Adrenaline and hypertension

The questions we hoped to answer by the studies described in this thesis, were: 1 Does adrenaline, when infused intravenously in normotensive subjects leading to plasma levels in the high physiological range, cause a sustained and protracted rise in blood pressure, which outlasts the duration of the increments in circulating adrenaline? And if so, does this effect on blood pressure occurs at rest or during periods of activation of the sympathetic nervous system? In view of the data of Vincent et al (43), we hypothesized that the latter would be the case. 2 If the questions under number 1 are positively answered, does intravenous administered noradrenaline have the same effect? When the effect of adrenaline is indeed mediated through prejunctional B,-adrenoceptors, we hypothesized that this would not be the case. 3 Do the pressor responses to standardized sympathetic nervous system stimulation by cold pressor and isometric exercise testing before, during and 18 hours after cessation of infusions of adrenaline, noradrenaline or dextrose 5% differ? Again we hypothesized that infusion of adrenaline but not noradrenaline would lead to an amplification of the blood pressure responses. 4 Are the changes in plasma concentrations of adrenaline and noradrenaline during the infusions of adrenaline and noradrenaline also detectable in alterations in the amounts of catecholamines and their metabolites excreted in the urine? 5 Do the infusions of catechOiamines, which lead to alterations in plasma concentrations within the physiological range, have any effect on urinary sodium excretion or on plasma levels of several hormones, potassium or glucose? 6 What is the effect of non-selective and B,-selective B-blockade on the adrenaline mediated facilitation of noradrenaline release and the adrenaline induced enhancement of reflex sympathetic nervous system activity

Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension

We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week. Compared with placebo, 24-hour ambulatory blood pressure did not change with the 1-mg dose, and it fell (mean and 95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the 25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg dose. Heart rate did not change during either dose. With the 25-mg dose, the antihypertensive effect was attenuated during the second half of the recording, and wi

Short- and long-term functional effects of percutaneous transluminal angioplasty in hemodialysis vascular access

The efficacy of percutaneous transluminal angioplasty (PTA) is usually expressed as the angiographic result. Access flow (Qa) measurements offer a means to quantify the functional effects. This study was performed to evaluate the short-term functional and angiographic effects of PTA and to determine the longevity of the functional effects during the follow-up period. Patients with an arteriovenous graft (AVG) or an arteriovenous fistula (AVF) who were eligible for PTA (Qa values of <600 ml/min) were included. Ultrasound-dilution Qa measurements were obtained shortly before PTA and periodically after PTA, beginning 1 wk after the procedure. The short-term effects were expressed as the increase in Qa and the reduction of stenosis. The long-term effects were expressed as patency and the decrease in Qa after PTA. Ninety-eight PTA procedures for 60 patients (65 AVG and 33 AVF) were analyzed. Qa improved from 371 +/- 17 to 674 +/- 30 ml/min for AVG and from 304 +/- 24 to 638 +/- 51 ml/min for AVF (both P < 0.0001). In 66% (AVG) and 50% (AVF) of cases, Qa increased to levels of >600 ml/min. The degree of stenosis decreased from 65 +/- 3 to 17 +/- 2% for AVG and from 72 +/- 5 to 23 +/- 7% for AVF (both P < 0.005). The reduction of stenosis was not correlated with DeltaQa (r(2) = 0.066). Six-month unassisted patency rates after PTA were 25% for AVG and 50% for AVF. The decreases in Qa were 3.7 +/- 0.8 ml/min per d for AVG and 1.8 +/- 0.9 ml/min per d for AVF. Qa values before PTA and DeltaQa were correlated with the subsequent decrease in Qa (P < 0.005). In conclusion, Qa increases after PTA but, in a substantial percentage of cases, not to levels of >600 ml/min. Qa values before PTA and the increase in Qa were correlated with long-term outcomes, whereas angiographic results were not. These data, combined with literature data, suggest that there is optimal timing for PTA

The effect of online hemodiafiltration on infections: Results from the CONvective TRAnsport STudy

Background: Hemodialysis (HD) patients have a high risk of infections. The uremic milieu has a negative impact on several immune responses. Online hemodiafiltration (HDF) may reduce the risk of infections by ameliorating the uremic milieu through enhanced clearance of middle molecules. Since there are few data on infectious outcomes in HDF, we compared the effects of HDF with low-flux HD on the incidence and type of infections. Patients and Methods: We used data of the 714 HD patients (age 64 ±14, 62% men, 25% Diabetes Mellitus, 7% catheters) participating in the CONvective TRAnsport STudy (CONTRAST), a randomized controlled trial evaluating the effect of HDF as compared to low-flux HD. The events were adjudicated by an independent event committee. The risk of infectious events was compared with Cox regression for repeated events and Cox proportional hazard models. The distributions of types of infection were compared between the groups. Results: Thirty one percent of the patients suffered from one or more infections leading to hospitalization during the study (median follow-up 1.96 years). The risk for infections during the entire follow-up did not differ significantly between treatment arms (HDF 198 and HD 169 infections in 800 and 798 person-years respectively, hazard ratio HDF vs. HD 1.09 (0.88-1.34), P = 0.42. No difference was found in the occurrence of the first infectious event (either fatal, nonfatal or type specific). Of all infections, respiratory infections (25% in HDF, 28% in HD) were most common, followed by skin/musculoskeletal infections (21% in HDF, 13% in HD). Conclusions: HDF as compared to HD did not result in a reduced risk of infections, larger studies are needed to confirm our findings. Trial Registration: ClinicalTrials.gov NCT00205556

