Hemodynamic effects of low versus high dialysate bicarbonate concentration in hemodialysis patients.

INTRODUCTION: Hemodialysis treatment using standard dialysate bicarbonate concentrations cause transient metabolic alkalosis possibly associated with hemodynamic instability. The aim of this study was to perform a detailed comparison of high and low dialysate bicarbonate in terms of blood pressure, intradialytic hemodynamic parameters, orthostatic blood pressure, and electrolytes. METHODS: Fifteen hemodialysis patients were examined in a single-blind, randomized, controlled, crossover study. Participants underwent a 4-h hemodialysis session with dialysate bicarbonate concentration of 30 or 38 mmol/L with 1 week between interventions. Blood pressure was monitored throughout hemodialysis, while cardiac output, total peripheral resistance, stroke volume, and central blood volume were assessed with ultrasound dilution technique (Transonic). Orthostatic blood pressure was measured pre- and post-hemodialysis. FINDINGS: With similar ultrafiltration (UF) volume (2.6 L), systolic blood pressure (SBP) tended to decrease more during high dialysate bicarbonate compared to low dialysate bicarbonate; the mean (95% confidence interval) between treatment differences in SBP were: 8 (-4; 20) mmHg (end of hemodialysis) and 7 (0; 15) mmHg (post-hemodialysis). Stroke volume decreased whereas total peripheral resistance increased significantly more during high dialysate bicarbonate compared to low dialysate bicarbonate with mean between treatment differences: Stroke volume: 12 (1; 23) mL; Total peripheral resistance: -2.9 (-5.3; -0.5) mmHg/(L/min). Cardiac output tended to decrease more with high dialysate bicarbonate compared to low dialysate bicarbonate with mean between treatment difference 0.7 (0.0; 1.4) L/min. High dialysate bicarbonate caused alkalosis, hypocalcemia, and lower plasma potassium, whereas patients remained normocalcemic with normal pH during low dialysate bicarbonate. Orthostatic blood pressure response after dialysis did not differ significantly. DISCUSSION: The use of high dialysate bicarbonate compared to low dialysate bicarbonate was associated with hypocalcemia, alkalosis, and a more pronounced hypokalemia. During hemodialysis with UF, a better preservation of blood pressure, stroke volume, and cardiac output may be achieved with low dialysate bicarbonate compared to high dialysate bicarbonate.

Protocol for a randomised controlled trial comparing warfarin with no oral anticoagulation in patients with atrial fibrillation on chronic dialysis: the Danish Warfarin-Dialysis (DANWARD) trial.

INTRODUCTION: Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit. METHODS AND ANALYSIS: The DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0-3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient. ETHICS AND DISSEMINATION: The study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: NCT03862859, EUDRA-CT 2018-000484-86 and CTIS ID 2022-502500-75-00.

Absence of Coronary Artery Disease is a Strong Negative Predictor of Major Adverse Cardiovascular Events in Patients with Chronic Kidney Disease.

Purpose: To investigate the interplay between chronic kidney disease (CKD) and coronary artery disease (CAD) on the incidence of cardiovascular events in patients with suspected chronic coronary syndrome (CCS). Patients and Methods: Patients with suspected CCS who underwent first-time coronary angiography in Western Denmark between 2003 and 2016 were included in this cohort study. Moreover, an age- and sex-matched general population cohort was established. Patients were stratified according to estimated glomerular filtration rate (eGFR). Presence of CAD was defined as ≥1 obstructive stenosis or non-obstructive diffuse disease. Major adverse cardiovascular events (MACE) were defined as a composite of myocardial infarction, ischemic stroke, and cardiac death. Results: A total of 42,611 patients were included with a median follow-up of 7.3 years. Patients without and with CAD had MACE rates per 100 person-years that were 0.52 and 1.67 for eGFR ≥90 mL/min/1.73 m2, 0.68 and 2.09 for eGFR 60-89 mL/min/1.73 m2, 1.27 and 3.85 for eGFR 30-59 mL/min/1.73 m2, and 2.27 and 6.92 for eGFR <30 mL/min/1.73 m2. Comparing to eGFR ≥90 mL/min/1.73 m2, the adjusted incidence rate ratios for MACE were 1.29 (1.10-1.51) for eGFR 60-89 mL/min/1.73 m2, 1.86 (1.49-2.33) for eGFR 30-59 mL/min/1.73 m2, and 3.57 (1.92-6.67) for eGFR <30 mL/min/1.73 m2 in patients without CAD, and 1.11 (1.03-1.20), 1.71 (1.55-1.90), and 2.46 (1.96-3.09) in patients with CAD. The inverse relationship between kidney function and risk of MACE was confirmed when comparing patients with and without CAD to matched individuals in the general population. Conclusion: Absence of CAD is a strong negative predictor of major adverse cardiovascular events in patients with CKD.

