The association of home blood pressure with all-cause mortality in hemodialysis patients: A prospective observational study.

INTRODUCTION: Prior observational studies conducted in the hemodialysis population have suggested a reverse association between dialysis-unit blood pressure (BP) and mortality. The present study aimed to investigate the prognostic association of home versus dialysis-unit BP with all-cause mortality in hemodialysis patients. METHODS: At baseline, 146 patients receiving maintenance hemodialysis underwent assessment of their BP with the following methods: (i) 2-week averaged routine predialysis and postdialysis BP measurements; (ii) home BP monitoring for 1 week that included duplicate morning and evening BP measurements with the use of validated devices. RESULTS: Over a median follow-up period of 38 months (interquartile range [IQR]: 22-54), 44 patients (31.1%) died. In Kaplan-Meier curves, predialysis and postdialysis systolic BP (SBP) was not associated with all-cause mortality, while home SBP appeared to be of prognostic significance (log rank p = 0.029). After stratifying patients into quartiles, all-cause mortality was lowest when home SBP was ranging from 128.1 to 136.8 mmHg (quartile 2). In univariate Cox regression analysis, using quartile 2 as a referent category, the risk of all-cause mortality was 3.32-fold higher in quartile 1, 1.53-fold higher in quartile 3 and 3.25-fold higher in quartile 4. The risk-association remained unchanged after adjustment for several confounding factors (adjusted hazard ratio: 4.79, 1.79, 3.63 for quartiles 1, 3, and 4 of home systolic BP, respectively). CONCLUSION: Our findings suggest that among hemodialysis patients, 1-week averaged home SBP is independently associated with all-cause mortality. In sharp contrast, SBP recorded either before or after dialysis over 2 weeks is not prognostically informative.

Gender-Related Differences in the Levels of Ambulatory BP and Intensity of Antihypertensive Treatment in Patients Undergoing Peritoneal Dialysis.

Prior studies have shown that among patients with chronic kidney disease not yet on dialysis, the faster progression of kidney injury in men than in women is, at least partly, explained by sex differences in ambulatory blood pressure (BP) control. The present study aimed to investigate potential differences in the levels of ambulatory BP and intensity of antihypertensive treatment between men and women with end-stage kidney disease undergoing long-term peritoneal dialysis (PD). In a case-control design, 48 male PD patients were matched for age and heart failure status with 48 female patients in a 1:1 ratio. Ambulatory BP monitoring was performed with an oscillometric device, the Mobil-O-Graph (IEM, Stolberg, Germany). The BP-lowering medications actually taken by the patients were prospectively recorded. No gender-related differences were observed in 24 h systolic BP (129.0 ± 17.9 vs. 128.5 ± 17.6 mmHg, p = 0.890). In contrast, 24 h diastolic BP was higher in men than in women (81.5 ± 12.1 vs. 76.8 ± 10.3 mmHg, p = 0.042). As compared with women, men were being treated with a higher average number of antihypertensive medications daily (2.4 ± 1.1 vs. 1.9 ± 1.1, p = 0.019) and were more commonly receiving calcium-channel-blockers (70.8% vs. 43.8%, p = 0.007) and ß-blockers (85.4% vs. 66.7%, p = 0.031). In conclusion, the present study shows that among PD patients, the levels of ambulatory BP and intensity of antihypertensive treatment are higher in men than in women. Longitudinal studies are needed to explore whether these gender-related differences in the severity of hypertension are associated with worse cardiovascular outcomes for male patients undergoing PD.

Therapeutic Advances in Diabetic Kidney Disease.

Although sodium glucose co-transporter type 2 (SGLT-2) inhibitors were initially introduced as glucose-lowering medications, it was later discovered that cardiorenal protection is the most important treatment effect of these agents. A triad of landmark trials consistently showed the benefits of SGLT-2 inhibitors on kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD), irrespective of the presence or absence of Type 2 diabetes (T2D). Furthermore, finerenone is a novel, selective, nonsteroidal mineralocorticoid receptor antagonist (MRA) that safely and effectively improved cardiorenal outcomes in a large Phase 3 clinical trial program that included >13,000 patients with T2D and a wide spectrum of CKD. These two drug categories have shared and distinct mechanisms of action, generating the hypothesis that an overadditive cardiorenal benefit with their combined use may be biologically plausible. In this article, we describe the mechanism of action, and we provide an overview of the evidence for cardiorenal protection with SGLT-2 inhibitors and the nonsteroidal MRA finerenone in patients with CKD associated with T2D.

Effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on cardiovascular outcomes in dialysis patients: a systematic review and meta-analysis.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) are recommended by guidelines as first-line antihypertensive therapies in the general population or in patients with earlier stages of kidney disease. However, the cardioprotective benefit of these agents among patients on dialysis remains uncertain. METHODS: We searched the MEDLINE, PubMed and Cochrane databases from inception through February 2022 to identify randomized controlled trials (RCTs) comparing the efficacy of ACEIs/ARBs relative to placebo or no add-on treatment in patients receiving dialysis. RCTs were eligible if they assessed fatal or non-fatal cardiovascular events as a primary efficacy endpoint. RESULTS: We identified five RCTs involving 1582 dialysis patients. Compared with placebo or no add-on treatment, the use of ACEIs/ARBs was not associated with a significantly lower risk of cardiovascular events {risk ratio [RR] 0.79 [95% confidence interval (CI) 0.57-1.11]}. Furthermore, there was no benefit in cardiovascular mortality [RR 0.82 (95% CI 0.59-1.14)] and all-cause mortality [RR 0.86 (95% CI 0.64-1.15)]. These results were consistent when the included RCTs were stratified by subgroups, including hypertension, ethnicity, sample size, duration of follow-up and quality. CONCLUSION: The present meta-analysis showed that among patients on dialysis, the use of ACEIs/ARBs is not associated with a significantly lower risk of cardiovascular events and all-cause mortality as compared with placebo or no add-on treatment.

Hypertension in Dialysis Patients: Diagnostic Approaches and Evaluation of Epidemiology.

Whereas hypertension is an established cardiovascular risk factor in the general population, the contribution of increased blood pressure (BP) to the huge burden of cardiovascular morbidity and mortality in patients receiving dialysis continues to be debated. In a large part, this controversy is attributable to particular difficulties in the accurate diagnosis of hypertension. The reverse epidemiology of hypertension in dialysis patients is based on evidence from large cohort studies showing that routine predialysis or postdialysis BP measurements exhibit a U-shaped or J-shaped association with cardiovascular or all-cause mortality. However, substantial evidence supports the notion that home or ambulatory BP measurements are superior to dialysis-unit BP recordings in diagnosing hypertension, in detecting evidence of target-organ damage and in prognosticating the all-cause death risk. In the first part of this article, we explore the accuracy of different methods of BP measurement in diagnosing hypertension among patients on dialysis. In the second part, we describe how the epidemiology of hypertension is modified when the assessment of BP is based on dialysis-unit versus home or ambulatory recordings.

Prevalence of Apparent Treatment-Resistant Hypertension in ESKD Patients Receiving Peritoneal Dialysis.

BACKGROUND: Apparent treatment-resistant hypertension (aTRH) is defined as failure to achieve adequate blood pressure (BP) control despite taking ≥3 antihypertensive medications from different categories or when taking ≥4 antihypertensives regardless of BP levels. METHODS: In this cross-sectional study, we estimated the prevalence of aTRH in 140 patients receiving long-term peritoneal dialysis (PD) in four centers of Northern Greece, using the "gold-standard" method of ambulatory BP monitoring for the assessment of BP control status. The presence of subclinical overhydration was evaluated with the method of bioimpedance spectroscopy (BIS). RESULTS: Incorporating the diagnostic threshold of 130/80 mmHg for 24-hour ambulatory BP, the prevalence of aTRH in the overall study population was 30%. Compared to patients without aTRH, those with aTRH tended to be older in age, had higher PD vintage, had higher dialysate-to-plasma creatinine ratio, had more commonly history of diabetes mellitus, and were more commonly current smokers. With respect to the volume status, the overhydration index in BIS was higher in those with versus without aTRH (2.0 ±â€…1.9 L vs. 1.1 ±â€…2.0 L, P < 0.05). The prevalence of volume overload, defined as an overhydration index in BIS > 2.5 L, was also higher in the subgroup of patients with aTRH (38.1% vs. 18.4, P = 0.01). CONCLUSION: The present study showed that among patients on PD, the prevalence of aTRH was 30%. However, 38% of PD patients with aTRH had subclinical overhydration in BIS, suggesting that the achievement of adequate volume control may be a therapeutic opportunity to improve the management of hypertension in this high-risk patient population.The present study showed that among patients on PD, the prevalence of aTRH was 30%. However, 38% of PD patients with aTRH had subclinical overhydration in BIS, suggesting that the achievement of adequate volume control may be a therapeutic opportunity to improve the management of hypertension in this high-risk patient population. CLINICAL TRIALS REGISTRATION: Trial Number NCT03607747.

