (LV) and right ventricular (RV) geometry, systolic and diastolic function in hemodialysis, and PD patients. Thirty-eight hemodialysis and 38 PD patients were matched for age, sex, and dialysis vintage. Two-dimensional and tissue-Doppler echocardiography, and lung ultrasound were performed during an interdialytic day in hemodialysis and before a programmed follow-up visit in PD patients. Vena cava diameter (11.09 ± 4.53 vs. 14.91 ± 4.30 mm; p < 0.001) was significantly lower in hemodialysis patients. Indices of LA, RA, LV, and RV dimensions were similar between the two groups. LVMi (116.91 [38.56] vs. 122.83 [52.33] g/m2 ; p = 0.767) was similar, but relative wall thickness was marginally (0.40 [0.14] vs. 0.45 [0.15] cm; p = 0.055) lower in hemodialysis patients. LV hypertrophy prevalence was similar between groups (73.7% vs. 71.1%; p = 0.798), but hemodialysis patients presented eccentric and PD patients concentric LVH. Regarding ventricular systolic function, stroke volume (p = 0.030) and cardiac output (p = 0.036) were higher in hemodialysis, while RV systolic pressure (RVSP) (20.37 [22.54] vs. 27.68 [14.32] mm Hg; p = 0.009) was higher in PD. No significant differences were evidenced in diastolic function indices and lung water excess between the two groups. A moderate association was noted between ultrasound B-lines score and LA volume index (r = 0.465, p < 0.001), RVSP (r = 0.431, p < 0.001), and E/e' ratio (r = 0.304, p = 0.009). Hemodialysis and PD patients present largely similar echocardiographic indices reflecting cardiac geometry, systolic, and diastolic function, but different patterns of abnormal LV remodeling.

Patients with kidney failure often present with reduced cardiovascular functional reserve and exercise tolerance. Previous studies on cardiorespiratory fitness examined with cardiopulmonary exercise testing (CPET) in kidney transplant recipients (KTR) had variable results. This is a systematic review and meta-analysis of studies examining cardiovascular functional reserve with CPET in KTR in comparison with patients with kidney failure (CKD-Stage-5 before dialysis, hemodialysis or peritoneal dialysis), as well as before and after kidney transplantation. Literature search involved PubMed, Web-of-Science and Scopus databases, manual search of article references and grey literature. From a total of 4,944 identified records, eight studies (with 461 participants) were included in quantitative analysis for the primary question. Across these studies, KTR had significantly higher oxygen consumption at peak/max exercise (VO2 peak/VO2 max) compared to patients with kidney failure (SMD = 0.70, 95% CI [0.31, 1.10], I2 = 70%, P = 0.002). In subgroup analyses, similar differences were evident among seven studies comparing KTR and hemodialysis patients (SMD = 0.64, 95% CI [0.16, 1.12], I2 = 65%, P = 0.009) and two studies comparing KTR with peritoneal dialysis subjects (SMD = 1.14, 95% CI [0.19, 2.09], I2 = 50%, P = 0.16). Across four studies with relevant data, oxygen consumption during peak/max exercise showed significant improvement after kidney transplantation compared to pretransplantation values (WMD = 2.43, 95% CI [0.01, 4.85], I2 = 68%, P = 0.02). In conclusion, KTR exhibit significantly higher cardiovascular functional reserve during CPET compared to patients with kidney failure. Cardiovascular reserve is significantly improved after kidney transplantation in relation to presurgery levels.

OBJECTIVES Hypertension is highly prevalent and independently associated with adverse outcomes in patients undergoing hemodialysis. Volume overload is the main mechanism of increased blood pressure (BP) in these individuals. This study examines the long-term effects of dry-weight reduction with a standardized lung-ultrasound (US)-guided strategy on ambulatory BP in hypertensive hemodialysis patients. METHODS This is the report of the 12-month follow-up of a randomized controlled trial in 71 clinically euvolemic, hemodialysis patients with hypertension. Patients were randomized to dry-weight reduction guided by prehemodialysis lung ultrasound and to standard care. A 48-h ambulatory BP monitoring (ABPM) was performed in all study participants at baseline and after 12 months. RESULTS During follow-up, a greater proportion of patients in the active group underwent dry-weight reduction compared with the control group (71.4% vs. 22.2%; P

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.

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.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.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.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.

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.

Ambulatory blood pressure (BP) control is worse in men than women with chronic kidney disease or kidney transplantation. So far, no study investigated possible sex differences in the prevalence, control, and phenotypes of BP according to predialysis and 48-h ambulatory blood pressure monitoring (ABPM) in hemodialysis patients. Further, no study has evaluated the diagnostic accuracy of predialysis BP in male and female hemodialysis patients.One hundred and twenty-nine male and 91 female hemodialysis patients that underwent 48-h ABPM were included in this analysis. Hypertension was defined as: (1) predialysis SBP ≥140 or DBP ≥90 mmHg or use of antihypertensive agents, (2) 48-h SBP ≥130 or DBP ≥80 mmHg or use of antihypertensive agents.Predialysis SBP did not differ between groups, while DBP was marginally higher in men. 48-h SBP (137.2 ± 17.4 vs. 132.2 ± 19.2 mmHg, P = 0.045), DBP (81.9 ± 12.1 vs. 75.9 ± 11.7 mmHg, P 0.001) and daytime SBP/DBP were higher in men. The prevalence of hypertension was not different between groups with the use of predialysis BP or 48-h ABPM (92.2% vs. 89%, P = 0.411). However, concordant lack of control was more frequent in men than women (65.3% vs. 49.4%, P = 0.023). The prevalence of white-coat and masked hypertension did not differ between groups; the misclassification rate with the use of predialysis BP was marginally higher in women. In both sexes, predialysis BP showed low accuracy and poor agreement with ABPM for diagnosing ambulatory hypertension [area-under-the-curve in receiver-operating-curve analyses (SBP/DBP): men, 0.681/0.802, women: 0.586/0.707].Ambulatory BP levels are higher in male than female hemodialysis patients. Although hypertension prevalence is similar between sexes, men have worse rates of control. The diagnostic accuracy of predialysis BP was equally poor in men and women.