Estimated Pulse Wave Velocity Is Associated With All-Cause Mortality During 8.5 Years Follow-up in Patients Undergoing Elective Coronary Angiography.

Background Estimated pulse wave velocity (ePWV) calculated by equations using age and blood pressure has been suggested as a new marker of mortality and cardiovascular risk. However, the prognostic potential of ePWV during long-term follow-up in patients with symptoms of stable angina remains unknown. Methods and Results In this study, ePWV was calculated in 25 066 patients without diabetes, previous myocardial infarction (MI), stroke, heart failure, or valvular disease (mean age 63.7±10.5 years, 58% male) with stable angina pectoris undergoing elective coronary angiography during 2003 to 2016. Multivariable Cox models were used to assess the association with incident all-cause mortality, MI, and stroke. Discrimination was assessed using Harrell´s C-index. During a median follow-up period of 8.5 years (interquartile range 5.5-11.3 years), 779 strokes, 1233 MIs, and 4112 deaths were recorded. ePWV was associated with all-cause mortality (hazard ratio [HR] per 1 m/s, 1.13; 95% CI, 1.05-1.21) and MI (HR per 1 m/s 1.23, 95% CI, 1.09-1.39) after adjusting for age, systolic blood pressure, body mass index, smoking, estimated glomerular filtration rate, Charlson Comorbidity Index score, antihypertensive treatment, statins, aspirin, and number of diseased coronary arteries. Compared with traditional risk factors, the adjusted model with ePWV was associated with a minor but likely not clinically relevant increase in discrimination for mortality, 76.63% with ePWV versus 76.56% without ePWV, P<0.05. Conclusions In patients with stable angina pectoris, ePWV was associated with all-cause mortality and MI beyond traditional risk factors. However, the added prediction of mortality was not improved to a clinically relevant extent.

The use of non-vitamin K oral anticoagulants in dialysis patients-A systematic review.

Non-vitamin K oral anticoagulants (NOACs) are used for prevention of thromboembolic events, but their use in dialysis patients is debatable. This study investigated the available evidence for the use of NOACs in dialysis patients. Online databases were systematically searched for eligible studies including pharmacokinetic (PK) studies, cohort studies, and randomized control trials (RCTs) comparing NOAC with vitamin K antagonist (VKA) or no anticoagulant treatment. Newcastle Ottawa Scale and Cochrane Risk of bias tool were used for quality assessment. Twenty studies were identified (nine PK studies, two RCTs, and nine cohort studies). Most of the studies investigated apixaban or rivaroxaban. In dialysis patients, less accumulation was reported with apixaban and rivaroxaban compared to dabigatran and edoxaban. PK studies indicate that high dose apixaban or rivaroxaban should be avoided. The two RCTs (rivaroxaban/apixaban vs. VKA) were small and underpowered regarding stroke and bleeding outcomes. Most cohort studies found apixaban superior to VKA, whereas comparison of rivaroxaban with VKA yielded conflicting results. Cohort studies comparing apixaban high dose (5 mg) with low dose (2.5 mg) twice daily suggest a lower risk of stroke with high dose but also a higher risk of bleeding with high dose. Apixaban versus no anticoagulation was compared in one cohort study and did not lower the risk of stroke compared with non-treated regardless of apixaban dosage. Widespread use of NOACs in dialysis patients is limited by adequately sized RCTs. Available evidence suggests a potential for use of apixaban and rivaroxaban in reduced dose.

