Abstract-Some evidence suggests that long-term angiotensin-converting enzyme (ACE) inhibition may become less effective, thereby increasing angiotensin II levels, which could be inhibited by the addition of an angiotensin receptor blocker. We conducted a meta-analysis of randomized trials with searches of MEDLINE, EMBASE, and Cochrane databases. Overall, the combination of an ACE inhibitor and an angiotensin receptor blocker reduced ambulatory blood pressure by 4.7/3.0 mm Hg (95% confidence interval [CI], 2.9 to 6.5/1.6 to 4.3) compared with ACE inhibitor monotherapy and 3.8/2.9 mm Hg (2.4 to 5.3/0.4 to 5.4) compared with angiotensin receptor blocker monotherapy. Clinic blood pressure was reduced by 3.8/2.7 mm Hg (0.9 to 6.7/0.8 to 4.6) and 3.7/2.3 mm Hg (0.4 to 6.9/0.2 to 4.4) compared with ACE inhibitor and angiotensin receptor blocker, respectively. However, the majority of these studies used submaximal doses or once-daily dosing of shorter-acting ACE inhibitors and, when a larger dose of shorter-acting ACE inhibitor was given or a longer-acting ACE inhibitor was used, there was generally no additive effect of the angiotensin receptor blocker on blood pressure. Proteinuria was reduced by the combination compared with ACE inhibitor and angiotensin receptor blocker monotherapy, an effect that was independent of blood pressure in several studies, suggesting that the combination could have benefits in proteinuric nephropathies. None of the studies was of sufficient size and duration to determine whether there may be safety concerns. In conclusion, although there is a small additive effect on blood pressure with an ACE inhibitor-angiotensin receptor blocker combination, the routine use of this combination in uncomplicated hypertension is not recommended until more carefully controlled studies are performed. Key Words: angiotensin-converting enzyme Ⅲ hypertension Ⅲ meta-analysis Ⅲ proteinuria Ⅲ receptors, angiotensin Ⅲ renin-angiotensin system T he renin-angiotensin system (RAS) plays an important role in regulating blood pressure (BP). 1,2 Both angiotensinconverting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) inhibit the RAS and have been shown to be effective treatments for increased BP. 3 At the same time, they have other beneficial effects that may be independent of their ability to lower BP, for example, reductions in the progression of nephropathy in diabetes mellitus (DM) and chronic renal failure (CRF). 4 -6 Administration of ACEI causes plasma levels of angiotensin II (Ang II) to become undetectable, whereas there is some evidence that chronic administration of ACEI results in partial escape, ie, there is incomplete suppression of Ang II levels at peak, which may reduce the effectiveness of ACEI as BP-lowering agents. [7][8][9] Several studies have suggested that combining an ARB with an ACEI may provide a more complete blockade of the RAS in the treatment of diabetic and nondiabetic nephropathy and essential hypertension; in particular, it may lower BP and proteinuria furt...

This is the largest reported confirmed IE series in dialysis patients. Infective endocarditis in HD patients remains a challenging problem-although hemoaccess via dual-lumen catheters remains a significant risk, many cases developed in patients with AVFs and this group suffered the greatest mortality. An abnormal valve (frequently calcified) was another risk factor; because valve calcification is now common after 5 years on dialysis, more effort in preventing this avoidable form of ectopic calcification may reduce the risk of developing IE.

Activation of the classic circulating RAS is no greater in hypertensive ADPKD patients than in individuals with essential hypertension.

Raised blood pressure (BP) is extremely common in individuals with autosomal dominant polycystic kidney disease (ADPKD) and is almost invariably raised once they develop renal failure. The underlying mechanisms for the rise in BP in individuals with ADPKD are unclear. The progressive number and enlargement of renal cysts, causing structural damage to the kidneys and, thereby, affecting tubular function as well as causing distortion of the glomeruli and renal ischaemia, is likely to be of primary importance.There is some evidence from animal models that there may be over-activity of the intra-renal renin-angiotensin system (RAS) that could account for the rise in BP. Studies in man have shown conflicting results, but a recent more carefully controlled study using both measurements of activity and pharmacological blockade of the RAS clearly demonstrated no evidence of over-activity of the circulating RAS in ADPKD compared to matched individuals with essential hypertension.A more likely explanation for the rise in BP that occurs in ADPKD is retention of sodium and water due to tubular damage. Disappointingly, in spite of good evidence that RAS blocking drugs slow the progression of other renal, particularly glomerular, diseases, there is little evidence to suggest this is true for patients with ADPKD. Nevertheless, there is no doubt that lowering BP in ADPKD is just as important, if not more important, as in essential hypertension to prevent cardiovascular disease and strokes, with a recommended BP target of < 120/80 mmHg.

