Hypertensive Emergency During Dialysis: A Paradoxical Physiologic Response.

Most end-stage renal disease patients experience a reduction in blood pressure during their hemodialysis session compared to predialysis. Surprisingly, a small subset of patients will experience an unusual physiological response to dialysis that results in a paradoxical increase in blood pressure. We discuss a case that involved an exaggerated elevation in blood pressure, ultimately requiring immediate cessation of dialysis and admission to the intensive care unit for intravenous treatment of a hypertensive emergency. This case serves as a framework to introduce the infrequently discussed concept of intradialytic hypertension. The underlying pathogenesis is poorly understood with multiple theoretical etiologies including activation of the renin-angiotensin-aldosterone system, imbalances in circulating levels of endothelium-derived mediators, clearance of antihypertensive medications, increased cardiac output, and changes in arterial thickness. It is important to be cognizant of this phenomenon as emerging evidence suggests that patients with any elevation in blood pressure during hemodialysis have increased rates of both short-term and long-term mortality.

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

BACKGROUND AND HYPOTHESIS: Intradialytic-hypertension (IDH) is associated with increased risk for cardiovascular events and mortality. Patients with IDH exhibit higher 48-h blood pressure (BP) levels than patients without this condition. Volume and sodium excess are considered a major factor contributing in the development of this phenomenon. This study evaluated the effect of low (137mEq/L) compared to standard (140mEq/L) dialysate sodium concentration on 48-h BP in patients with IDH. METHODS: In this randomized, single-blind, crossover study, 29 patients with IDH underwent 4 hemodialysis sessions with low (137mEq/L) followed by 4 sessions with standard (140mEq/L) dialysate sodium or vice-versa. Mean 48-h BP, pre-/post-dialysis and intradialytic BP, pre-dialysis weight, interdialytic weight gain (IDWG) and lung ultrasound B-lines were assessed. RESULTS: Mean 48-h SBP/DBP were significantly lower with low compared to standard dialysate sodium concentration (137.6±17.0/81.4±13.7mmHg with low vs 142.9±14.5/84.0±13.9mmHg with standard dialysate sodium, p=0.005/p=0.007 respectively); SBP/DBP levels were also significantly lower during the 44-h and different 24-h periods. Low dialysate sodium significantly reduced post-dialysis (SBP/DBP: 150.3±22.3/91.2±15.1mmHg with low vs 166.6±17.3/94.5±14.9mmHg with standard dialysate sodium, p<0.001/p=0.134 respectively) and intradialytic (141.4±18.0/85.0±13.4mmHg with low vs 147.5±13.6/88.1±12.5mmHg with standard dialysate sodium, p=0.034/p=0.013, respectively) BP compared with standard dialysate sodium. Pre-dialysis weight, IDWG and pre-dialysis B-lines were also significantly decreased with low dialysate sodium. CONCLUSIONS: Low dialysate sodium concentration significantly reduced 48-h ambulatory BP compared with standard dialysate sodium in patients with IDH. These findings support low dialysate sodium as a major non-pharmacologic approach for BP management in patients with IDH.Registered at ClinicalTrials.gov with study number NCT05430438.

Beta-blocker efficacy for intra- and interdialytic hypertension patients: a systematic review and meta-analysis.

PURPOSE: Intradialytic hypertension affects 5-15% of hemodialysis patients, yet relevant studies are relatively scarce. It is also associated with higher interdialytic blood pressure. Beta-blockers can be preferred as antihypertensive drugs due to their superior blood pressure control, decreased risk of cardiovascular events, improved endothelial cell function, and decreased noradrenaline levels. Through this study, beta-blocker antihypertensive effects in intra- and interdialytic hypertension were analyzed. METHODS: Systematic review and meta-analysis were performed following PRISMA guidelines. We registered our PROSPERO protocol (Registration ID: CRD42023446184) and included relevant full-text clinical trials or RCTs from 2008 to 2023 with predetermined keywords and criteria from multiple databases including PUBMED, COCHRANE, SCOPUS, and citation searching. Seven eligible articles were included in this review study. RESULTS: Four studies with 82 participants for intradialytic hypertension evaluation were included. Meta-analysis showed a decrease in SBP in intradialytic hypertensive patients after beta-blocker intervention, with a significant estimated mean difference of - 15.19 mmHg (P < 0.00001; 95% CI - 19.47 to - 10.91). Supporting previous data, SBP remains constant between pre- and post-dialysis with beta-blocker therapy, with an insignificant estimated mean difference of - 2.72 mmHg (P = 0.29; 95% CI - 7.80 to 2.36). Whereas five studies with 142 participants were included for interdialytic hypertension evaluation. Meta-analysis shows a significant decrease in SBP before to after therapy, with an estimated mean difference of - 10.92 (P < 0.0001; 95% CI - 16.33 to - 5.51). CONCLUSION: Beta-blocker treatment resulted in significant reductions in post-hemodialysis systolic blood pressure among intra- and interdialytic hypertensive patients.