Can patiromer allow for intensified renin-angiotensin-aldosterone system blockade with losartan and spironolactone leading to decreased albuminuria in patients with chronic kidney disease, albuminuria and hyperkalaemia? An open-label randomised controlled trial: MorphCKD.

INTRODUCTION: Chronic kidney disease (CKD) is associated with significantly increased morbidity and mortality. No specific treatment of the underlying condition is available for the majority of patients, but ACE-inhibitors (ACE-I) and angiotensin II-receptor blockers (ARB) slows progression in albuminuric CKD. Adding a mineralocorticoid receptor-antagonist (MRA) like spironolactone has an additive effect. However, renin-angiotensin-aldosterone system (RAAS)-blockade increases the risk of hyperkalaemia which is exacerbated by the presence of CKD. Thus, hyperkalaemia may prevent optimal use of RAAS-blockade in some patients.This project hypothesises that adding a potassium binder (patiromer) allows for improved RAAS-blockade including the use of MRA, thereby reducing albuminuria in patients with albuminuric CKD where full treatment is limited by hyperkalaemia.If successful, the study may lead to improved treatment of this subgroup of patients with CKD. Furthermore, the study will examine the feasibility of potassium binders in patients with CKD. METHODS AND ANALYSIS: An open-label, randomised controlled trial including 140 patients with estimated glomerular filtration rate (eGFR) 25-60 mL/min/1.73 m2, a urinary albumin/creatinine ratio (UACR) >500 mg/g (or 200 mg/g if diabetes mellitus) and a current or two previous plasma-potassium >4.5 mmol/L. Patients who develop hyperkaliaemia >5.5 mmol/L during a run-in phase, in which RAAS-blockade is intesified with the possible addition of spironolactone, are randomised to 12-month treatment with maximal tolerated ACE-I/ARB and spironolactone with or without patiromer.The primary endpoint is the difference in UACR measured at randomisation and 12 months compared between the two groups. Secondary endpoints include CKD progression, episodes of hyperkalaemia, blood pressure, eGFR, markers of cardiovascular disease, diet and quality of life. ETHICS AND DISSEMINATION: This study is approved by The Central Denmark Region Committees on Health Research Ethics (REFNO 1-10-72-110-20) and is registered in the EudraCT database (REFNO 2020-001595-15). Results will be presented in peer-reviewed journals, at meetings and at international conferences.

Effects of Corticosteroid Treatment on Mycophenolic Acid Exposure in Renal Transplant Patients-Results From the SAILOR Study.

Background: Mycophenolic acid (MPA) is a potent immunosuppressive agent used in solid organ transplantation. MPA exhibits large interindividual variation in dose-normalized plasma concentrations but is nevertheless usually prescribed as a fixed dose without use of therapeutic drug monitoring (TDM). Data on the effect of corticosteroid (CS) treatment on MPA concentrations during concomitant tacrolimus treatment remains sparse. Methods: Data is based on TDM of MPA area under the concentration curve (AUC) in 210 renal transplant recipients participating in the prospective, randomized, controlled, multi-center trial (SAILOR) where a steroid-free immunosuppressive regimen with mycophenolate mofetil (MMF) and low-dose tacrolimus was compared with a conventional prednisolone-based treatment regimen. Multilevel mixed-effects linear regression post-hoc analyses of MPA AUC was performed. Results: Median MPA AUC at baseline (within the first 2 weeks post-transplant) in patients taking 2 g MMF daily was 53 mg*h/L (interquartile range: 43-69 mg*h/L, min: 24-max: 117 mg*h/L). Between-patient variation in MPA AUC was up to 5-fold on the same MMF dose. Patients in the steroid-free group had 12.5% lower (95% CI; 3.2-20.9%, p = 0.01) MPA AUC levels at baseline compared to the steroid treated group. During follow-up (14 days-2 years post-transplant) there were no significant differences in MPA AUC between the groups with MPA AUC being 4.2% lower (95% CI: -4.8%-12,5%, p = 0.35) in the steroid-free vs standard treatment group in restricted analysis after multivariate adjustment for tacrolimus trough level, body weight, time after transplantation and MMF dose. MMF dose was positively correlated with MPA AUC (p < 0.001) whereas body weight was negatively correlated with MPA AUC (p < 0.001). MPA AUC was 0.4% (95% CI: 0.2-0.6%, p < 0.001) lower per 1 kg increase in weight. Tacrolimus trough levels had no significant effect on MPA AUC. Conclusion: Immunosuppression with CS during concomitant tacrolimus treatment was shortly after transplantation associated with a significantly higher MPA exposure but the effect was small and not maintained during follow-up. Low body weight was associated with higher MPA exposure, which suggests a potential for weight adjusted MMF dosing.