BackgroundRenal denervation (RDN) may lower blood pressure (BP); however, it is unclear whether medication changes may be confounding results. Furthermore, limited data exist on pattern of ambulatory blood pressure (ABP) response—particularly in those prescribed aldosterone antagonists at the time of RDN.MethodsWe examined all patients treated with RDN for treatment-resistant hypertension in 18 UK centres.ResultsResults from 253 patients treated with five technologies are shown. Pre-procedural mean office BP (OBP) was 185/102 mmHg (SD 26/19; n = 253) and mean daytime ABP was 170/98 mmHg (SD 22/16; n = 186). Median number of antihypertensive drugs was 5.0: 96 % ACEi/ARB; 86 % thiazide/loop diuretic and 55 % aldosterone antagonist. OBP, available in 90 % at 11 months follow-up, was 163/93 mmHg (reduction of 22/9 mmHg). ABP, available in 70 % at 8.5 months follow-up, was 158/91 mmHg (fall of 12/7 mmHg). Mean drug changes post RDN were: 0.36 drugs added, 0.91 withdrawn. Dose changes appeared neutral. Quartile analysis by starting ABP showed mean reductions in systolic ABP after RDN of: 0.4; 6.5; 14.5 and 22.1 mmHg, respectively (p < 0.001 for trend). Use of aldosterone antagonist did not predict response (p > 0.2).ConclusionIn 253 patients treated with RDN, office BP fell by 22/9 mmHg. Ambulatory BP fell by 12/7 mmHg, though little response was seen in the lowermost quartile of starting blood pressure. Fall in BP was not explained by medication changes and aldosterone antagonist use did not affect response.Electronic supplementary materialThe online version of this article (doi:10.1007/s00392-015-0959-4) contains supplementary material, which is available to authorized users.

ImportanceUltrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important.ObjectiveTo characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy.Data SourcesA Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials.Study SelectionTrials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up.Data Extraction and SynthesisPooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials.Main Outcomes and MeasuresThe primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups.ResultsA total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, −5.9; 95% CI, −8.1 to −3.8 mm Hg; P &amp;lt; .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: −10.4 mm Hg vs −3.4 mm Hg; mean difference, −6.4 mm Hg; 95% CI, −9.1 to –3.6 mm Hg; home SBP: −8.4 mm Hg vs −1.4 mm Hg; mean difference, −6.8 mm Hg; 95% CI, −8.7 to −4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups.Conclusions and RelevanceResults of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups.Trial RegistrationClinicalTrials.gov Identifier: NCT02649426 and NCT03614260

ACE Inhibitors (ACEI) and angiotensin receptor blockers (ARB) inhibit the renin-angiotensin system, but ACEI may do so incompletely when administered as monotherapy at conventional doses. In theory, combining an ACEI and ARB might be beneficial, whereas clinical evidence for this approach in hypertension is lacking. An ACEI-ARB combination is likely to be useful in proteinuric renal disease, but recent experimental evidence suggests that very high dose monotherapy with an ARB may be the best approach. However, the results of large outcome studies for combinations vs. ACEI or ARB monotherapy are still awaited.

This review outlines the major mechanisms for control of blood pressure (BP) in individuals with renal failure on haemodialysis. Dietary salt stimulates thirst and, thereby, greater fluid intake with excessive fluid gain between dialysis sessions and chronic expansion of extracellular volume. At the same time, this volume expansion often fails to suppress the renin-angiotensin system (RAS) appropriately and this inevitably leads to high BP in the majority of individuals on haemodialysis. A greater understanding of the mechanisms involved leads to more rational treatment and better BP control. This can be achieved by careful measurement of BP before and after dialysis, allowing time for the equilibration of extracellular fluid shifts that occur after dialysis, combined with measurements of plasma renin activity. It is relatively easy to then decide how the high BP should be treated: either by removal of excess volume by gradual ultrafiltration combined with restriction of salt intake to help prevent thirst and excessive fluid gain between dialyses, or by inhibition of the RAS, or by a combination of both. In those individuals who are unable to adequately reduce their dietary salt intake and still continue to gain large amounts of weight between dialysis, and are resistant to reducing their pre-dialysis weight, calcium antagonists may help to lower BP, either alone or in combination with RAS blockade. However, the BP often remains resistant to treatment unless they can be persuaded to reduce their salt intake.