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.Observational controlled study.90 participants (18 per CKD stage 2, 3a, 3b, 4, and 18 controls).CKD stage.Primary, muscle oxygenation at rest; secondary, muscle oxygenation during occlusion-reperfusion and exercise, and muscle microvascular reactivity (hyperemic response).Continuous measurement of muscle oxygenation [tissue saturation index (TSI%)] using near-infrared-spectroscopy at rest, during occlusion-reperfusion, and during a 3-min handgrip exercise (at 35% of maximal-voluntary-contraction). Aortic pulse-wave-velocity (PWV) and carotid intima-media thickness (cIMT) were also recorded.Resting muscle oxygenation did not differ across the study groups (controls: 64.3±2.9 stage-2: 63.8±4.2 stage-3a: 64.1±4.1 stage-3b: 62.3±3.3 stage-4: 62.7±4.3%; p=0.6). During occlusion, no significant differences among groups were detected in TSIModerate sample size, cross-sectional evaluation.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.

Introduction: Hypertension is the most prominent risk factor in kidney transplant recipients (KTRs). No study so far assessed in parallel the prevalence, control, and phenotypes of blood pressure (BP) or the accuracy of currently recommended office BP diagnostic thresholds in diagnosing elevated ambulatory BP in KTRs. Methods: 205 stable KTRs underwent office BP measurements and 24-h ambulatory BP monitoring (ABPM). Hypertension was defined as follows: (1) office BP ≥140/90 mm Hg or use of antihypertensive agents following the current European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines, (2) office BP ≥130/80 mm Hg or use of antihypertensive agents following the current American College of Cardiology/American Heart Association (ACC/AHA) guidelines, (3) ABPM ≥130/80 mm Hg or use of antihypertensive agents, and (4) ABPM ≥125/75 mm Hg or use of antihypertensive agents. Results: Hypertension prevalence by office BP was 88.3% with ESC/ESH and 92.7% with ACC/AHA definitions compared to 94.1 and 98.5% at relevant ABPM thresholds. Control rates among hypertensive patients were 69.6 and 43.7% with office BP compared to 38.3 and 21.3% with ABPM, respectively. Both for prevalence (κ-statistics = 0.52, p < 0.001 and 0.32, and p < 0.001) and control rates (κ-statistics = 0.21, p < 0.001 and 0.22, and p < 0.001, respectively), there was moderate or fair agreement of the 2 techniques. White-coat and masked hypertension were diagnosed in 6.7 and 39.5% of patients at the 140/90 threshold and 5.9 and 31.7% of patients at the 130/80 threshold. An office BP ≥140/90 mm Hg had 35.3% sensitivity and 84.9% specificity for the diagnosis of 24-h BP ≥130/80 mm Hg. An office BP ≥130/80 mm Hg had 59.7% sensitivity and 73.9% specificity for the diagnosis of 24-h BP ≥125/75 mm Hg. Receiver operating curve analyses confirmed this poor diagnostic performance. Conclusions: At both corresponding thresholds studied, ABPM revealed particularly high hypertension prevalence and poor BP control in KTRs. Misclassification of KTRs by office BP is substantial, due to particularly high rates of masked hypertension. The diagnostic accuracy of office BP for identifying elevated ambulatory BP is poor. These findings call for a wider use of ABPM in KTRs.

BACKGROUND AND AIMS Ambulatory blood pressure (BP) control is worse in men than in women with chronic kidney disease or kidney transplantation. So far no study assessed in parallel possible effects of sex differences on the prevalence, control and BP phenotypes according to pre-dialysis and 48-h ABPM in hemodialysis patients. Further, no study has evaluated the diagnostic accuracy of pre-dialysis BP levels in men and women hemodialysis patients. METHOD 129 male and 91 female hemodialysis patients that underwent 48-h ABPM with Mobil-O-Graph-NG were included in this analysis. Hypertension was defined as follows: (1) pre-dialysis BP ≥ 140/90 mmHg or use of antihypertensive agents, (2) 48-h BP ≥ 130/80 mmHg or use of antihypertensive agents. RESULTS The prevalence of hypertension was not different between men and women with the use of pre-dialysis BP (92.2% versus 92.3%, P = 0.987, respectively) or 48-h ABPM (92.2% versus 89%, P = 0.411). With the use of pre-dialysis BP men had significantly lower control rates than women (18.5% versus 32.1%, P = 0.025); a similar pattern of worse control in men was apparent with the use of ABPM, but the difference was not statistically significant (22.7% versus 28.4%, P = 0.360). The rate of patients with concordant lack of control by pre-dialysis and ABPM readings was significantly higher in men than women (65.3% versus 49.4%, P = 0.023); white-coat (14.9% versus 17.6%, P = 0.593) and masked hypertension (10.7% versus 18.8%, P = 0.101) did not differ between groups. However, the misclassifation rate with the use of pre-dialysis BP was lower in men than women. There was moderate or at best fair agreement between pre-dialysis and ambulatory BP with regards to the prevalence (men: κ-statistics = 0.39, P CONCLUSION The prevalence of hypertension is similar between men and women hemodialysis patients, but men have worse rates of office BP control. The diagnostic accuracy of pre-dialysis BP levels was equally poor in men and women hemodialysis patients.