Vitamin K supplementation and arterial calcification in dialysis: results of the double-blind, randomized, placebo-controlled RenaKvit trial.

BACKGROUND: Arterial calcification is associated with cardiovascular mortality in dialysis patients. Active matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of arterial calcification. Elevated plasma concentrations of inactive MGP, i.e. dephosphorylated-uncarboxylated MGP (dp-ucMGP), are prevalent in dialysis patients. MGP inactivity might contribute to arterial calcification. We investigated whether vitamin K supplementation had an effect on arterial calcification in chronic dialysis patients. METHODS: In a 2-year, double-blind, placebo-controlled intervention trial, 48 dialysis patients were randomized to vitamin K [menaquinone-7 (MK-7), 360 µg daily] or placebo. MK-7 in serum and dp-ucMGP in plasma were used to assess vitamin K status. Carotid-femoral pulse wave velocity (cfPWV) and scores of coronary arterial calcification (CAC) and abdominal aortic calcification (AAC) were used to assess arterial calcification. RESULTS: Thirty-seven participants completed Year 1, and 21 completed Year 2. At Year 2, serum MK-7 was 40-fold higher, and plasma dp-ucMGP 40% lower after vitamin K supplementation compared with placebo {mean dp-ucMGP difference: -1380 pmol/L [95% confidence interval (CI) -2029 to -730]}. There was no significant effect of vitamin K supplementation on cfPWV [mean difference at Year 2: 1.2 m/s (95% CI -0.1 to 2.4)]. CAC Agatston score increased significantly in vitamin K supplemented participants, but was not significantly different from placebo [mean difference at Year 2: 664 (95% CI -554 to 1881)]. AAC scores increased in both groups, significantly so within the placebo group at Year 1, but with no significant between-group differences. CONCLUSIONS: Vitamin K supplementation improved vitamin K status, but did not hinder or modify the progression of arterial calcification in dialysis patients.

The effect of renal denervation on arterial stiffness, central blood pressure and heart rate variability in treatment resistant essential hypertension: a substudy of a randomized sham-controlled double-blinded trial (the ReSET trial).

OBJECTIVES: To investigate, whether renal denervation (RDN) improves arterial stiffness, central blood pressure (C-BP) and heart rate variability (HRV) in patients with treatment resistant hypertension. METHODS: ReSET was a randomized, sham-controlled, double-blinded trial (NCT01459900). RDN was performed by a single experienced operator using the Medtronic unipolar Symplicity FlexTM catheter. C-BP, carotid-femoral pulse wave velocity (PWV), and HRV were obtained at baseline and after six months with the SphygmoCor®-device. RESULTS: Fifty-three patients (77% of the ReSET-cohort) were included in this substudy. The groups were similar at baseline (SHAM/RDN): n = 27/n = 26; 78/65% males; age 59 ± 9/54 ± 8 years (mean ± SD); systolic brachial BP 158 ± 18/154 ± 17 mmHg; systolic 24-hour ambulatory BP 153 ± 14/151 ± 13 mmHg. Changes in PWV (0.1 ± 1.9 (SHAM) vs. -0.6 ± 1.3 (RDN) m/s), systolic C-BP (-2 ± 17 (SHAM) vs. -8 ± 16 (RDN) mmHg), diastolic C-BP (-2 ± 9 (SHAM) vs. -5 ± 9 (RDN) mmHg), and augmentation index (0.7 ± 7.0 (SHAM) vs. 1.0 ± 7.4 (RDN) %) were not significantly different after six months. Changes in HRV-parameters were also not significantly different. Baseline HRV or PWV did not predict BP-response after RDN. CONCLUSIONS: In a sham-controlled setting, there were no significant effects of RDN on arterial stiffness, C-BP and HRV. Thus, the idea of BP-independent effects of RDN on large arteries and cardiac autonomic activity is not supported.