Randomized Trial on the Effects of Dialysate Potassium Concentration on Intradialytic Hypertension.

Introduction: Intradialytic hypertension is not an uncommon condition during chronic hemodialysis. It is associated with unfavorable cardiovascular outcomes, including hospitalization and mortality. Several small studies have demonstrated the contradictory effects of different dialysate potassium concentrations on intradialytic blood pressure. This study is a randomized crossover trial aiming to evaluate the effects of different dialysate potassium concentrations on intradialytic hypertension. Methods: A 24-week, 2-treatment, 4-sequence, multicenter, double-blinded, randomized, crossover study was conducted at Maharaj Nakorn Chiang Mai Hospital and Lampang Hospital in Thailand among stable patients receiving chronic hemodialysis who experienced intradialytic hypertension >30% of their sessions over the past 3 months. Each participant was randomly assigned to 1 of 4 treatment sequences. During each intervention period, patients were dialyzed with dialysate potassium of either 2 mmol/l (D-K2) or 3 mmol/l (D-K3) for 4 weeks according to their preassigned sequence, separated by a 2-week washout period. The primary outcome was the incidence of intradialytic hypertension. Results: Forty eligible patients were recruited. The mean age was 61.4 ± 14.2 years and the mean systolic blood pressure (SBP) was 146.6 ± 11.2 mm Hg. Of the 40 patients, 95.5% had hypertension and their average number of antihypertensive drugs was 2.8 ± 1.9. A total of 1380 dialysis sessions were included in the analysis (695 sessions for D-K2 and 685 sessions for D-K3). The incidence of intradialytic hypertension was not significantly different between different dialysate potassium concentrations (D-K2 54.7% vs. D-K3 53.1%, P = 0.788). The changes in SBP, diastolic blood pressure (DBP), and mean arterial pressure (MAP) were not different between the 2 dialysate potassium groups. Conclusion: Dialysate potassium concentration of 2 or 3 mmol/l did not affect the incidence of intradialytic hypertension in patients receiving chronic hemodialysis who frequently developed intradialytic hypertension.

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

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

Epidemiology, Pathophysiology, and Clinical Perspectives of Intradialytic Hypertension.

BACKGROUND: Individuals with end-stage renal disease on chronic hemodialysis (HD) may encounter numerous HD-associated complications, including intradialytic hypertension (IDHYPER). Although blood pressure (BP) follows a predictable course in the post-HD period, BP levels during the session may vary across the individuals. Typically, a decline in BP is noted during HD, but a significant proportion of patients exhibit a paradoxical elevation. SUMMARY: Several studies have been conducted to understand the complexity of IDHYPER, but much remains to be elucidated in the future. This review article aimed to present the current evidence regarding the proposed definitions, the pathophysiologic background, the extent and clinical implications of IDHYPER, as well as the possible therapeutic options that have emerged from clinical studies. KEY MESSAGES: IDHYPER is noted in approximately 15% of individuals undergoing HD. Several definitions have been proposed, with a systolic BP rise >10 mm Hg from pre- to post-dialysis in the hypertensive range in at least four out of six consecutive HD treatments being suggested by the latest Kidney Disease: Improving Global Outcomes. Concerning its pathophysiology, extracellular fluid overload is a crucial determinant, with endothelial dysfunction, sympathetic nervous system overdrive, renin-angiotensin-aldosterone system activation, and electrolyte alterations being important contributors. Although its association with ambulatory BP in the interdialytic period is controversial, IDHYPER is associated with adverse cardiovascular events and mortality. Moving to its management, the antihypertensive drugs of choice should ideally be nondialyzable with proven cardiovascular and mortality benefits. Finally, rigorous clinical and objective assessment of extracellular fluid volume is essential. Volume-overloaded patients should be instructed about the importance of sodium restriction, while physicians ought to alter HD settings toward a greater dry weight reduction. The use of a low-sodium dialysate and isothermic HD could also be considered on a case-by-case basis since no randomized evidence is currently available.