BACKGROUND AND AIMS Hypertension is the most prevalent cardiovascular risk factor in kidney transplant recipients (KTRs). Preliminary data suggest similar ambulatory blood pressure (ΒP) levels in KTRs and hemodialysis (HD) patients. This is the first study evaluating in comparison the full ambulatory BP profile and short-term BP variability (BPV) in KTRs versus HD patients. METHOD Two hundred four 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 period of a standard 48-h ABPM in HD. To evaluate the effect of renal replacement treatment and time on ambulatory BP levels, two-way-ANOVA for repeated-measurements was performed. RESULTS KTRs had significantly lower SBP and pulse-pressure (PP) levels compared with HD 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 CONCLUSION SBP and PP levels and trajectories, and BPV were significantly lower in KTRs compared to age- and gender-matched HD patients during all periods studied. These findings suggest a more favorable ambulatory BP profile in KTRs, in contrast with previous observations.

BACKGROUND AND AIMS In contrast with pre- and post-dialysis 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 interdialytic BP in a distinct hemodialysis population, patients with intradialytic-hypertension (IDH). METHOD 45 patients with IDH (defined as: SBP rise ≥ 10 mmHg from pre- to post-dialysis and post-dialysis SBP ≥ 150 mmHg) with valid 48-h ABPM and 197 without IDH were included in this analysis. With 44-h BP used as reference method, we tested the accuracy of the following BP metrics: Pre- and post-dialysis, intradialytic, intradialytic plus pre/post-dialysis readings and scheduled interdialytic BP (out-of-dialysis day: readings at 8:00 am, 8:00 pm or their average). RESULTS In patients with IDH, peri-dialytic 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), intradialytic (85.0%/40.0%, κ-statistic = 0.198) and intradialytic plus pre/post-dialysis SBP (85.0%/20.0%, κ-statistic = 0.043). Averaged-interdialytic-SBP showed high values of sensitivity/specificity (97.5%/80.0%) and strong agreement (κ-statistic = 0.775). In ROC-analyses, the peri- and intradialytic BP metrics showed bad performance with low Area-Under-the-Curve values; scheduled interdialytic SBP/DBP had the largest AUC (0.967/0.951), along with the highest sensitivity(90.0%/88.0%) and specificity(100.0%/90.0%) for detecting elevated 44-h BP. CONCLUSION In patients with IDH, averaged-scheduled-interdialytic but not pre- and post-dialysis, nor intradialytic BP recordings show reasonable agreement with ambulatory BP. Interdialytic BP recordings only could be used for hypertension diagnosis and management in these subjects.

BACKGROUND AND AIMS Cognitive impairment and reduced exercise tolerance are common in patients with chronic kidney disease (CKD), in part due to reduced brain function. Proper brain function relies on sufficient blood flow and oxygen supply by the cerebral vasculature. A reduction in cerebral oxygenation of more than 10% may deteriorate brain function and influence the decision to continue exercise. This study aims to examine the cerebral oxygenation and blood volume during a mild physical stress as an index of brain activation in patients at different stages of CKD and controls without CKD. METHOD This is a preliminary analysis of an observational study enrolling patients with CKD stage 2–4 (matched for age and sex within the different stages) and controls without CKD. All participants underwent a 3-min intermittent handgrip exercise (HG) at 35% of their maximal voluntary contraction. Changes in prefrontal oxygenation (oxyhaemoglobin—O2Hb) and deoxyhaemoglobin—HHb) and total blood volume (total hemoglobin—tHb) were continuously recorded during HG-exercise by near-infrared spectroscopy (NIRS). RESULTS A total of 59 participants are included in this preliminary analyses (n = 11 controls, n = 15 stage 2 CKD, n = 18 stage 3 CKD and n = 15 stage 4 CKD patients). During HG-exercise, O2Hb significantly increased (P CONCLUSION Brain activation/response during a mild physical task appears to decrease with advancing CKD as suggested by the smaller rise in cerebral oxygenation and blood volume. This may contribute both impaired cognitive function and reduced exercise tolerance with advancing CKD.

BACKGROUND AND AIMS Ambulatory blood pressure (BP) control is worse in men than in women with chronic kidney disease (CKD), and this may partially explain the faster CKD progression in men. The aim of this study is to investigate possible sex-differences in ambulatory BP levels, BP trajectories and BP variability (BPV) in hemodialysis patients. METHOD 129 male and 91 female hemodialysis patients that underwent 48-h ABPM with Mobil-O-Graph-NG were included in this analysis. Ambulatory BP levels over the 2-day interdialytic interval (including two daytime and two nighttime periods) were recorded. We calculated the standard deviation (SD), weighted SD (wSD), coefficient of variation (CV) and average real variability (ARV) of BP with validated formulas. RESULTS Age, dialysis vintage, antihypertensive treatment and history of major comorbidities did not differ between men and women. Pre-dialysis SBP levels did not differ between men and women (145.1 ± 22.7 versus 145.9 ± 25.7 mmHg, P = 0.808), but DBP was marginally higher in men (87.6 ± 14.0 versus 84.0 ± 13.7 mmHg, P =0.055). About 48-h SBP/DBP (137.2 ± 17.4/81.9 ± 12.1 mmHg versus 132.2 ± 19.2/75.9 ± 11.7 mmHg, P = 0.045/ CONCLUSION Ambulatory BP levels and trajectories, as well as DBP variability indices are higher in men than women hemodialysis patients. This worse ambulatory BP profile in male compared to female patients may impact on the incidence of cardiovascular events.