Brain swelling during dialysis: A randomized trial comparing low-flux hemodialysis with pre-dilution hemodiafiltration
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Osmotic changes in plasma are assumed to cause cerebral swelling in hemodialysis patients. We investigated the acute effect of low-flux hemodialysis (HD) (removal of small molecules) and pre-dilution hemodiafiltration (pre-HDF) (additional removal of larger molecules) on cerebral compartment volumes using quantitative magnetic resonance imaging (MRI) in chronic uremic patients. Twelve patients underwent a session of HD and pre-HDF in a randomized crossover study with equal ultrafiltration. MRI was performed immediately before and after dialysis. A linear correlation was found between changes in gray matter and plasma osmolarity (HD: r2 = 0.83; HDF: r2 = 0.73) but not between changes in white matter volume and plasma osmolarity (HD: r2 = 0.02; HDF: r2 = 0.004). Total brain volume increased by 1.8 ± 1.7% (18.7 ± 17.4 mL) (mean ± SD) during HD and 2.0 ± 0.9% (22.3 ± 10.7 mL) during pre-HDF. Gray matter volume increased: HD 3.8% (from -3.6 to 9.7) and pre-HDF 4.2% (from -2.8 to 14.3). White matter volume did not change significantly. Reduction ratio of urea (molecular weight (MW) 0.06 kDa) (HD: 68%; pre-HDF: 69.7%) and ß2-microglobulin (MW 11.7 kDa) (HD: -13.7%; pre-HDF: 67.2%) separated the treatments. This study showed that HD and pre-HDF caused equal acute cerebral swelling of the grey matter. This appeared to be driven by small solute change in plasma interacting linearly with gray matter volume regardless of additional removal of larger molecules or ultrafiltration.
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Short and Long-Term Effects of the Angiotensin II Receptor Blocker Irbesartan on Intradialytic Central Hemodynamics: A Randomized Double-Blind Placebo-Controlled One-Year Intervention Trial (the SAFIR Study).

BACKGROUND AND AIM: Little is known about the tolerability of antihypertensive drugs during hemodialysis treatment. The present study evaluated the use of the angiotensin II receptor blocker (ARB) irbesartan. DESIGN: Randomized, double-blind, placebo-controlled, one-year intervention trial. SETTING AND PARTICIPANTS: Eighty-two hemodialysis patients with urine output >300 mL/day and dialysis vintage <1 year. INTERVENTION: Irbesartan/placebo 300 mg/day for 12 months administered as add-on to antihypertensive treatment using a predialytic systolic blood pressure target of 140 mmHg in all patients. OUTCOMES AND MEASUREMENTS: Cardiac output, stroke volume, central blood volume, total peripheral resistance, mean arterial blood pressure, and frequency of intradialytic hypotension. RESULTS: At baseline, the groups were similar regarding age, comorbidity, blood pressure, antihypertensive medication, ultrafiltration volume, and dialysis parameters. Over the one-year period, predialytic systolic blood pressure decreased significantly, but similarly in both groups. Mean start and mean end cardiac output, stroke volume, total peripheral resistance, heart rate, and mean arterial pressure were stable and similar in the two groups, whereas central blood volume increased slightly but similarly over time. The mean hemodynamic response observed during a dialysis session was a drop in cardiac output, in stroke volume, in mean arterial pressure, and in central blood volume, whereas heart rate increased. Total peripheral resistance did not change significantly. Overall, this pattern remained stable over time in both groups and was uninfluenced by ARB treatment. The total number of intradialytic hypotensive episodes was (placebo/ARB) 50/63 (P = 0.4). Ultrafiltration volume, left ventricular mass index, plasma albumin, and change in intradialytic total peripheral resistance were significantly associated with intradialytic hypotension in a multivariate logistic regression analysis based on baseline parameters. CONCLUSION: Use of the ARB irbesartan as an add-on to other antihypertensive therapy did not significantly affect intradialytic hemodynamics, neither in short nor long-term, and no significant increase in hypotensive episodes was seen. TRIAL REGISTRATION: Clinicaltrials.gov NCT00791830.