Feeding during Dialysis Increases Intradialytic Blood Pressure Variability and Reduces Dialysis Adequacy.

Whether hemodialysis patients should be allowed or even encouraged to eat during dialysis remains a controversial topic. This cross-over study aimed to evaluate the impact of feeding during dialysis on intradialytic blood pressure (BP) profile and dialysis adequacy in 26 patients receiving thrice-weekly, in-center hemodialysis. Over three consecutive mid-week dialysis sessions, intradialytic BP was monitored using the Mobil-O-Graph device (IEM, Stolberg, Germany). Blood samples were also obtained for the determination of the urea reduction ratio (URR). At baseline, patients underwent dialysis without the provision of a meal. In phases A and B, a meal with either high-protein (1.5 gr/kg of body weight) or low-protein (0.7 gr/kg of body weight) content was administered 1 h after the initiation of dialysis. The sequence of meals (high-protein and low-protein or vice versa) was randomized. Average intradialytic systolic BP (SBP) was similar on all three occasions. However, compared with baseline, the standard deviation (SD) (11.7 ± 4.1 vs. 15.6 ± 7.6 mmHg, p < 0.01), coefficient of variation (CV) (9.5 ± 3.7% vs. 12.4 ± 6.0%, p < 0.01) and average real variability (ARV) (9.4 ± 3.9 vs. 12.1 ± 5.2 mmHg, p < 0.01) of intradialytic SBP were higher in phase A. Similarly, compared with the baseline evaluation, all three indices of intradialytic SBP variability were higher in phase B (SD: 11.7 ± 4.1 vs. 14.1 ± 4.5 mmHg, p < 0.05; CV: 9.5 ± 3.7% vs. 11.1 ± 3.8%, p < 0.05; ARV: 9.4 ± 3.9 vs. 10.9 ± 3.9 mmHg, p < 0.05). Compared with dialysis without a meal, the consumption of a high-protein or low-protein meal resulted in a lower URR (73.4 ± 4.3% vs. 65.7 ± 10.7%, p < 0.001 in phase A and 73.4 ± 4.3% vs. 67.6 ± 4.3%, p < 0.001 in phase B, respectively). In conclusion, in the present study, feeding during dialysis was associated with higher intradialytic SBP variability and reduced adequacy of the delivered dialysis.

Vitamin K Supplementation for Prevention of Vascular Calcification in Chronic Kidney Disease Patients: Are We There Yet?

Chronic Kidney Disease (CKD) patients are at high risk of presenting with arterial calcification or stiffness, which confers increased cardiovascular mortality and morbidity. In recent years, it has become evident that VC is an active process regulated by various molecules that may act as inhibitors of vessel mineralization. Matrix Gla Protein (MGP), one the most powerful naturally occurring inhibitors of arterial calcification, requires vitamin K as a co-factor in order to undergo post-translational γ-carboxylation and phosphrorylation and become biologically active. The inactive form of MGP (dephosphorylated, uncarboxylated dp-ucMGP) reflects vitamin K deficiency and has been repeatedly associated with surrogate markers of VC, stiffness, and cardiovascular outcomes in CKD populations. As CKD is a state of progressive vitamin K depletion and VC, research has focused on clinical trials aiming to investigate the possible beneficial effects of vitamin K in CKD and dialysis patients. In this study, we aim to review the current evidence regarding vitamin K supplementation in uremic patients.

Evidence for Cardiorenal Protection with SGLT-2 Inhibitors and GLP-1 Receptor Agonists in Patients with Diabetic Kidney Disease.

For almost two decades, the management of patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) was based on the optimal glycemic and blood pressure control as well as on the adequate blockade of the renin-angiotensin-system. Over the past few years, sodium-glucose co-transporter 2 (SGLT-2) inhibitors and glucagone-like peptide 1 receptor agonists (GLP1-RAs) were added to our therapeutic armarhatum, offering promise for more effective mitigation of the substantial residual cardiorenal risk of these patients. Large randomized controlled trials (RCTs) designed to demonstrate the cardiovascular safety of SGLT-2 inhibitors and GLP1-RAs showed that these novel anti-diabetic medications improve cardiovascular outcomes in patients with T2DM. RCTs conducted specifically in CKD patients with or without T2DM demonstrated that SGLT-2 inhibitors were also effective in retarding the progression of kidney injury to end-stage kidney disease. The kidney protective effects of GLP1-RA are not yet proven, but RCTs are currently ongoing to investigate this crucial research question. In this article, we review the available clinical-trial evidence supporting the use of SGLT-2 inhibitors and GLP1-RAs for cardiorenal protection in patients with T2DM and CKD. We provide clinical practice recommendations for a personalized approach in the use of these novel therapies, according to the severity of CKD and the presence of other cardiometabolic risk factors.