BACKGROUND AND AIMS Patients with intradialytic hypertension (IDH) have higher mean 44-h ambulatory blood pressure (BP) levels than patients without the phenomenon. IDH is associated with an increased risk of cardiovascular and all-cause mortality. Whether the excess risk for mortality in patients with IDH depends on the BP rise during dialysis per se or on elevated 44-h ambulatory BP is not known. This is the first study evaluating the association of IDH with cardiovascular events and all-cause mortality before and after adjustment for ambulatory BP and other cardiovascular risk factors. METHOD A total of 242 haemodialysis patients underwent 48-h ABPM with Mobil-O-Graph-NG and were followed for a median of 45.7 months. IDH was defined as: SBP rise ≥ 10 mmHg from pre- to post-dialysis and post-dialysis SBP ≥ 150 mmHg. The primary end-point was all-cause mortality; the secondary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, resuscitation after cardiac arrest, hospitalization for heart failure, coronary or peripheral revascularization procedures. RESULTS During follow-up, a total of 122 patients died; 69 due to cardiovascular causes. Cumulative freedom from both the primary and secondary endpoints was significantly lower for patients with IDH (log rank-P = 0.048/0.022, respectively). The risk for all-cause mortality was significantly higher for patients with IDH [HR = 1.566, 95% confidence interval (95% CI) (1.001, 2.450)]; similarly, the risk for the combined cardiovascular endpoint was higher for these individuals [HR = 1.675, 95% CI (1.071, 2.620)]. The observed associations attenuated after adjustment for 44-h SBP [all-cause mortality: HR = 1.529, 95% CI (0.952, 2.457)] and combined cardiovascular endpoint: HR = 1.388 95% CI (0.866, 2.225). After additional adjustment for age, interdialytic weight gain, dialysis vintage, 44-h pulse wave velocity, history of coronary artery disease, diabetes mellitus and heart failure the respective HRs were 1.409 [95% CI (0.851, 2.332)] and 1.435 [95% CI (0.879, 2.343)]. CONCLUSION Patients with IDH presented higher risk for death and cardiovascular outcomes. Sustained high BP levels during the 44-h interdialytic period and not only intradialytic BP rise per se may be participating in the excess risk of this condition.

BACKGROUND AND AIMS 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 hemodialysis patients and its prognostic power is better than office PWV. This is the first study comparing ambulatory central blood pressure (BP) and arterial stiffness parameters between patients with and without IDH. METHOD This study examined 45 patients with IDH (defined as: SBP rise ≥ 10 mmHg from pre- to post-dialysis and post-dialysis SBP ≥ 150 mmHg) in comparison 197 without IDH. All participants underwent 48-h ABPM with the Mobil-O-Graph-NG device; parameters of central hemodynamics [central systolic (cSBP) and diastolic BP (cDBP), pulse pressure (PP)], wave reflection [augmentation index (AIx) and pressure (AP)] and PWV were estimated. RESULTS Age, dialysis vintage, interdialytic weight gain and prevalence of major comorbidities did not differ between the two study groups. Patients with IDH had higher 44-h cSBP (131.6 ± 16.7 versus 119.3 ± 15.6, P CONCLUSION Patients with IDH have higher ambulatory central BP and increased arterial stiffness, as indicated by higher ambulatory cPP and PWV. Increased arterial stiffness could be a prominent factor associated with the high burden of cardiovascular disease in this population.

Background Endothelial dysfunction is associated with cardiovascular events and mortality in various disease states, including end-stage renal disease (ESRD). Novel technological approaches have emerged for real-time assessment of endothelial reactivity. This study examined skin microcirculation using laser speckle contrast imaging (LSCI) before and after arterial occlusion in ESRD patients undergoing haemodialysis (HD) or peritoneal dialysis (PD). Methods The 38 HD patients were matched in a 1:1 ratio with 38 PD patients (for age, sex and dialysis vintage) and 38 controls (for age and sex). Skin microvascular reactivity parameters assessed with LSCI included baseline perfusion, occlusion perfusion and peak perfusion during post-occlusive reactive hyperaemia (PORH); time to peak perfusion; proportional change from baseline to peak perfusion; baseline and peak cutaneous vascular conductance (CVC); proportional change from baseline to peak CVC and amplitude of the PORH response (i.e. the difference between peak and baseline CVC). Results Baseline perfusion [HD: 46.97 ± 14.6; PD: 49.32 ± 18.07; controls: 42.02 ± 11.94 laser specle perfusion units (LSPU), P = 0.097] and peak post-occlusion perfusion (104.77 ± 28.68 versus 109.04 ± 40.77 versus 116.96 ± 30.96 LSPU, P = 0.238) did not differ significantly between groups. However, the post-occlusive vascular response was completely different since the proportional increase from baseline to peak perfusion (HD: 133 ± 66; PD: 149 ± 125; controls: 187 ± 61%, P = 0.001) was significantly lower in ESRD patients and time to peak response was lower in HD but similar in PD patients compared with controls (HD: 7.24 ± 6.99; PD: 10.68 ± 9.45; controls: 11.11 ± 5.1 s, Kruskal–Wallis P = 0.003; pairwise comparisons: HD versus controls, P = 0.002; HD versus PD, P = 0.154; PD versus controls, P = 0.406). ESRD patients also had lower levels of peak CVC, indicating the maximum capillary recruitment (HD: 1.05 ± 0.3; PD: 1.07 ± 0.44; controls: 1.57 ± 0.52 LSPU/mmHg, P Conclusions Using this novel non-invasive technology, endothelial post-occlusive forearm skin vasodilatory response was found to be similar between HD and PD patients and significantly impaired compared with controls. Future studies are needed to assess the prognostic implications of this microcirculatory functional defect.