Vascular Access in Hemodialysis: Peculiarities in a Low-Income Setting, Pattern, Prevalence and Relationship with Intradialysis Events and Dialysis Dose.

OBJECTIVES: Dialysis vascular access has remained a major determinant of intra and inter-dialytic events and the dialysis dose, and this impacts the quality of life, morbidity and mortality of dialysis patients. Assessing the different access types would help minimize peri-dialytic events and improve outcome. METHODS: This was a retrospective, age and sex-matched, comparative study that assessed dialysis sessions with tunneled dialysis catheters (TDCs) with arteriovenous fistula (AVF). RESULTS: Two hundred and four participants with 1062 sessions were involved. The male participants had 66.7% of all sessions, 60.6% of sessions with TDCs and 87.3% of sessions with AVF, P=0.001. The elderly constituted 23.5% of all participants but 37.7% of sessions with AVF, P=0.04. The percentage of the health-insured was more in sessions with AVF compared to the study population, P<0.001. Diabetics were more likely to use the TDCs, P=0.06. Participants using AVF were more likely to receive full dialysis and erythropoietin treatment, P<0.001. Intradialytic hypotension and dialysis termination were commoner with AVF than TDCs, P=0.03 and P=0.04 respectively. The dialysis dose was higher with AVF than TDCs, P=0.02. Predictors of AVF as dialysis access were male gender, advancing age, health insurance and full treatment compliance. CONCLUSION: There is predominance of venous catheters in our dialysis population. The AVF gave better BP control, fluid and solute clearance, and dialysis dose, and was commoner with males, the health insured and older participants. Intradialytic hypotension was commoner with AVF as IDHT was commoner with TDCs.

OBJECTIFS: L'accès vasculaire à la dialyse reste un déterminant majeur des événements intra et inter-dialytiques et de la dose de dialyse, ce qui a un impact sur la qualité de vie, la morbidité et lamortalité des dialysés. L'évaluation des différents types d'accès permettrait de minimiser les événements péridialytiques et d'améliorer les résultats. MÉTHODES: Il s'agit d'une étude comparative rétrospective, appariée selon l'âge et le sexe, qui a évalué les séances de dialyse avec des cathéters de dialyse tunnellisés (CDT) et des fistules artérioveineuses (FAV). RÉSULTATS: Deux cent quatre participants ont participé à 1 062 séances. Les hommes représentaient 66,7 % de toutes les séances, 60,6 % des séances avec CDT et 87,3 % des séances avec FAV, P=0,001. Les personnes âgées représentaient 23,5 % de l'ensemble des participants, mais 37,7 % des séances avec FVA, P=0,04. Le pourcentage d'assurés sociaux était plus élevé dans les sessions avec AVF que dans la population étudiée, P<0.001. Les diabétiques étaient plus susceptibles d'utiliser les CDT, P=0,06. Les participants utilisant la FVA étaient plus susceptibles de recevoir une dialyse complète et un traitement à l'érythropoïétine, P<0,001. L'hypotension intradialytique et l'arrêt de la dialyse étaient plus fréquents avec l'AVF qu'avec les CDT, P=0,03 et P=0,04. La dose de dialyse était plus élevée en cas de FVA qu'en cas de CDT, P=0,02. Les facteurs prédictifs de l'utilisation de la FVA comme accès à la dialyse étaient le sexe masculin, l'âge avancé, l'assurance maladie et l'observance totale du traitement. CONCLUSION: Il y a une prédominance des cathéters veineux dans notre population de dialysés. Le FVA permet un meilleur contrôle de la PA, de la clairance des fluides et des solutés et de la dose de dialyse, et il est plus fréquent chez les hommes, les assurés sociaux et les participants plus âgés. L'hypotension intradialytique était plus fréquente avec le FVA que l'IDHT était plus fréquente avec les CDT. Mots-clés: Cathéters veineux centraux, fistule artério-veineuse, veine jugulaire interne tunnellisée.

Associations of Iron Sucrose and Intradialytic Blood Pressure.