Epidemiology of Hypertension among Patients on Peritoneal Dialysis Using Standardized Office and Ambulatory Blood Pressure Recordings.

INTRODUCTION: Prior studies conducted in peritoneal dialysis (PD) patients in the late 1990s provided considerably variable estimates of the prevalence and control of hypertension. The present study aimed to investigate the current state of hypertension management in this high-risk population. METHODS: In 140 stable PD patients, we performed standardized automated office blood pressure (BP) measurements and 24-h ambulatory BP monitoring (ABPM) using the Mobil-O-Graph device (IEM, Germany). Office and ambulatory hypertension was diagnosed in patients with office BP ≥140/90 mm Hg and 24-h BP ≥130/80 mm Hg, respectively. Patients treated with ≥1 BP-lowering medications were also classified as hypertensives. RESULTS: The prevalence of office and ambulatory hypertension was 92.9% and 95%, respectively. In all, 92.1% of patients were being treated with an average of 2.4 BP-lowering medications daily. Adequate BP control was achieved in 52.3% and 38.3% of hypertensives by office BP and ABPM, respectively. The agreement between these 2 techniques in the identification of patients with BP levels above the diagnostic thresholds of hypertension was moderate (k-statistic: 0.524). In all, 5% of patients were normotensives with both techniques, 31.4% had controlled hypertension, 5% had white-coat hypertension, 19.3% had masked hypertension, and 39.3% had sustained hypertension. Isolated nocturnal hypertension was detected in 23.6% of patients, whereas no patient had isolated daytime hypertension. CONCLUSION: Among PD patients, hypertension is highly prevalent and remains often inadequately controlled. The use of ABPM enables the better classification of severity of hypertension and identification of isolated nocturnal hypertension, which is a common BP phenotype in the PD population.

Prevalence, recurrence and seasonal variation of hyperkalemia among patients on hemodialysis.

PURPOSE: Observational studies have shown that among patients on hemodialysis, hyperkalemia is strongly associated with excess risk for cardiovascular-related hospitalizations and sudden cardiac death. However, the actual burden of hyperkalemia, the rates of its recurrence and seasonality in its variation still remain unclear. METHODS: Between June 2020 and May 2021, 1786 mid-week pre-dialysis serum potassium (sK) measurements were retrospectively recorded from 149 patients receiving thrice-weekly hemodialysis in a single-center in Thessaloniki, Greece. The prevalence, recurrence and seasonal variation of hyperkalemia were assessed using three pre-specified sK thresholds (≥ 5.1, ≥ 5.5 and ≥ 6.0 mmol/L). RESULTS: At baseline, 60.4%, 42.2% and 13.4% of patients had sK levels ≥ 5.1, ≥ 5.5 and ≥ 6.0 mmol/L, respectively. At any time-point during follow-up, 85.2%, 69.8% and 38.9% of patients experienced at least one hyperkalemic event ≥ 5.1, ≥ 5.5 and ≥ 6.0 mmol/L, respectively. Of the 104 patients experiencing an initial sK elevation ≥ 5.5 mmol/L, hyperkalemia at the same threshold reoccurred in 60.6% at month 1, in 47.1% at month 2 and in 46.1% at month 3 of follow-up. Seasonal variation was also observed, with the prevalence of hyperkalemia to be significantly higher in summer. Shorter delivered hemodialysis < 4 h/session (OR: 2.568; 95% CI 1.045-6.313) and the use of a high dialysate K concentration (OR: 14.646; 95% CI 2.727-78.647) were the 2 factors that were independently associated with hyperkalemia. CONCLUSION: The present study shows that among hemodialysis patients, the rates of hyperkalemia prevalence and recurrence are very high, reflecting the large unmet need to identify more effective potassium-lowering therapeutic interventions in this high-risk population.

A comparative analysis of ambulatory BP profile and arterial stiffness between CAPD and APD.