BACKGROUND Ambulatory pulse-wave velocity (PWV), augmentation pressure, and augmentation index (AIx) are associated with increased cardiovascular events and death in hemodialysis. The intermittent nature of hemodialysis generates a distinct ambulatory pattern, with a progressive increase of augmentation pressure and AIx during the interdialytic interval. No study so far has compared the ambulatory course of central hemodynamics and PWV between peritoneal dialysis and hemodialysis patients. METHODS Thirty-eight patients under peritoneal dialysis and 76 patients under hemodialysis matched in a 1 : 2 ratio for age, sex and dialysis vintage underwent 48-h ambulatory blood pressure (BP) monitoring with the oscillometric Mobil-O-Graph device. Parameters of central hemodynamics [central SBP, DBP and pulse pressure (PP)], wave reflection [AIx, heart rate-adjusted AIx; AIx(75) and augmentation pressure] and PWV were estimated from the 48-h recordings. RESULTS Over the total 48-h period, no significant differences were observed between peritoneal dialysis and hemodialysis patients in mean levels of central SBP, DBP, PP, augmentation pressure, AIx, AIx(75) and PWV. However, patients under peritoneal dialysis and hemodialysis displayed different trajectories in all the above parameters over the course of the recording: in peritoneal dialysis patients no differences were noted in central SBP (125.0 ± 19.2 vs. 126.0 ± 17.8 mmHg, P = 0.25), DBP, PP, augmentation pressure (13.0 ± 6.8 vs. 13.7 ± 7. mmHg, P = 0.15), AIx(75) (25.9 ± 6.9 vs. 26.3 ± 7.8%, P = 0.54) and PWV (9.5 ± 2.1 vs. 9.6 ± 2.1 m/s, P = 0.27) from the first to the second 24-h period of the recording. In contrast, hemodialysis patients showed significant increases in all these parameters from the first to second 24 h (SBP: 119.5 ± 14.4 vs. 124.6 ± 15.0 mmHg, P

It is unclear whether normal white blood cell (WBC) counts are predictive of subsequent mortality in hemodialysis patients. All patients aged 17 years or more, who initiated hemodialysis at a tertiary Hospital from January 2000 to August 2017 with a dialysis vintage of greater than 90 days and normal median WBC count of their first dialysis year were included in the study. They were followed until they died, transferred to other dialysis facilities, switched to peritoneal dialysis, received a renal transplant or reached the end of the study (August 31, 2018). Cox regression was used to estimate hazard ratios for mortality of tertiles of WBC counts, adjusting for baseline demographic, clinical and laboratory variables. 611 patients [median (interquartile range) age 65.2 (53.3–72.6) years, 62.4% male] were studied. During a median follow-up of 3.9 (1.6–7.2) years, 270 participants died. Patients in the mid- (6.25–7.73 × 103/μL, n = 203) and top-tertile (7.73–10.50 × 103/μL, n = 203) of normal WBC counts had significantly higher mortality than patients in the bottom-tertile (3.50–6.25 × 103/μL, n = 205). The adjusted hazard ratio for mortality relative to the bottom-tertile was 1.54, 95% confidence interval (CI) 1.05–2.25 and 2.20, 95% CI 1.46–3.32, for the mid- and top-tertiles, respectively. In hemodialysis patients, higher WBC count within the normal range is associated with increased long-term mortality. This finding is described for the first time and provides further insight into the clinical significance of a “normal” WBC count result in dialysis patients.

Background: The majority of patients undergoing peritoneal dialysis (PD) suffer from volume overload and this overhydration is associated with increased mortality. Thus, optimal assessment of volume status in PD is an issue of paramount importance. Patient symptoms and physical signs are often unreliable indexes of true hydration status. Summary: Over the past decades, a quest for a valid, reproducible, and easily applicable technique to assess hydration status is taking place. Among existing techniques, inferior vena cava diameter measurements with echocardiography and natriuretic peptides such as brain natriuretic peptide and N-terminal pro-B-type natriuretic peptide were not extensively examined in PD populations; while having certain advantages, their interpretation are complicated by the underlying cardiac status and are not widely available. Bioelectrical impedance analysis (BIA) techniques are the most studied tool assessing volume overload in PD. Volume overload assessed with BIA has been associated with technique failure and increased mortality in observational studies, but the results of randomized trials on the value of BIA-based strategies to improve volume-related outcomes are contradictory. Lung ultrasound (US) is a recent technique with the ability to identify volume excess in the critical lung area. Preliminary evidence in PD showed that B-lines from lung US correlate with echocardiographic parameters but not with BIA measurements. This review presents the methods currently used to assess fluid status in PD patients and discusses existing data on their validity, applicability, limitations, and associations with intermediate and hard outcomes in this population. Key Message: No method has proved its value as an intervening tool affecting cardiovascular events, technique, and overall survival in PD patients. As BIA and lung US estimate fluid overload in different compartments of the body, they can be complementary tools for volume status assessment.

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.