RATIONALE & OBJECTIVE: Intradialytic hypotension and intradialytic hypertension are associated with morbidity and mortality in hemodialysis (HD). Many factors can contribute to intra-HD blood pressure (BP) changes, such as drugs with vasoactive properties that can destabilize an already tenuous BP. Intravenous iron sucrose is commonly administered to correct iron deficiency; however, its reported associations with altered hemodynamics have not been consistent. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 950 outpatients receiving maintenance HD. EXPOSURE: Iron sucrose administered during HD. OUTCOME: Intradialytic hypotension, intradialytic hypertension, systolic blood pressure parameters. ANALYTICAL APPROACH: Unadjusted and adjusted Poisson and linear repeated measures regression models. RESULTS: The mean age of patients included in the study was 53±22 years, 43% were female, and 38% were Black. Mean pre-HD SBP was 152±26 (SD) mm Hg. At baseline, the patients who received higher doses of iron sucrose tended to have diabetes, have longer HD sessions, and have a higher frequency of erythropoiesis-stimulating agent use, compared with those who did not receive iron sucrose. In adjusted models, higher doses of iron sucrose were associated with an 11% lower rate of intradialytic hypotension (incidence rate ratio [IRR] for iron sucrose≥100mg vs 0 mg, 0.89 [95% CI, 0.85-0.94]). In adjusted analyses, the administration of higher doses of iron sucrose during HD was associated with intradialytic hypertension (IRR for iron sucrose≥100mg vs 0 mg, 1.07 [95% CI, 1.04-1.10]). LIMITATIONS: Nonavailability of the precise iron sucrose formulation (volume), laboratory data for each HD session, and outpatient medications. Objective measures of volume status, home medications, and symptom data were not recorded in this study. CONCLUSIONS: We observed an independent association of intravenous iron sucrose administration during HD with a lower risk of intradialytic hypotension and higher risk of intradialytic hypertension. Future studies to better understand the mechanisms underlying these associations are warranted. PLAIN-LANGUAGE SUMMARY: Intradialytic hypotension and intradialytic hypertension are common among patients on hemodialysis, and they are associated with morbidity and mortality. Although many factors may contribute to these risks, medications administered during hemodialysis play an important role. We studied the significance of the intravenous iron sucrose used to treat iron deficiency and the impact it may have on blood pressure during dialysis. In our study of 950 outpatient hemodialysis patients, we observed that administration of iron sucrose was associated with higher systolic blood pressure (during and after hemodialysis sessions) as well as a lower risk of intradialytic hypotension. We also observed that higher doses of iron sucrose are associated with the development of intradialytic hypertension.

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

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

Intradialytic hypertension: epidemiology and pathophysiology of a silent killer.

The term intradialytic hypertension (IDH) describes a paradoxical rise in blood pressure (BP) during or immediately after the hemodialysis session. Although it was formerly considered a phenomenon without clinical implications, current evidence suggests that IDH may affect up to 15% of hemodialysis patients and exhibit independent associations with future cardiovascular events and all-cause mortality. Furthermore, during the last decade, several studies have tried to elucidate the complex pathophysiological mechanisms responsible for this phenomenon. Volume overload, intradialytic sodium gain, overactivity of the sympathetic-nervous-system and renin-angiotensin-aldosterone system, endothelial dysfunction and dialysis-related electrolyte disturbances have been proposed to be involved in the pathogenesis of the BP increase during hemodialysis. This review attempts to summarize existing evidence on the epidemiology, pathophysiology and clinical characteristics of the distinct phenomenon of IDH.

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

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

Frequency of Intradialytic Hypertension Using Kidney Disease: Improving Global Outcomes (KDIGO) Suggested Definition in a Single Hemodialysis Centre in Pakistan.