Prior studies have associated automated peritoneal dialysis (APD) with less effective volume and blood pressure (BP) control as compared with continuous ambulatory peritoneal dialysis (CAPD). Our study aimed to compare the volume status, ambulatory BP profile and severity of arterial stiffness between patients treated with CAPD versus APD. In a case-control design, 28 CAPD patients were matched in 1:1 ratio with 28 controls receiving APD for age, gender and diabetic status. Body composition was assessed with the method of bioimpendence spectroscopy. Twenty-four hours ambulatory BP monitoring with the Mobil-O-Graph device (IEM, Germany) was performed to determine peripheral and central hemodynamic parameters, heart rate-adjusted augmentation index (AIx75) and pulse wave velocity (PWV). Standardized office BP, antihypertensive medication use and extracellular-to-total body water ratio did not differ between CAPD and APD groups. Twenty-four hours brachial systolic BP (129.0 ± 17.3 vs. 128.1 ± 14.2 mmHg, P = 0.83) and 24-h aortic systolic BP (116.9 ± 16.4 vs. 116.4 ± 11.6 mmHg, P = 0.87) were similar in patients treated with CAPD versus APD. Similarly, there was no significant difference between PD modalities in severity of arterial stiffness, as assessed with 24-h AIx75 (24.8 ± 8.9 vs. 22.5 ± 9.1, P = 0.36) and 24-h PWV (9.1 ± 2.4 vs. 8.8 ± 2.1 m/s, P = 0.61). The present study suggests that there is no difference in peripheral and central hemodynamic parameters as well as in the severity of arterial stiffness between CAPD and APD. However, these observations should be interpreted within the context of clinical characteristics of patients included in this case-control study. The comparative effectiveness of these 2 PD modalities warrants further investigation in larger longitudinal studies.

Age dependence of brachial cuff-based ambulatory PWV in end-stage kidney disease patients undergoing long-term peritoneal dialysis.

BACKGROUND: The newly introduced device Mobil-O-Graph (IEM, Stolberg, Germany) combines brachial cuff oscillometry and pulse wave analysis, enabling the determination of pulse wave velocity (PWV) via complex mathematic algorithms during 24-h ambulatory blood pressure monitoring (ABPM). However, the determinants of oscillometric PWV in the end-stage kidney disease (ESKD) population remain poorly understood. METHODS: In this study, 81 ESKD patients undergoing long-term peritoneal dialysis underwent 24-h ABPM with the Mobil-O-Graph device. The association of 24-h oscillometric PWV with several demographic, clinical and haemodynamic parameters was explored using linear regression analysis. RESULTS: In univariate analysis, among 21 risk factors, 24-h PWV exhibited a positive relationship with age, body mass index, overhydration assessed via bioimpedance spectroscopy, diabetic status, history of dyslipidaemia and coronary heart disease, and it had a negative relationship with female sex and 24-h heart rate. In stepwise multivariate analysis, age (ß: 0.883), 24-h systolic blood pressure (BP) (ß: 0.217) and 24-h heart rate (ß: -0.083) were the only three factors that remained as independent determinants of 24-h PWV (adjusted R 2 = 0.929). These associations were not modified when all 21 risk factors were analysed conjointly or when the model included only variables shown to be significant in univariate comparisons. CONCLUSION: The present study shows that age together with simultaneously assessed oscillometric BP and heart rate are the major determinants of Mobil-O-Graph-derived PWV, explaining >90% of the total variation of this marker. This age dependence of oscillometric PWV limits the validity of this marker to detect the premature vascular ageing, a unique characteristic of vascular remodelling in ESKD.

The Relation of Clinic and Ambulatory BP with the Risk of Cardiovascular Events and All-Cause Mortality among Patients on Peritoneal Dialysis.

Large observational studies showed a U-shaped association of clinic blood pressure (BP) with mortality among patients undergoing peritoneal dialysis (PD). Whether ambulatory BP provides a more direct risk signal in this population remains unknown. In a prospective cohort of 108 PD patients, standardized clinic BP was recorded at baseline with the validated device HEM-705 (Omron, Healthcare, Bannockburn, IL, USA) and 24-h ambulatory BP monitoring was performed using the Mobil-O-Graph monitor (IEM, Stolberg, Germany). Over a median follow-up of 16 months (interquartile range: 19 months), 47.2% of the overall population reached the composite outcome of non-fatal myocardial infarction, non-fatal stroke, or all-cause death. In Cox-regression analysis, systolic but not diastolic BP was prognostically informative. Compared with the reference quartile 1 of 24-h systolic BP (SBP), the multivariate-adjusted hazard ratio for the composite outcome was 1.098 (95% confidence interval (CI): 0.434-2.777) in quartile 2, 1.004 (95% CI: 0.382-2.235) in quartile 3 and 2.449 (95% CI: 1.156-5.190) in quartile 4. In contrast, no such association was observed between increasing quartiles of clinic SBP and composite outcome. The present study shows that among PD patients, increasing ambulatory SBP is independently associated with higher risk of adverse cardiovascular events and mortality, providing superior prognostic information than standardized clinic SBP.