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-BP-monitoring (ABPM) is recommended for hypertension diagnosis and management in hemodialysis patients due to its strong association with outcomes. Intradialytic and scheduled interdialytic BP recordings show agreement with ambulatory BP. This study assesses in parallel the association of pre-dialysis, intradialytic, scheduled interdialytic and ambulatory BP recordings with cardiovascular events.We prospectively followed 242 hemodialysis patients with valid 48-h ABPMs for a median of 45.7 months to examine the association of pre-dialysis, intradialytic, intradialytic plus pre/post-dialysis readings, scheduled interdialytic BP, and 44-h ambulatory BP with outcomes. The primary end-point was a composite one, composed of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, resuscitation after cardiac arrest, hospitalization for heart failure, coronary revascularization procedure or peripheral revascularization procedure.Cumulative freedom from the primary end-point was significantly lower with increasing 44-h SBP (group 1, 120 mmHg, 64.2%; group 2, ≥ 120 to 130 mmHg 60.4%, group 3, ≥ 130 to 140 mmHg 45.3%; group 4, ≥ 140 mmHg 45.5%; logrank-p = 0.016). Similar were the results for intradialytic (logrank-p = 0.039), intradialytic plus pre/post-dialysis (logrank-p = 0.044), and scheduled interdialytic SBP (logrank-p = 0.030), but not for pre-dialysis SBP (logrank-p = 0.570). Considering group 1 as the reference group, the hazard ratios of the primary end-point showed a gradual increase with higher BP levels with all BP metrics, except pre-dialysis SBP. This pattern was confirmed in adjusted analyses. An inverse association of DBP levels with outcomes was shown with all BP metrics, which was no longer evident in adjusted analyses.Averaged intradialytic and scheduled home BP measurements (but not pre-dialysis readings) display similar prognostic associations with 44-h ambulatory BP in hemodialysis patients and represent valid metrics for hypertension management in these individuals.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) share major risk factors and mechanistic pathways for progression. Furthermore, either decreased glomerular filtration rate or increased albuminuria are major risk factors for cardiovascular events. Evidence from previous renal outcome trials in patients with proteinuric CKD showed that angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) effectively slow CKD progression, establishing these agents as fundamental CKD pharmacologic treatments. However, in all these trials and subsequent meta-analyses, ACEIs and ARBs did not significantly reduce cardiovascular events or mortality, indicating a high residual risk for CVD progression in individuals with CKD. In contrast to the above, several outcome trials with old and novel mineralocorticoid receptor-antagonists (MRAs) clearly suggest that these agents, apart from nephroprotection, offer important cardioprotection in this population. This article is an overview of previous and recent evidence on the effects of MRAs on cardiovascular outcomes in patients with CKD attempting to highlight a pathway able to improve both cardiovascular and renal prognosis in this population.

Aim The burden of several cardiovascular risk factors increases in parallel to renal function decline. Exercise intolerance is common in patients with chronic kidney disease (CKD) and has been associated with increased risk of adverse outcomes. Whether indices of cardiorespiratory capacity deteriorate with advancing CKD stages is unknown. Methods We conducted a systematic review and meta-analysis of studies assessing cardiorespiratory capacity in adult patients with pre-dialysis CKD using cardiopulmonary exercise testing (CPET) and reporting data for different stages. Our primary outcome was differences in peak oxygen uptake (VO2 peak) between patients with CKD Stages 2-3a and those with Stages 3b-5(pre-dialysis). Literature search was undertaken in PubMed, Web of Science and Scopus databases, and abstract books of relevant meetings. Quality assessment was undertaken with Newcastle-Ottawa-Scale. Results From 4944 records initially retrieved, 6 studies with 512 participants fulfilling our inclusion criteria were included in the primary meta-analysis. Peak oxygen uptake (VO2 peak) was significantly higher in patients with CKD Stages 2-3a versus those with Stages 3b-5(pre-dialysis) (weighted-mean-difference, WMD: 2.46, 95%CI[1.15, 3.78]). Oxygen consumption at ventilatory threshold (VO2 VT) was higher in Stages 2-3a compared to those with Stages 3b-5(pre-dialysis) (standardized-mean-difference, SMD: 0.59, 95%CI[0.06, 1.1), while no differences were observed for maximum workload and respiratory-exchange-ratio. A secondary analysis comparing patients with CKD Stages 2-3b and Stages 4-5(pre-dialysis), yielded similar results (WMD: 1.78, 95%CI[1.34, 2.22]). Sensitivity analysis confirmed the robustness of these findings. Conclusion VO2 peak and VO2 VT assessed with CPET are significantly lower in patients in CKD Stages 3b-5 compared to Stages 2-3a. Reduced cardiorespiratory fitness may be another factor contributing to cardiovascular risk increase with advancing CKD. This article is protected by copyright. All rights reserved.

Background: Reductions in albuminuria of more than 30% are considered a strong marker of delay of chronic kidney disease (CKD) progression. Single renin–angiotensin system (RAS) blockade represents the cornerstone of CKD treatment. However, as CKD progression still occurs, other nephroprotective options were explored; mineralocorticoid receptor antagonists (MRA) were tested with generally positive results. Methods: We conducted a systematic review and meta-analysis on the effects of MRAs on albuminuria/proteinuria, and adverse events, such as change in renal function and hyperkalemia incidence. A detailed search in electronic databases, clinical trial registries and grey literature was performed to retrieve randomized controlled trials (RCTs) in which administration of an MRA alone or on-top of ACEi/ARB was compared with placebo or active treatment. Results: Of the 45 initially identified reports, 31, with 2767 participants, were included in analysis of the primary outcome. The use of MRAs (alone or on top of RAS blockade) compared with placebo decreased urine albumin-to-creatinine ratio (UACR) by −24.55% (95% CI −29.57 to −19.53%), urine protein-to-creatinine ratio (UPCR) by −53.93% (95% CI −79% to −28.86%) and 24 h albumin excretion by −32.47% (95% CI −41.1 to −23.85%). MRAs also reduced UACR by −22.48% (95% CI −24.51 to −20.44%) compared with calcium-channel-blockers (CCBs), whereas no differences were found compared with a second ACEi/ARB or nonpotassium-sparing diuretics. Addition of an MRA was associated with change in estimated glomerular filtration rate (eGFR) of −2.38 ml/min per 1.73 m2 (95% CI −3.51 to −1.25), rise in potassium by 0.22 mEq/l (95% CI 0.16–0.28 mEq/l) and a 2.6-fold increase in hyperkalemia risk (RR 2.63, 95% CI 1.69–4.08) compared with placebo/active control. Conclusion: Use of MRAs alone or on top of RAS blockade confers important antiproteinuric effects in patients with CKD, with a slight increase in mean potassium levels. Sin financiación 4.171 JCR (2019) Q1, 13/65 Peripheral Vascular Disease 1.365 SJR (2019) Q1, 42/186 Physiology, 65/362 Cardiology and Cardiovascular Medicine, 21/139 Internal Medicine No data IDR 2019 UEM