OBJECTIVES:  To estimate the frequency of intradialytic hypertension (IDH) in our centre as per the definition suggested by Kidney Disease: Improving Global Outcomes (KDIGO). METHODS:  A cross-sectional study was conducted at the dialysis department of The Kidney Centre Post Graduate Training Institute (PGTI) Karachi, Pakistan from August 2021 to October 2021 among 263 end-stage kidney disease (ESKD) patients on maintenance hemodialysis (MHD) aged ≥ 18 years of both genders. The study outcome was the frequency of IDH as per the latest KDIGO suggested definition i.e., systolic blood pressure (SBP) rise of > 10 mm Hg from pre- to post-dialysis within the hypertensive range in at least four out of six consecutive dialysis treatments. Frequencies (%) and mean (±SD) were calculated for categorical and continuous variables respectively, using SPSS version 21 (IBM Corp., Armonk, NY, USA). RESULTS:  Among 263 patients, the mean age was 51.02 (±14.1) years and 56.3% were males. Around 30.8% of patients were dialysis-dependent for 1.1 to three years. The most common comorbidity was hypertension (88.6%). Standard dialysate calcium of 3mEq/l was received by 91.6% of study participants. About 78.7% of patients were using antihypertensive(s), out of which 85.5% were compliant and 37.6% were using a single antihypertensive. The most common antihypertensive in use was beta-blockers (78.3%). Around 16% of patients were found to have IDH. Age of the patients was significantly associated with IDH (p=0.038). The majority of the patients with IDH were those who were taking anti-hypertension medications as compared to the patients who were not taking them (p <0.004). Interdialytic weight gain was not a significant predictor for IDH. CONCLUSION:  The frequency of IDH was 16% according to the latest suggested KDIGO definition. This is much lower than regional and global estimates according to earlier definitions. There is a dire need to establish a standardized definition of IDH in guidelines to diagnose, manage and compare data. Also, the association of IDH with fluid overload is not found in our study which emphasizes the need to evaluate other causative factors.

The effects of extracellular volume and intradialytic peripheral resistance changes on ambulatory blood pressure in hemodialysis patients with and without recurrent intradialytic hypertension.

BACKGROUND: Hypertension and extracellular volume (ECV) overload are interrelated mortality risk factors in hemodialysis (HD) patients, but confounding related to changes in ECV and vasoconstriction during and between treatments obfuscate their relationship. We sought to clarify independent contributions of post-HD ECV and intradialytic changes in vasoconstriction on ambulatory blood pressure (BP) in patients with and without recurrent intradialytic hypertension (IH). METHODS: In this prospective observational study, we obtained measurements of pre- and post-HD ECV with bioimpedance spectroscopy (BIS), pre- and post-HD total peripheral resistance index and 44-h ambulatory BP. Linear regression determined associations between post-HD ECV/weight and intradialytic change in total peripheral resistance index (TPRI) with interdialytic BP and slope. RESULTS: In fully-adjusted models for participants with complete data, post-HD ECV/weight associated with mean ambulatory BP (ß = 133, P = 0.01; n = 52) and ambulatory BP slope (ß = -4.28, P = 0.03; n = 42). ECV/weight was associated with mean ambulatory BP in those with recurrent IH (ß = 314, P = 0.0005; n = 16) and with ambulatory BP slope in those without recurrent IH (ß = -4.56, P = 0.04; n = 28). Interdialytic weight gain percentage and intradialytic TPRI change were not associated with ambulatory BP or slope in any analyses. CONCLUSION: Ambulatory BP in HD patients is more strongly associated with post-HD ECV assessed with BIS than with intradialytic TPRI changes or interdialytic ECV increases. These findings highlight the essential role of recognizing and managing chronic ECV overload to improve ambulatory BP in HD patients, particularly so for those with IH.

Effect of low dialysate sodium in the management of intradialytic hypertension in maintenance hemodialysis patients: A single-center Indian experience.

BACKGROUND: High dialysate sodium is a significant contributor to intradialytic hypertension (IDH) in maintenance hemodialysis patients. In this study, we aimed to study the effect of low dialysate sodium on IDH in Indian hemodialysis patients. MATERIALS AND METHODS: Fifty patients on maintenance hemodialysis for atleast 3 months with episodes of IDH were enrolled in this study. The study was performed in two different stages. In the first phase, patients were dialyzed with standard dialysate sodium (140 mEq/L) for eight consecutive sessions and in the second phase, they were dialyzed with low sodium dialysate (136 mEq/L) for eight consecutive sessions. Differences in pre, intradialytic, and post-HD blood pressure, interdialytic weight gain, mean serum sodium, intradialytic adverse events, and number of IDH episodes requiring intervention between the two phases were assessed. RESULTS: The mean age of the study population was 52 years (36 males,14 females). The mean post-HD systolic and diastolic BP was 163.26 ± 9.58 mmHg and 88.60 ± 5.27 mmHg in the standard dialysate phase and 142.38 ± 14.09 mmHg and 84.58 ± 4.276 mmHg, respectively, in the low dialysate phase (p < 0.01). Interdialytic weight gain was 3.34 ± 0.9 and 3.11 ± 0.86 in the standard and low sodium dialysate phases, respectively (p = 0.19).The mean pre-HD plasma sodium level was 138.48 ± 3.69 and 135.80 ± 1.35 mEq/dl, respectively, in standard and low dialysate phases (p = 0.01). There was significant reduction in number of IDH episodes requiring intervention. There was no difference in hypotensive episodes, adverse events between the two phases. CONCLUSION: In patients with intradialytic hypertension, low dialysate sodium significantly reduces the post-HD blood pressure and intradialytic hypertensive episodes, when compared with standard sodium dialysate.