Serum magnesium and sudden death in European hemodialysis patients

Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome, the association with mortality in European hemodialysis (HD) patients has only scarcely been investigated. Furthermore, data on the association between serum Mg and sudden death in this patient group is limited. Therefore, we evaluated Mg in a posthoc analysis using pooled data from the CONvective TRAnsport STudy (CONTRAST, NCT00205556), a randomized controlled trial (RCT) evaluating the survival risk in dialysis patients on hemodiafiltration (HDF) compared to HD with a mean follow-up of 3.1 years. Serum Mg was measured at baseline and 6, 12, 24 and 36 months thereafter. Cox proportional hazards models, adjusted for confounders using inverse probability weighting, were used to estimate hazard ratios (HRs) of baseline serum Mg on all-cause mortality, cardiovascular mortality, non-cardiovascular mortality and sudden death. A generalized linear mixed model was used to investigate Mg levels over time. Out of 714 randomized patients, a representative subset of 365 (51%) were analyzed in the present study. For every increase in baseline serum Mg of 0.1 mmol/L, the HR for all-cause mortality was 0.85 (95% CI 0.77-94), the HR for cardiovascular mortality 0.73 (95% CI 0.62-0.85) and for sudden death 0.76 (95% CI 0.62-0.93). These findings did not alter after extensive correction for potential confounders, including treatment modality. Importantly, no interaction was found between serum phosphate and serum Mg. Baseline serum Mg was not related to non-cardiovascular mortality. Mg decreased slightly but statistically significant over time (Ä -0.011 mmol/L/year, 95% CI -0.017 to -0.009, p = 0.03). In short, serum Mg has a strong, independent association with all-cause mortality, cardiovascular mortality and sudden death in European HD patients. Serum Mg levels decrease slightly over time

Magnetic resonance imaging biomarkers for chronic kidney disease: a position paper from the European Cooperation in Science and Technology Action PARENCHIMA

Functional renal magnetic resonance imaging (MRI) has seen a number of recent advances, and techniques are now available that can generate quantitative imaging biomarkers with the potential to improve the management of kidney disease. Such biomarkers are sensitive to changes in renal blood flow, tissue perfusion, oxygenation and microstructure (including inflammation and fibrosis), processes that are important in a range of renal diseases including chronic kidney disease. However, several challenges remain to move these techniques towards clinical adoption, from technical validation through biological and clinical validation, to demonstration of cost-effectiveness and regulatory qualification. To address these challenges, the European Cooperation in Science and Technology Action PARENCHIMA was initiated in early 2017. PARENCHIMA is a multidisciplinary pan-European network with an overarching aim of eliminating the main barriers to the broader evaluation, commercial exploitation and clinical use of renal MRI biomarkers. This position paper lays out PARENCHIMA’s vision on key clinical questions that MRI must address to become more widely used in patients with kidney disease, first within research settings and ultimately in clinical practice. We then present a series of practical recommendations to accelerate the study and translation of these techniques

The effect of immunoscintigraphy with monoclonal antibodies on assays of hormones and tumor markers. This is not the end of the matter!

The use of monoclonal antibodies in medicine for in-vivo diagnostic methods and for therapeutic purposes will increase in the future. Although monoclonal antibodies possess a high specificity, the animal origin of these antibodies remains a problem. Repeated administration of animal monoclonal antibodies (in vivo) may induce the formation of human antibodies against these monoclonal antibodies. Because animal monoclonal antibodies are also used in laboratory assays (in vitro), the presence of human antibodies against these animal monoclonal antibodies may cause spuriously elevated or depressed results of these assays. The clinici

Nurse practitioner care improves renal outcome in patients with CKD

Treatment goals for patients with CKD are often unrealized for many reasons, but support by nurse practitioners may improve risk factor levels in these patients. Here, we analyzed renal endpoints of the Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners (MASTERPLAN) study after extended follow-up to determine whether strict implementation of current CKD guidelines through the aid of nurse practitioners improves renal outcome. In total, 788 patients with moderate to severe CKD were randomized to receive nurse practitioner support added to physician care (intervention group) or physician care alone (control group). Median follow-up was 5.7 years. Renal outcome was a secondary endpoint of the MASTERPLAN study. We used a composite renal endpoint of death, ESRD, and 50% increase in serum creatinine. Event rates were compared with adjustment for baseline serum creatinine concentration and changes in estimated GFR were determined. During the randomized phase, there were small but significant differences between the groups in BP, proteinuria, LDL cholesterol, and use of aspirin, statins, active vitamin D, and antihypertensive medications, in favor of the intervention group. The intervention reduced the incidence of the composite renal endpoint by 20% (hazard ratio, 0.80; 95% confidence interval, 0.66 to 0.98; P=0.03). In the intervention group, the decrease in estimated GFR was 0.45 ml/min per 1.73 m2 per year less than in the control group (P=0.01). Inconclusion, additionalsupport by nurse practitioners attenuatedthe declineof kidney function and improved renal outcome in patients with CKD. Copyrigh