Diabetic kidney disease is a serious microvascular complication of diabetes mellitus and the leading cause of end-stage renal disease in western countries. New therapeutic agents are needed to delay its onset and progression. Recent literature suggests that sodium-glucose cotransporter 2 (SGLT-2) inhibitors may have renoprotective effects. Our aim was to systematically review the effect of SGLT-2 inhibitors on albuminuria and proteinuria in patients with diabetes mellitus. Studies were identified by search in major electronic databases, clinical trial registers, and sources of gray literature. We included randomized controlled trials of currently approved SGLT-2 inhibitors with a duration of at least 12 weeks. The primary outcome was the between-groups difference in the proportional (%) change of albuminuria or proteinuria between baseline and end of treatment. SGLT-2 inhibitors were associated with statistically significant reduction in albuminuria compared to placebo or active control [weighted mean difference (WMD) -25.39%, 95% confidence interval (CI) -34.17 to -16.62] (15 studies, N = 17 540 patients). When trials were stratified according to the level of baseline albuminuria, reduction in urine albumin-to-creatinine ratio was more prominent in randomized controlled trials in patients with moderately (WMD -40.78%, 95% CI -63.21 to -18.34) or severely increased albuminuria (WMD -36.40%, 95% CI -51.53 to -21.26). Only one study reported data for urine protein-to-creatinine ratio. Finally, SGLT-2 inhibitors reduced systolic and diastolic blood pressure by 4.43 mmHg (95% CI -5.24 to -3.63) and 1.81 mmHg (95% CI -2.38 to -1.23), respectively.

Approximately 85% of hemodialysis patients are hypertensive, but less than 30% achieve adequate blood pressure (BP) control. Reduction of volume overload is fundamental for BP control, but clinical criteria to estimate dry-weight are inaccurate. In the present study we examined the effect of dry-weight reduction with a lung-ultrasound-guided strategy on ambulatory BP in 71 clinically euvolemic hemodialysis patients with hypertension. Patients were equally randomized into an active group, following a strategy for dry-weight reduction guided by pre-hemodialysis lung ultrasound, and a control group with standard-of-care treatment. All patients underwent 48-hour ambulatory BP monitoring (ABPM) at baseline and after eight weeks. Overall, more patients in the active than in the control group had dry weight reduction, 54.3% compared to 13.9%, respectively. The ultrasonographic-B line change during follow-up was significantly different (-5.3±12.5 in active versus +2.2±7.6 in control group), which corresponded to significant differences in dry weight changes between the groups. The magnitude of reductions in 48-hour systolic BP (-6.61±9.57 vs. -0.67±13.07) and diastolic BP (-3.85±6.34 vs. -0.55±8.28) was significantly greater in the active group. Similarly, intradialytic BP, 44-hour BP, and daytime or night-time systolic/diastolic BP during both days of the interdialytic interval were significantly reduced in the active group but remained unchanged in the control group. The percentage of patients experiencing one or more intradialytic hypotensive episodes was marginally lower in the active group (34.3% vs. 55.6%). Thus, a lung-ultrasound-guided strategy for dry-weight reduction can effectively and safely reduce ambulatory BP levels in hemodialysis patients. Clinical implementation of this simple technique can help increase BP control in this population.

Background: The use of single RAS-blockade is currently the recommended first-line treatment for proteinuric diabetic or non-diabetic nephropathy, as these agents were repeatedly shown in studies with hard renal outcomes to retard the progression of renal injury. However, CKD will continue to progress on optimum single RAS-blockade, and other options to ameliorate renal injury were explored. Dual RAS-blockade was associated with an increased risk of adverse-events with no apparent benefits and, therefore, is currently abandoned. : Based on the phenomenon of aldosterone escape and the well-documented harmful effects of aldosterone on renal tissue, several randomized trials have studied the effects of a MRA in diabetic and non-diabetic nephropathy. Method: This is a review of the literature in relevance to data evaluating the effect of MRA on renal outcomes. Results: Studies with spironolactone and eplerenone added to single RAS-blockade showed that these agents are associated with greater reductions in urine albumin or protein excretion compared to either placebo or dual RASblockade. However, studies with these agents on hard renal outcomes are currently missing and the reasonable skepticism of physicians on the real-world incidence of hyperkalemia in CKD patients are limiting their use. A non-steroidal MRA, finerenone, has also great potency in decreasing albuminuria in diabetic nephropathy with possibly lower rates of hyperkalemia. Two multi-center clinical trials examining the effect of finerenone on hard cardiovascular and renal outcomes are currently ongoing. Conclusion: MRAs are able to reduce albuminuria and proteinuria on top of single RAS-blockade in patients with proteinuric CKD. Ongoing clinical trials are expected to clarify whether such an effect is accompanied by delay in CKD progression.