Association of pre-pro-endothelin gene polymorphism and serum endothelin-1 with intradialytic hypertension in an Egyptian population.

BACKGROUND: Intradialytic hypertension (IDH) is a major problem of hemodialysis and it is a multifactorial disorder and need early identification and management. AIM: Evaluate the serum concentration of endothelin-1 in patients with IDH and healthy control and the impact of pre-pro-endothelin gene polymorphism on level of endothelin-1 and susceptibility to IDH in Egyptian population. METHODS: The patient groups divided into group I, End stage renal disease (ESRD) on chronic hemodialysis with IDH (112); group II, ESRD on chronic hemodialysis without IDH (112); group III, healthy control (112). All undergone to full history, clinical examination, routine laboratory investigations, echocardiography, serum ET-1 level by ELISA and A(8002)G polymorphism detection in pre-pro-endothelin gene by PCR-RFLP. RESULTS: Our results showed significantly higher concentration of Endothelin-1 (ET-1) in both patient groups than healthy control and in group with IDH than cases without IDH (p < 0.001). GG, GA and mutated G allele carry the risk of IDH (OR = 15.94, 13.5, 5.51 respectively p < 0.001). There was association between GG and GA genotypes and higher ET-1 level in both patient groups (p < 0.001) and association between GG and GA genotype and higher mean arterial pressure (MAP), delta MAP (DMAP) and increased left ventricular mass index (LVMI) in both patient groups (p = 0.001, 0.028). CONCLUSION: Pre-pro-endothelin gene polymorphism A(8002)G is an independent risk factor for IDH through changing the level of ET-1 concentration in Egyptian population undergoing chronic hemodialysis.

Lower Levels of Blood Zinc Associated with Intradialytic Hypertension in Maintenance Hemodialysis Patients.

Intradialytic hypertension (iHTN) has been related with an increased risk of mortality, with imbalances in trace elements being frequent in maintenance hemodialysis (MHD) patients. The aim of this study was to analyze the relationships between the levels of blood trace elements and iHTN in MHD patients. A total of 144 MHD patients were enrolled in September, 2019 (66 females; 5616 hemodialysis treatments), with a mean age of 64.33 ± 13.39 years and median vintage of 33.50 (16.25-57.50) months. Patients exhibited an average peridialytic systolic blood pressure (SBP) change of - 4.18 ± 20.22 mm Hg in the next 3 months. Thirty-four (23.6%) patients had persistent iHTN (piHTN). These patients were characterized by older age, higher rate of hypozincemia, and modified Charlson comorbidity score, whereas lower blood zinc and hemoglobin, at the time of their recruitment. No significant difference in the levels of other blood trace elements was observed between groups. A general linear mixed (GLM) model showed that with every mg/L point lower mean blood zinc at baseline, the peridialytic SBP change was increased by 4.524 mm Hg (P < 0.001). Binary logistic model in modulate of the GLM model revealed that the lower level of blood zinc was associated with piHTN (OR = 0.433, 95 % CI 0.295 to 0.637, P < 0.001). Multivariate analysis confirmed both above results. Our study indicated that lower blood zinc was independently associated with piHTN in patients undergoing MHD, but prospective studies with larger population are still needed.

The Effects of Nebivolol and Irbesartan on Ambulatory Aortic Blood Pressure and Arterial Stiffness in Hemodialysis Patients with Intradialytic Hypertension.