Angiotensin blockade and progressive loss of kidney function in hemodialysis patients: a randomized controlled trial.

BACKGROUND: Glomerular filtration rate (GFR) declines during long-term dialysis treatment. In peritoneal dialysis, blockade of the renin-angiotensin-aldosterone system reduces GFR decline. Observational studies suggest that similar treatment may preserve kidney function in hemodialysis (HD). STUDY DESIGN: A multicenter, randomized, placebo-controlled, double-blinded trial, with 1-year follow-up. SETTING & PARTICIPANTS: Adult HD patients with urine output >300mL/24h, HD vintage less than 1 year, and cardiac ejection fraction >30%. Patients were included from 6 HD centers. INTERVENTION: Patients were randomly assigned to placebo or the angiotensin II receptor blocker irbesartan, 300mg daily. Target systolic blood pressure (BP) was 140mm Hg. OUTCOMES & MEASUREMENTS: Primary outcomes were change in GFR measured as the mean of creatinine and urea renal clearance together with urine volume. Secondary outcomes were change in albuminuria, renin-angiotensin II-aldosterone hormone plasma levels, and time to anuria. RESULTS: Of 82 patients randomly assigned (41 patients in each group), 56 completed 1 year of treatment. The placebo and irbesartan groups were comparable at baseline in terms of sex balance (26 vs 30 men), mean age (62 vs 61 years), median HD vintage (137 vs 148 days), mean HD time (10 vs 11h/wk), median urine volume (1.19 vs 1.26L/d), and mean GFR (4.8 vs 5.7mL/min/1.73m(2)). The target BP level was reached in both groups and BP did not differ significantly between groups over time. Adverse-event rates were similar. GFR declined by a mean of 1.7 (95% CI, 1.2-2.3) and 1.8 (95% CI, 1.1-2.4) mL/min/1.73m(2) per year in the placebo and irbesartan groups, respectively. Mean difference (baseline values minus value at 12 months) between groups was -0.0 (95% CI, -0.8 to 0.8). In each group, 4 patients became anuric. LIMITATIONS: GFR decline rates were lower than expected, reducing the power. CONCLUSIONS: At equal BP levels, we found that irbesartan treatment did not affect the decline in GFR or urine volume significantly during 1 year of treatment in HD patients. Irbesartan treatment was used safely in the studied population.

Invasive validation of arteriograph estimates of central blood pressure in patients with type 2 diabetes.

BACKGROUND: Central blood pressure (BP) has attracted increasing interest because of a potential superiority over brachial BP in predicting cardiovascular morbidity and mortality. Several devices estimating central BP noninvasively are now available. The aim of our study was to determine the validity of the Arteriograph, a brachial cuff-based, oscillometric device, in patients with type 2 diabetes. METHODS: We measured central BP invasively and compared it with the Arteriograph-estimated values in 22 type 2 diabetic patients referred to elective coronary angiography. RESULTS: The difference (invasively measured BP minus Arteriograph-estimated BP) in central systolic BP (SBP) was 4.4±8.7 mm Hg (P = 0.03). The limits of agreement were ±17.1 mm Hg. CONCLUSIONS: Compared with invasively measured central SBP, we found a systematic underestimation by the Arteriograph. However, the limits of agreement were similar to the previous Arteriograph validation study and to the invasive validation studies of other brachial cuff-based, oscillometric devices. A limitation in our study was the large number of patients (n = 14 of 36) in which the Arteriograph was unable to analyze the pressure curves. In a research setting, the Arteriograph seems applicable in patients with type 2 diabetes. CLINICAL TRAIL REGISTRATION: ClinicalTrials.gov ID NCT01538290.

Renal and cardiovascular effects of irbesartan in dialysis patients--a randomized controlled trial protocol (SAFIR study).

