The effect of renal artery angioplasty on blood pressure in patients with true resistant hypertension and atherosclerotic renal artery stenosis has not been fully investigated due to the exclusion of ...these patients from most trials. In this study, we assessed the benefits of renal angioplasty on daytime ambulatory blood pressure (dABP) in this subgroup of patients. Medical records of our hypertension department were retrospectively analyzed from 2000 to 2016. Seventy-two patients were identified with resistant hypertension (dABP >135 or 85 mm Hg despite at least 3 antihypertensive drugs, including a diuretic) and atherosclerotic renal artery stenosis treated by angioplasty. Atherosclerotic renal artery stenosis was unilateral in 57 patients and bilateral in 15 patients. The mean age of the patients was 67.8±11.2 years; dABP was 157±16/82±10 mm Hg despite 4.0±1.0 antihypertensive treatments; estimated glomerular filtration rate was 52 (41-63) mL/min. After renal angioplasty, dABPM decreased by 14.0±17.3/6.4±8.7 mm Hg (
<0.001 for both), and the number of antihypertensive treatments decreased to 3.6±1.4 (
=0.002) with no significant change in estimated glomerular filtration rate. A high baseline systolic dABP and a low body mass index were independent predictors of systolic dABP changes. The decrease in dABP was confirmed in a subgroup of patients at one and 3 years of follow-up (N=31 and N=18 respectively,
≤0.001 for systolic and diastolic blood pressure at both visits). In this retrospective uncontrolled single-center study, angioplasty in patients with atherosclerotic renal artery stenosis and with true resistant hypertension significantly decreased dABP, reducing the need for antihypertensive treatment with no change in estimated glomerular filtration rate.
The indication of percutaneous renal transluminal angioplasty (PTRA) in fibromuscular dysplasia (FMD) is mainly based on renal artery stenosis (RAS) due to atherosclerosis criteria, which are not ...specific to FMD. Consequently, the selection of patients who could benefit from this treatment and its effectiveness remain uncertain. The aims of this study were to: (1) report the effects of PTRA guided by trans-stenotic pressure measurements on hypertension 7 months after treatment; (2) assess the impact of pressure measurement to guide treatment efficacy in comparison to visual angiographic parameters; and (3) evaluate the reproducibility and accuracy of the stenosis measurement using a 4F catheter in comparison to a pressure guidewire.
This prospective multi-centric study analyzed 24 patients with hypertension with RAS due to FMD that required PTRA. Clinical, duplex ultrasound, and angiographic indices were collected, and patients were followed up for 7 months (±1 month). Angiographic indices were measured twice both by a pressure guidewire and a 4F catheter. Assessment of procedural and clinical success of angioplasty was performed for all patients.
Twenty-three patients (96%) had procedural success (considered as a post-PTRA translesional systolic gradient ≤10 mmHg or reduced by at least 80%) with a significant decrease in the systolic gradient after angioplasty (26.50 mmHg; interquartile range, 16.75-38.75 vs 0.00 interquartile range, 0.00-2.00; P < .01). Three patients (12%) had complications, including two renal artery dissections and one partial renal infarction. Twenty-one patients (88%) were clinical responders to angioplasty at follow-up. Visual stenosis assessment showed a poor correlation with systolic gradient measurement before and after PTRA (R from −0.05 to 0.41; P = 0.06-0.82). High correlations were found between pressure measurements made by a 4F catheter and guidewire (R from 0.64 to 0.89; P ≤ .003).
In patients selected by clinical indicators and duplex ultrasound, reaching a translesional systolic gradient ≤10 mmHg or reduced by at least 80% after angioplasty, promotes a high success rate for PTRA in hypertension due to FMD RAS.
In the selected population, percutaneous renal transluminal angioplasty guided by trans-stenotic pressure showed a beneficial effect on hypertension management in 88% of patients with initial trans-stenotic gradient. Assessment of systolic gradient measurement is more reliable than visual stenosis assessment for guiding percutaneous renal transluminal angioplasty. Trans-stenotic pressure assessment using a 4F catheter is reproducible and highly correlated with assessments made through a pressure guidewire.
Abstract
Background
In rodents, the stimulation of adrenal progesterone is necessary for renal adaptation under potassium depletion. Here, we sought to determine the role of progesterone in adrenal ...adaptation in potassium-depleted healthy human volunteers and compared our findings with data collected in patients with Gitelman syndrome (GS), a salt-losing tubulopathy.
Methods
Twelve healthy young men were given a potassium-depleted diet for 7 days at a tertiary referral medical centre (NCT02297048). We measured by liquid chromatography coupled to tandem mass spectroscopy plasma steroid concentrations at Days 0 and 7 before and 30 min after treatment with tetracosactide. We compared these data with data collected in 10 GS patients submitted to tetracosactide test.
Results
The potassium-depleted diet decreased plasma potassium in healthy subjects by 0.3 ± 0.1 mmol/L, decreased plasma aldosterone concentration by 50% (P = 0.0332) and increased plasma 17-hydroxypregnenolone concentration by 45% (P = 0.0232) without affecting other steroids. CYP17 activity, as assessed by 17-hydroxypregnenolone/pregnenolone ratio, increased by 60% (P = 0.0389). As compared with healthy subjects, GS patients had 3-fold higher plasma concentrations of aldosterone, 11-deoxycortisol (+30%) and delta 4-androstenedione (+14%). Their post-tetracosactide progesterone concentration was 2-fold higher than that of healthy subjects and better correlated to plasma potassium than to plasma renin.
