Evidence and Consequences of the Central Role of the Kidneys in the Pathophysiology of Sympathetic Hyperactivity

Chronic elevation of the sympathetic nervous system has been identified as a major contributor to the complex pathophysiology of hypertension, states of volume overload – such as heart failure – and progressive kidney disease. It is also a strong determinant for clinical outcome. This review focuses on the central role of the kidneys in the pathogenesis of sympathetic hyperactivity. As a consequence, renal denervation may be an attractive option to treat sympathetic hyperactivity. The review will also focus on first results and the still remaining questions of this new treatment option

7 T renal MRI: challenges and promises

The progression to 7 Tesla (7 T) magnetic resonance imaging (MRI) yields promises of substantial increase in signal-to-noise (SNR) ratio. This increase can be traded off to increase image spatial resolution or to decrease acquisition time. However, renal 7 T MRI remains challenging due to inhomogeneity of the radiofrequency field and due to specific absorption rate (SAR) constraints. A number of studies has been published in the field of renal 7 T imaging. While the focus initially was on anatomic imaging and renal MR angiography, later studies have explored renal functional imaging. Although anatomic imaging remains somewhat limited by inhomogeneous excitation and SAR constraints, functional imaging results are promising. The increased SNR at 7 T has been particularly advantageous for blood oxygen level-dependent and arterial spin labelling MRI, as well as sodium MR imaging, thanks to changes in field-strength-dependent magnetic properties. Here, we provide an overview of the currently available literature on renal 7 T MRI. In addition, we provide a brief overview of challenges and opportunities in renal 7 T MR imaging

Education for the anthropocene : planetary health, sustainable health care, and the health workforce

Over the past few centuries, human activity has wrought dramatic changes in the natural systems that support human life. Planetary health is a useful concept for health profession education (HPE) teaching and practice because it situates health within a broader understanding of the interdependent socio-ecological drivers of human and planetary health. It facilitates novel ways of protecting both population health and the natural environment on which human health and wellbeing depends. This paper focuses on the climate crisis as an example of the relationship between environmental change, healthcare, and education. We analyze how HPE can help decarbonize the healthcare sector to address both climate change and inequity in health outcomes. Based on the healthcare practitioner’s mandate of beneficence, we propose simple learning objectives to equip HPE graduates with the knowledge, skills, and values to create a sustainable health system, using carbon emission reductions as an example. These learning objectives can be integrated into HPE without adding unduly to the curriculum load

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

Resistance to erythropoiesis stimulating agents in patients treated with online hemodiafiltration and ultrapure low-flux hemodialysis: Results from a randomized controlled trial (CONTRAST)

Resistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this analysis of the randomized controlled CONvective TRAnsport STudy (CONTRAST; NCT00205556), the effect of online HDF on ESA resistance and iron parameters was studied. This was a prespecified secondary endpoint of the main trial. A 12 months' analysis of 714 patients randomized to either treatment with online post-dilution HDF or continuation of low-flux HD was performed. Both groups were treated with ultrapure dialysis fluids. ESA resistance, measured every three months, was expressed as the ESA index (weight adjusted weekly ESA dose in daily defined doses [DDD]/hematocrit). The mean ESA index during 12 months was not different between patients treated with HDF or HD (mean difference HDF versus HD over time 0.029 DDD/kg/Hct/week [20.024 to 0.081]; P = 0.29). Mean transferrin saturation ratio and ferritin levels during the study tended to be lower in patients treated with HDF (22.52% [24.72 to 20.31]; P = 0.02 and 249 ng/mL [2103 to 4]; P = 0.06 respectively), although there was a trend for those patients to receive slightly more iron supplementation (7.1 mg/week [20.4 to 14.5]; P = 0.06). In conclusion, compared to low-flux HD with ultrapure dialysis fluid, treatment with online HDF did not result in a decrease in ESA resistance

Blood pressure response to renal denervation is correlated with baseline blood pressure variability: a patient-level meta-analysis

Background: Sympathetic tone is one of the main determinants of blood pressure (BP) variability and treatment-resistant hypertension. The aim of our study was to assess changes in BP variability after renal denervation (RDN). In addition, on an exploratory basis, we investigated whether baseline BP variability predicted the BP changes after RDN. Methods: We analyzed 24-h BP recordings obtained at baseline and 6 months after RDN in 167 treatmentresistant hypertension patients (40% women; age, 56.7 years; mean 24-h BP, 152/90 mmHg) recruited at 11 expert centers. BP variability was assessed by weighted SD [SD over time weighted for the time interval between consecutive readings (SDiw)], average real variability (ARV), coefficient of variation, and variability independent of the mean (VIM). Results: Mean office and 24-h BP fell by 15.4/6.6 and 5.5/ 3.7 mmHg, respectively (P &lt; 0.001). In multivariable-adjusted analyses, systolic/diastolic SDiw and VIM for 24-h SBP/DBP decreased by 1.18/0.63 mmHg (P 0.01) and 0.86/0.42 mmHg (P 0.05), respectively, whereas no significant changes in ARV or coefficient of variation occurred. Furthermore, baseline SDiw (P ¼ 0.0006), ARV (P ¼ 0.01), and VIM (P ¼ 0.04) predicted the decrease in 24-h DBP but not 24-h SBP after RDN. Conclusion: RDN was associated with a decrease in BP variability independent of the BP level, suggesting that responders may derive benefits from the reduction in BP variability as well. Furthermore, baseline DBP variability estimates significantly correlated with mean DBP decrease after RDN. If confirmed in younger patients with less arterial damage, in the absence of the confounding effect of drugs and drug adherence, baseline BP variability may prove a good predictor of BP response to RDN

Development of a clinical decision tool to reduce diagnostic testing for primary aldosteronism in patients with difficult-to-control hypertension

BACKGROUND: Satisfactory tools to preclude low-risk patients from intensive diagnostic testing for primary aldosteronism (PA) are lacking. Therefore, we aimed to develop a decision tool to determine which patients with difficult-to-control hypertension have a low probability of PA, thereby limiting the exposure to invasive testing while at the same time increasing the efficiency of testing in the remaining patients. METHODS: Data from consecutive patients with difficult-to-control hypertension, analysed through a standardized diagnostic protocol between January 2010 and October 2017 (n = 824), were included in this cross-sectional study. PA was diagnosed by a combined approach: 1) elevated aldosterone-to-renin ratio (> 5.0 pmol/fmol/s), confirmed with 2) non-suppressible aldosterone after standardized saline infusion (≥280 pmol/L). Multivariable logistic regression analyses including seven pre-specified clinical variables (age, systolic blood pressure, serum potassium, potassium supplementation, serum sodium, eGFR and HbA1c) was performed. After correction for optimism, test reliability, discriminative performance and test characteristics were determined. RESULTS: PA was diagnosed in 40 (4.9%) of 824 patients. Predicted probabilities of PA agreed well with observed frequencies and the c-statistic was 0.77 (95% confidence interval (95%CI) 0.70-0.83). Predicted probability cut-off values of 1.0-2.5% prevented unnecessary testing in 8-32% of the patients with difficult-to-control hypertension, carrying sensitivities of 0.98 (95%CI 0.96-0.99) and 0.92 (0.83-0.97), and negative predictive values of 0.99 (0.98-1.00) and 0.99 (0.97-0.99). CONCLUSIONS: With a decision tool, based on seven easy-to-measure clinical variables, patients with a low probability of PA can be reliably selected and a considerable proportion of patients with difficult-to-control hypertension can be spared intensive diagnostic testing