INTRODUCTION: Cardiovascular (CV) events are a major cause of morbidity and mortality in haemodialysis (HD) patients. Hypertension, increased arterial stiffness and left ventricular (LV) hypertrophy are highly prevalent and are often poorly controlled. Volume overload is an important factor and survival could be improved by treatment strategies that preserve residual renal function (RRF), reduce blood pressure, and decrease arterial stiffness and LV hypertrophy. Angiotensin II receptor blocker (ARB) treatment can prevent CV events in patients with hypertension and heart failure. However, few data exist in patients with chronic renal failure and it is not known whether ARB treatment improves clinical outcome in HD patients. MATERIAL AND METHODS: This is a randomized, controlled and double-blinded intervention study. A total of 82 HD patients from six Danish HD centres will be treated for a year with an ARB (irbesartan) or placebo. The inclusion criteria are urine output > 300 ml/day, dialysis vintage < 1 year and LV ejection fraction > 30%. The primary outcomes are change in RRF, LV hypertrophy, arterial stiffness and intra-dialytic haemodynamics. CONCLUSION: If ARB-treatment improves RRF and intermediate CV endpoints in a group of newly started HD patients, it may improve the survival for this high risk population. FUNDING: The trial is investigator-initiated, investigator-driven and supported by the Danish Agency for Science, Technology and Innovation and several private foundations.

[Participation in dinner at a medical conference reduces vascular age and is recommended]. / Deltagelse i konferencemiddag reducerer den vaskulære alder og anbefales af helbredsmæssige grunde

A total of 60 attendees at a medical conference had their peripheral and central blood pressure measured before and after the conference dinner. While heart rate increased, all measurements of peripheral and central blood pressure showed lower values after dinner. Furthermore, attendees' central vascular age was reduced by 13 years after dinner when augmentation index was evaluated in relation to age. Although 13% experienced postprandial hypotension, the present study motivates attendance at medical conference dinners due to the health implications of lowered blood pressure.

Preserving residual renal function in dialysis patients: an update on evidence to assist clinical decision making.

It has been documented that preservation of residual renal function in dialysis patients improves quality of life as well as survival. Clinical trials on strategies to preserve residual renal function are clearly lacking. While waiting for more results from clinical trials, patients will benefit from clinicians being aware of available knowledge. The aim of this review was to offer an update on current evidence assisting doctors in clinical practice.

Effects of phosphodiesterase-5 inhibition by sildenafil in the pressure overloaded right heart.

BACKGROUND: Sustained pressure overload of the right ventricle (RV) causes RV hypertrophy and failure. Cyclic-GMP has previously been shown to modulate left ventricular hypertrophy. AIM: To evaluate the effects of sildenafil, a phosphodiesterase-5 (PDE5) inhibitor elevating c-GMP, on myocardial hypertrophy and function in rats with RV hypertrophy. METHODS: Rats were pulmonary trunk banded (PTB) and randomized to receive sildenafil (SIL) or vehicle (VEC) for three (n=14) and nine weeks (n=18). In addition, rats with established RV hypertrophy were randomized to SIL or VEC (n=17) three weeks after PTB. Right ventricular function was evaluated by echocardiography and RV hypertrophy by histology and RV weight. RESULTS: Sildenafil failed to inhibit the development of RV hypertrophy when given for both 3 and 9 weeks. On the contrary, sildenafil increased RV hypertrophy after 3 weeks (RV/bodyweight: SIL 0.099+/-0.016 vs. VEC 0.081+/-0.011; p<0.05) and total heart weight after 9 weeks (SIL 1.05+/-0.10 vs. VEC 0.93+/-0.08 g; p<0.05). Sildenafil also failed to reverse established RV hypertrophy, but significantly improved RV myocardial function as measured by Tricuspid Annular Plane Systolic Excursion (TAPSE: SIL 1.85+/-0.027 vs. VEC 1.39+/-0.037 mm; p<0.05). CONCLUSION: PDE5 inhibition by sildenafil failed to prevent or reverse RV hypertrophy in rats operated by pulmonary trunk banding. It actually increased RV hypertrophy and improved RV contractile function when given to rats with established RV hypertrophy.