BACKGROUND: Intradialytic hypertension occurs in 5-15% of hemodialysis patients and is associated with increased cardiovascular risk, but the responsible mechanisms remain unknown. This study examined the effects of nebivolol and irbesartan on ambulatory central blood pressure (BP), arterial stiffness, and wave-reflection parameters in patients with intradialytic hypertension. METHODS: This is a prespecified analysis of a single-blind, randomized, cross-over study in 38 hemodialysis patients with intradialytic hypertension. Patients were randomized to nebivolol 5 mg followed byirbesartan 150 mg, or vice versa. In a non-randomized manner, the first half of the patients (n = 19) received a single drug dose 1 h prior to dialysis session and the remaining received the drugs for a whole week before the evaluation. Ambulatory central BP, arterial stiffness, and wave-reflection parameters were estimated with Mobil-O-Graph NG device, during a midweek dialysis day. RESULTS: Intake of a single dose of nebivolol or irbesartan resulted in lower postdialysis central systolic BP (c-SBP) (baseline: 140.9 ± 15.4; nebivolol: 130.3 ± 19.5, p = 0.009; irbesartan: 127.3 ± 24.4 mm Hg, p = 0.007). Single-dose nebivolol also produced marginally lower 24-h c-SBP (p = 0.064) and lower 24-h central diastolic BP (c-DBP) (p = 0.029). Weekly administration of both drugs reduced postdialysis c-SBP (baseline: 144.1 ± 15.3; nebivolol: 131.8 ± 14.1, p = 0.014; irbesartan: 126.4 ± 17.8, p = 0.001) and 24-h c-SBP and c-DBP (baseline: 135.5 ± 10.3/91.9 ± 9.2; nebivolol: 126.4 ± 8.4/86.6 ± 7.2, p < 0.001/p = 0.002; irbesartan: 128.7 ± 11.6/87.0 ± 9.4, p = 0.061/p = 0.051 mm Hg). Single-dose intake of both drugs did not affect heart rate-adjusted augmentation index [AIx(75)], but decreased postdialysis pulse wave velocity (PWV). Importantly, weekly administration of both drugs reduced 24-h PWV (baseline: 10.0 ± 2.5; nebivolol: 9.7 ± 2.5, p = 0.012; irbesartan: 9.7 ± 2.7, p = 0.041). In between drug-group comparisons, no significant differences were noted. CONCLUSIONS: This is the first randomized evaluation on the effects of pharmacological interventions on central BP and PWV in patients with intradialytic hypertension. Weekly administration of both nebivolol and irbesartan reduced 24-h central BP and PWV, but not AIx(75).

Intradialytic Hypertension Increases Non-access Related Hospitalization and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND AND AIMS: Intradialytic hypertension, in patients on maintenance hemodialysis, is associated with increased morbidity and mortality. As there is no data available from India, this study was aimed to determine the prevalence and outcome of intradialytic hypertension (IDH) in a tertiary care dialysis centre in India. METHODS: This was a prospective analytical study of 120 patients on hemodialysis. At screening phase, all patients were subjected to fluid optimization and adjustment in the antihypertensive medicines for appropriate control of blood pressure (BP). BP measurements during hemodialysis were recorded. The prevalence of IDH was noted. IDH was defined as increase in systolic BP of >10 mmHg from pre to post hemodialysis or after 2nd hour of dialysis when significant ultrafiltration had occurred, on 3 consecutive sessions. Factors associated with IDH were evaluated and compared with cohort without IDH. The outcome of these patients in terms of morbidity and mortality over a follow-up period of 12 months were recorded. RESULTS: The prevalence of IDH was 21.9%. The baseline demographic parameters of patients in both the groups (with and without IDH) including age, sex, dialysis access, duration of dialysis, and comorbidities were similar. Laboratory parameters were similar except serum potassium and serum phosphorus, which were lower in patients with IDH. Out of all the variables studied, only low serum phosphorus was associated independently with IDH. During follow-up, at 6 months, 19/71 (26%) non-IDH and 12/20 (60%) IDH patients (P = 0.006) and at 12 month, 30/71 (42%) non-IDH patients and 12/20 (60%) IDH patients required admission (P = 0.05). Mortality at 6 months was similar, 5/71 (7%) in non-IDH and 4/20 (20%) in IDH (P = 0.10) patients, but was higher at 12 months, 11/71 (15.5%) in non-IDH and 8/20 (40%) in IDH (P = 0.028). CONCLUSION: Incidence of intradialytic hypertension is high (21.9%) with increased morbidity in terms of hospitalization and increased mortality over a period of one year.

Effect of Isothermic Dialysis on Intradialytic Hypertension.