Background Increased short-term blood pressure (BP) variability (BPV) in hemodialysis is associated with increased cardiovascular and all-cause mortality. Studies on the impact of BP-lowering interventions on BPV are scarce. This study examined the effect of dry-weight reduction with a lung ultrasound-guided strategy on short-term BPV in hemodialysis patients with hypertension. Methods This is a prespecified analysis of a randomized clinical trial in 71 hemodialysis patients with hypertension, assigned in a 1:1 ratio in the active group, following a strategy for dry-weight reduction guided by pre-hemodialysis lung ultrasound and the control group following standard-of-care treatment. All patients underwent 48-hour ambulatory BP monitoring at baseline and after 8 weeks. BPV was calculated with validated formulas for the 48-hour interval and the 2 daytime and nighttime periods. Results Dry-weight changes were –0.71 ± 1.39 in active vs. +0.51 ± 0.98 kg in the control group (P < 0.001), generating a between-group difference of 5.9/3.5 mm Hg (P < 0.05) in 48-hour BP at study end. All brachial BPV indices [SD, weighted SD, coefficient of variation, and average real variability (ARV)] did not change significantly from baseline to study end in the active [systolic blood pressure (SBP)-ARV: 12.58 ± 3.37 vs. 11.91 ± 3.13, P = 0.117; diastolic blood pressure (DBP)-ARV: 9.14 ± 1.47 vs. 8.80 ± 1.96, P = 0.190] or control (SBP-ARV: 11.33 ± 2.76 vs. 11.07 ± 2.51, P = 0.544; DBP-ARV: 8.38 ± 1.50 vs. 8.15 ± 1.49, P = 0.295) group (between-group comparison P = 0.211/0.117). Aortic BPV indices followed a similar pattern. Likewise, no significant changes in BPV indices for the daytime and nighttime periods were noted in both groups during follow-up. Conclusions This study is the first to evaluate the effects of a nonpharmacological intervention on short-term BPV in hemodialysis, showing no effect of dry-weight reduction on BPV, despite BP decrease.

Background Cardiovascular disease is a major cause of morbidity and mortality in COPD. Endothelial dysfunction is suggested to be one of the pathogenetic mechanisms involved. This is a systematic review and meta-analysis of studies using any available functional method to examine differences in endothelial function between patients with COPD and individuals without COPD (controls). Methods Literature search involved PubMed and Scopus databases. Eligible studies included adult patients and evaluated endothelial damage via functional methods. The Newcastle–Ottawa scale was applied to evaluate the quality of retrieved studies. Subgroup analyses were performed to explore heterogeneity across the studies. Funnel plots were constructed to evaluate publication bias. Results Of the 21 reports initially identified, 19 studies with a total of 968 participants were included in the final meta-analysis. A significantly impaired response in endothelium-dependent (weighted mean between-group difference (WMD) −2.59, 95% CI −3.75 to −1.42) and -independent vasodilation (WMD −3.13, 95% CI −5.18 to −1.09) was observed in patients with COPD compared to controls. When pooling all studies together, regardless of the technique used for assessment of vascular reactivity, pronounced endothelial dysfunction was observed in COPD compared to controls (standardised mean difference (SMD) −1.19, 95% CI −1.69 to −0.68). Subgroup analysis showed that the difference was larger when patients with COPD were compared with nonsmoking controls (SMD −1.75, 95% CI −2.58 to −0.92). Sensitivity analyses confirmed the results. Conclusions Patients with COPD have significantly impaired endothelial function compared to controls without COPD. Future studies should delineate the importance of endothelial dysfunction towards development of cardiovascular disease in COPD., COPD is significantly associated with endothelial dysfunction of both conduit vessels and microvasculature. This association is further strengthened when patients with COPD are compared to nonsmoking controls. https://bit.ly/2NlWLFN

Background and Aims Patients with chronic kidney disease (CKD) often present with reduced physical activity and exercise performance due to a number of factors relevant to co-existing disturbances of the cardiac, nervous and muscular systems. Cardiopulmonary exercise testing (CPET) is widely applied in daily clinical practice used for clinical evaluation of exercise intolerance and related symptoms (i.e. dyspnea, fatigue), as well risk stratification, and other applications in several medical fields. Method This is a systematic review and meta-analysis of studies which used CPET technology in adult patients with CKD to examine cardiopulmonary reserve in individuals with versus individuals without CKD. The primary outcome was peak oxygen uptake (VO2peak). Literature search involved PubMed, Web of Science and Scopus databases; manual search of article references and of grey literature was also performed. Newcastle-Ottawa Scale was applied to evaluate the quality of retrieved studies. Results From an initial 4944 literature records, we identified 29 studies fulfilling the inclusion criteria; of these, 25 studies with complete data including 2213 participants were included in final meta-analysis. Peak oxygen uptake (VO2peak) was significantly lower in CKD patients compared to controls without CKD (standardized-mean-difference, SMD:-1.40, 95%CI[-1.68, -1.13]) (Figure). Oxygen consumption at anaerobic threshold (VO2AT) (SMD:-1.06, 95%CI[-1.34, -0.79]), maximum workload (weighted-mean-difference, WMD:-58.26, 95%CI[-74.14, -42.38]) and respiratory exchange ratio (RER) (WMD:-0.02, 95%CI[-0.05, 0.01]) were also impaired in CKD patients compared to non-CKD individuals. In 3 studies comparing patients with CKD versus patients with heart failure without CKD VO2peak was higher in the former (WMD:6.60, 95%CI[3.02, 10.18]). Sensitivity analyses confirmed the robustness of these findings. Conclusion VO2peak and other commonly analyzed CPET variables were lower in CKD patients compared to controls, indicating reduced functional cardiopulmonary reserve in the former. In contrast, CKD patients performed better when compared patients with heart failure.