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This study aimed to determine whether early administration of drugs that block the renin–angiotensin system slows the progression of change in glomerular mesangial fractional volume and retinopathy progression of two steps or more, according to the retinopathy severity scale. Early blockade of the renin–angiotensin system did not modify nephropathy progression in patients with type 1 diabetes but had important effects in slowing retinopathy. Early blockade of the renin–angiotensin system did not modify nephropathy progression in patients with type 1 diabetes but had important effects in slowing retinopathy. Diabetic nephropathy, responsible for more than 45% of cases of end-stage renal disease in the United States, 1 may be structurally advanced once albuminuria becomes detectable. 2 , 3 Blockers of the renin–angiotensin system are more effective than other antihypertensive agents in slowing nephropathy progression in patients who have proteinuria, diabetes mellitus, and a reduced glomerular filtration rate (GFR), 4 – 6 and such blockers can also decrease proteinuria in patients with diabetes. 7 Although the reduction of proteinuria in patients with diabetes has been associated with a reduction in the rate of decline in GFR in small studies, 8 this association has not been systematically tested; . . .

Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage. The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101. 784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13·4%]) and ramipril (1150 [13·5%]; hazard ratio [HR] 1·00, 95% CI 0·92–1·09), but was increased with combination therapy (1233 [14.5%]; HR 1·09, 1·01–1·18, p=0·037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2·21%]) and ramipril (174 [2·03%]; HR 1·09, 0·89–1·34) and more frequent with combination therapy (212 [2·49%]: HR 1·24, 1·01–1·51, p=0·038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (−2·82 [SD 17·2] mL/min/1·73 m 2 vs −4·12 [17·4], p<0·0001) or combination therapy (−6·11 [17·9], p<0·0001). The increase in urinary albumin excretion was less with telmisartan (p=0·004) or with combination therapy (p=0·001) than with ramipril. In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes. Boehringer-Ingelheim.

Patients with vasodilatory shock were randomly assigned to angiotensin II or placebo. At 3 hours, more patients in the angiotensin II group than in the placebo group had an increase in mean arterial pressure of at least 10 mm Hg or to at least 75 mm Hg.

In this study, patients with type 2 diabetes, albuminuria, and mild-to-moderate renal dysfunction received losartan followed by lisinopril or placebo. The study was stopped early because of increased risks of hyperkalemia and acute kidney injury with combination therapy. Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in the United States. 1 Persons with diabetes and proteinuria are at high risk for progression to ESRD. 2 Blockade of the renin–angiotensin system decreases the progression of proteinuric kidney disease, 3 – 5 and the degree of reduction in proteinuria correlates with the extent to which the decrease in the glomerular filtration rate (GFR) is slowed. 2 , 6 Given these observations, it has been hypothesized that interventions that further lower proteinuria will further reduce the risk of progression. 6 Combination therapy with an angiotensin-converting–enzyme (ACE) inhibitor and an angiotensin II–receptor blocker (ARB) results in . . .

Activation of the immune system is implicated in the Post-Acute Sequelae after SARS-CoV-2 infection (PASC) but the mechanisms remain unknown. Angiotensin-converting enzyme 2 (ACE2) cleaves angiotensin II (Ang II) resulting in decreased activation of the AT1 receptor and decreased immune system activation. We hypothesized that autoantibodies against ACE2 may develop after SARS-CoV-2 infection, as anti-idiotypic antibodies to anti-spike protein antibodies. We tested plasma or serum for ACE2 antibodies in 67 patients with known SARS-CoV-2 infection and 13 with no history of infection. None of the 13 patients without history of SARS-CoV-2 infection and 1 of the 20 outpatients that had a positive PCR test for SARS-CoV-2 had levels of ACE2 antibodies above the cutoff threshold. In contrast, 26/32 (81%) in the convalescent group and 14/15 (93%) of patients acutely hospitalized had detectable ACE2 antibodies. Plasma from patients with antibodies against ACE2 had less soluble ACE2 activity in plasma but similar amounts of ACE2 protein compared to patients without ACE2 antibodies. We measured the capacity of the samples to inhibit ACE2 enzyme activity. Addition of plasma from patients with ACE2 antibodies led to decreased activity of an exogenous preparation of ACE2 compared to patients that did not have antibodies. Many patients with a history of SARS-CoV-2 infection have antibodies specific for ACE2. Patients with ACE2 antibodies have lower activity of soluble ACE2 in plasma. Plasma from these patients also inhibits exogenous ACE2 activity. These findings are consistent with the hypothesis that ACE2 antibodies develop after SARS-CoV-2 infection and decrease ACE2 activity. This could lead to an increase in the abundance of Ang II, which causes a proinflammatory state that triggers symptoms of PASC.

Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome. We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6–40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794. Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12–28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of −0·22 mm per year (−0·41 to −0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means −0·10 per year, 95% CI −0·19 to −0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events. Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications. British Heart Foundation, the UK Marfan Trust, the UK Marfan Association.

This large trial compared the angiotensin-receptor blocker telmisartan, the angiotensin-converting–enzyme inhibitor ramipril, and combination therapy with both drugs in patients with vascular disease or high-risk diabetes. Outcomes were the same with telmisartan and ramipril, and there were more adverse events with combination therapy. This trial compared the angiotensin-receptor blocker telmisartan, the angiotensin-converting–enzyme inhibitor ramipril, and combination therapy in patients with vascular disease or high-risk diabetes. Outcomes were the same with telmisartan and ramipril, and there were more adverse events with combination therapy. Randomized, controlled trials involving about 150,000 patients have convincingly demonstrated that angiotensin-converting–enzyme (ACE) inhibitors reduce rates of death, myocardial infarction, stroke, and heart failure among patients with heart failure, 1 left ventricular dysfunction, 2 – 4 previous vascular disease alone, 5 – 7 or high-risk diabetes. 8 ACE inhibitors do not block the production of all angiotensin II, so direct receptor blockade might be more effective. ACE inhibitors reduce bradykinin degradation, which enhances vasodilatation, but increase the rates of angioedema and cough. In patients with heart failure, angiotensin II levels may increase and symptoms worsen, despite the use of ACE inhibitors. 9 The use of an angiotensin-receptor . . .

This study investigated whether an angiotensin-receptor blocker (olmesartan) would delay microalbuminuria in patients with type 2 diabetes and normoalbuminuria. Olmesartan was associated with a delayed onset of microalbuminuria, even though blood pressure control in both groups was excellent. Diabetic nephropathy is an increasingly common cause of end-stage renal disease, 1 and the development and rate of renal deterioration are most closely related to the patient's blood pressure. Guideline committees worldwide concur that the blood pressure in patients with diabetes and chronic kidney disease should be kept at 130/80 mm Hg or less. 2 Microalbuminuria is predictive of diabetic nephropathy and premature cardiovascular disease 3 – 5 ; therefore, European and American guidelines recommend that patients with diabetes be tested for microalbuminuria. 6 , 7 Overactivity of the renin–angiotensin system has been implicated in the deterioration of renal function in patients with diabetic nephropathy and . . .

This open-label trial randomly assigned patients with IgA nephropathy to supportive care or supportive care plus immunosuppression. The added immunosuppression did not significantly improve outcomes; more adverse events occurred, with no change in the rate of decrease in eGFR. IgA nephropathy is the most common form of glomerulonephritis. 1 Several findings support the use of immunosuppressive therapy to target mesangial IgA deposits and circulating IgA autoantibodies. 2 The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines regarding IgA nephropathy recommend treatment with a blocker of the renin–angiotensin system (i.e., an angiotensin-converting–enzyme inhibitor or an angiotensin II–receptor blocker) in patients who have proteinuria with urinary protein excretion of more than 1 g per day. 3 – 5 The KDIGO guidelines also suggest the use of systemic glucocorticoids in patients who have a proteinuria level above 1 g of urinary protein excretion per day and a . . .

In this study, children and young adults with Marfan's syndrome were randomly assigned to receive atenolol or losartan and were followed for 3 years. There was no significant difference between the two groups in the rate of aortic-root dilatation. Marfan's syndrome is an autosomal dominant disorder of connective tissue affecting approximately 1 in 5000 people. 1 Cardiovascular disease, mainly progressive aortic-root dilatation and dissection, is the leading cause of death in Marfan's syndrome. After an open-label, randomized trial comparing propranolol with no therapy, published in 1994, showed a reduced rate of aortic enlargement among treated patients, beta-adrenergic receptor antagonists (beta-blockers) became the mainstay of medical management. 2 Current management includes serial cardiac imaging, exercise restriction, administration of beta-blockers, and elective aortic-root replacement. 3 Although early diagnosis and refined medical and surgical treatment have improved survival, patients with Marfan's syndrome continue to have . . .