The primary outcome was incidence of intradialytic hypertension (IDH) during standard and cooler isothermic dialysate temperatures. Two pair of haemodialysis sessions were done at 37°C (SHD) and at isothermic temperature (IHD). All the four dialysis were done on the same time of the day to negate the changes due to circadian variation in body temperature. Axillary and tympanic temperatures were measured before start of the dialysis and dialysis temperature was adjusted as per axillary temperature. Sixty patients were enrolled and completed the study. The mean delivered dialysate temperature in the intervention group was 36.5 ± 0.2 achieving a 0.5 ± 0.2°C between-group separation. The incidence of IDH and intradialytic hypotension while on SHD and IHD were 79/120 (66%) vs 44/120 (37%), odds ratio (OR) 3.3, 95% confidence interval (CI) (1.96-5.65) and 45/120 (38%) vs 14/120 (12%), OR 4.5, 95% CI (2.3-8.7), respectively. The 4 h time averaged mean systolic blood pressure (SBP) at IHD and SHD were 154 ± 1.7 and 157.2 ± 1.1 mmHg, respectively, the mean difference in SBP being -3.4 mmHg to -3.1 mmHg, 95% CI, P < 0.001. The standard deviation, a measure of BP variability was lower at IHD than at SHD (P < 0.001). In a subgroup analysis during IHD there was a significant reduction of both SBP and diastolic BP during the entire duration of dialysis in 35 out of 60 patients (systolic 4 h mean 154.96 ± 2.22 vs 164.32 ± 1.99 mmHg), (diastolic 4 h mean 79.24 ± 0.82 vs 82.54 ± 0.68 mmHg) - (rANOVA for systolic and diastolic <0.001). This phenomenon of cooler dialysis causing reduction of BP was reproduced in the same group of patients when the IHD was repeated another time (systolic 4 h mean 157.95 ± 1.88 vs 160.65 ± 1.47), (diastolic 4 h mean 79.27 ± 0.74 vs 82.03 ± 1.07) rANOVA for systolic and diastolic <0.001. The incidence of IDH can be reduced significantly by reducing the dialysate temperature to patients' body temperature. Hypertension during dialysis is related to heat gain during dialysis.

Nebivolol reduces short-term blood pressure variability more potently than irbesartan in patients with intradialytic hypertension.

Increased blood pressure (BP) variability (BPV) is associated with high cardiovascular risk in hemodialysis. Studies on the effects of antihypertensive drugs on BPV in hemodialysis are scarce. This study examines the effects of nebivolol and irbesartan on short-term BPV in patients with intradialytic hypertension. This randomized-cross-over study included 38 patients (age: 60.4 ± 11.1 years, male: 65.8%) with intradialytic hypertension (intradialytic-SBP increase ≥ 10 mmHg at ≥4 over 6 consecutive sessions). After the baseline evaluation, participants were randomized to nebivolol 5 mg and subsequently irbesartan 150 mg, or vice versa, with a two-week wash-out period before initiation of the second drug. Patients underwent three respective 24 h-ABPM sessions starting before a midweek-session. We calculated the standard deviation (SD), weighted SD (wSD), coefficient of variation (CV), and average real variability (ARV) of BP with validated formulas. The post-hemodialysis and 24 h-SBP and DBP levels were significantly lower after treatment with both drugs. The systolic-BPV indices were marginally lower after nebivolol but not after irbesartan compared to baseline (SD: baseline 15.70 ± 4.69; nebivolol 14.45 ± 3.37, p = 0.090; irbesartan 15.39 ± 3.85, p = 0.706; wSD: 14.62 ± 4.36 vs 13.40 ± 3.07, p = 0.053 vs 14.36 ± 3.47, p = 0.805, respectively). The diastolic-BPV indices decreased with nebivolol and increased with irbesartan, resulting in significant differences between the two drugs (SD: baseline 10.56 ± 2.50; nebivolol 9.75 ± 2.12; irbesartan 10.84 ± 1.98, between-drug p = 0.014; wSD: baseline 9.86 ± 2.12; nebivolol 9.34 ± 2.01; irbesartan 10.25 ± 2.01, between-drug p = 0.029). The diastolic-BPV during intradialytic and day-time periods was marginally lower with nebivolol than with irbesartan. During nighttime, the BPV indices were unchanged with either drug. The short-term BPV was reduced after nebivolol but not after irbesartan treatment in patients with intradialytic hypertension. These findings suggest that sympathetic-overdrive may be a major factor that affects BPV in intradialytic hypertension patients.