Conclusion
The increase in 17-hydroxypregnenolone concentration after mild potassium depletion in otherwise healthy human subjects suggests that 17 hydroxylation of pregnenolone prevents the increase in progesterone observed in potassium-depleted mice. The unexpected over-response of non-mineralocorticoid steroids to tetracosactide in GS subjects suggests that the adrenal system not only adapts to sodium depletion but may also respond to hypokalaemia.
Mineralocorticoid receptor antagonists have been used in patients with aldosterone-producing adenomas (APAs) as a test designed to predict the blood pressure (BP) outcome of surgery. They are ...commonly used in patients undergoing adrenalectomy to reduce BP and increase plasma potassium levels during the preoperative period. A small number of studies have compared the effects of surgery and mineralocorticoid antagonists either on BP, on serum potassium levels, or on the incidence of cardiovascular and renal outcomes in patients with primary aldosteronism with or without an APA; these studies found no difference between the two therapeutic options. Mineralocorticoid receptor antagonists can be used as a maintenance treatment for patients with APAs, who are judged to be poor operative risks or who do not want to undergo surgery.
Autosomal dominant polycystic kidney disease (ADPKD) is a renal hereditary disorder associated with increased cardiovascular mortality, due to mutations in polycystin-1 and polycystin-2 genes. ...Endothelial polycystin-deficient cells have an altered mechanosensitivity to fluid shear stress and subsequent deficit in calcium-induced nitric oxide release, prevented by dopamine receptor stimulation. However, the impact of polycystin deficiency on endothelial function in ADPKD patients is still largely unknown. Here we assessed endothelium-dependent flow-mediated dilatation in 21 normotensive ADPKD patients and 21 healthy control subjects, during sustained (hand skin heating) and transient (postischemic hyperemia) flow stimulation. Flow-mediated dilatation was less marked in ADPKD patients than in controls during heating, but it was similar during postischemic hyperemia. There was no difference in endothelium-independent dilatation in response to glyceryl trinitrate. Local plasma nitrite, an indicator of nitric oxide availability, increased during heating in controls but not in patients. Brachial infusion of dopamine in a subset of ADPKD patients stimulated plasma nitrite increase during heating and improved flow-mediated dilatation. Thus, ADPKD patients display a loss of nitric oxide release and an associated reduction in endothelium-dependent dilatation of conduit arteries during sustained blood flow increase. The correction of these anomalies by dopamine suggests future therapeutic strategies that could reduce the occurrence of cardiovascular events in ADPKD.
Resistant hypertension is defined as uncontrolled blood pressure (BP) despite three antihypertensive agents including a diuretic (thiazide diuretic if renal function is normal or loop diuretic in ...case of chronic kidney disease with eGFR<30mL/min), a renin-angiotensin system blocker (ARB or ACEI) and a calcium channel blocker, at optimal doses. Resistance must be confirmed by out-of-office measurements (ambulatory blood pressure monitoring or home blood pressure monitoring) and patients should be asked about treatment compliance and excessive salt or alcohol intake. If the diagnosis of resistant hypertension is confirmed, the patient should be referred to a hypertension specialist to screen for secondary causes of hypertension as they are frequent in this context. If essential resistant hypertension is confirmed, the mineralocorticoid receptor antagonist, spironolactone, should be added (25 to 50mg daily). In the event of a contraindication to spironolactone, or if adverse effects occur, a beta-blocker, an alpha-blocker, or a centrally acting antihypertensive drug should be prescribed.
There is a persistent need for the development of new antihypertensive drugs, because the control of blood pressure is still not achievable in a significant proportion of hypertensive patients. Since ...the approval in 2007 of aliskiren, no other new antihypertensive based on new mechanism(s) of action have been approved. In fact, the development of promising novel drugs has been stopped for safety, efficacy or marketing reasons. Despite these difficulties, the pipeline is not dry and different new antihypertensive strategies targeting the renin-angiotensin-aldosterone pathway, are in clinical development stage. The dual angiotensin II receptor-neprilysin inhibitor LCZ696, a single molecule synthetized by cocrystallisation of valsartan and the neprilysin inhibitor prodrug AHU377 is in development for resistant hypertension and for heart failure. Daglutril is a dual neprylisin-endothelin converting enzyme inhibitor which was shown to decrease BP in patients with type 2 diabetic nephropathy. Aldosterone synthase inhibitors and the third and fourth generation non-steroidal dihydropyridine based mineralocorticoid receptors blockers are new ways to target the multiple noxious effects of aldosterone in the kidney, vessels and heart. Centrally acting aminopeptidase A inhibitors block brain angiotensin III formation, one of the main effector peptides of the brain renin angiotensin system. However, a long time will be still necessary to evaluate extensively the efficacy and safety of these new approaches. In the mean time, using appropriate and personalized daily doses of available drugs, decreasing physician inertia, improving treatment adherence, improving access to healthcare and reducing treatment costs remain major objectives to reduce the incidence of resistant hypertension.
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