UMLS:C0033687 - FACTA Search

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Query: UMLS:C0033687 (proteinuria)
24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ramipril is safe and effective in the treatment of hypertension and heart failure, but this is not reviewed here. Ramipril is a lipophilic angiotensin-converting enzyme inhibitor suitable for once-daily administration. In addition to decreasing angiotensin II and increasing bradykinin levels, ramipril increases the levels of vasodilatory renal medullary neutral lipids and inhibits platelet-derived growth factor-induced proliferation of glomerulus cells. Ramipril also decreases transforming growth factor-beta in the kidney. Changes in kidney structure and proteinuria are characteristics of the streptozotocin (STZ) rat model of diabetes, and these are prevented by ramipril. In STZ diabetes, doses of ramipril that have no effect on blood pressure reverse vascular hypertrophy. In animal models of kidney failure (subtotal nephrectomy, stroke-prone spontaneously hypertensive rats), ramipril is renoprotective and some of this renoprotective effect is independent of blood pressure lowering. In humans, clinical doses of ramipril probably do not modify glucose metabolism but do reduce the levels of LDL- and HDL-cholesterol. In clinical trials of renal effects, ramipril has been shown to increase cortical nephron flow in hypertension and to reduce proteinuria in patients with and without diabetes and/or hypertension. Some of the smaller clinical trials showed beneficial effects on kidney function with low doses of ramipril that do not lower blood pressure. A large clinical trial in nondiabetic proteinuria, the Ramipril Efficacy in Nephropathy (REIN) trial, has shown that ramipril 1.25 mg/day, which does not lower blood pressure, arrested the decline in glomerular filtration rate and prolonged the time to end-stage renal failure. In diabetic patients who have had a previous cardiovascular event or having one other cardiovascular risk factor, the MICRO-HOPE clinical trial showed that ramipril lowers the combined risk of myocardial infarction, stroke and cardiovascular death by 25%. In conclusion, ramipril has proven beneficial effects in kidney disease alone or in association with diabetes and in diabetes without kidney disease, and is the pril for diabetes and kidney disease. (c) 2001 Prous Science. All rights reserved.
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PMID:Is Ramipril the pril for diabetes and kidney disease? 1276 20

About two thirds of patients on renal replacement therapy irreversibly lose their kidney function because of progressive nephropathies, such as diabetic nephropathy and nondiabetic chronic renal disease. Halting the progression of these patients to end-stage renal disease (ESRD) is instrumental to substantially decrease the need and cost for renal replacement therapy. A large number of experimental studies have demonstrated that chronic nephropathies share common pathogenic mechanisms that contribute to renal disease progression, even independently of the original etiology. Actually, a variety of insults may result in a common pathway of systemic hypertension, increased glomerular pressure and protein ultrafiltration, glomerular and tubular protein overload, chronic inflammation and, ultimately, scarring. Experimental and clinical data converge to indicate that in chronic renal disease increased protein traffic is nephrotoxic, proteinuria predicts disease progression, and proteinuria reduction is renoprotective. Initial clinical trials, mostly in patients with no or mild proteinuria, failed to demonstrate that ACE inhibition therapy is renoprotective in nondiabetic chronic nephropathies. Consistently, meta-analyses based on data generated by these trials failed to detect a specific, blood pressure-independent, renoprotective effect of ACE inhibition therapy. The Ramipril Efficacy In Nephropathy (REIN) study found that ACE inhibitors, by reducing urinary proteins, may contribute to improve the outcome of nondiabetic renal disease, and reduce the risk of progression to ESRD by about 50%. Cumulative meta-analyses, including the REIN study results, confirmed and extended these findings. Thus, well-designed trials in properly selected and carefully monitored study populations continue to be the best approach to test the efficacy of novel treatments. The meta-analyses may help confirming the consistency of these findings and their generalizability to larger cohorts of patients.
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PMID:Proteinuria predicting outcome in renal disease: nondiabetic nephropathies (REIN). 1548 27

The objective of our study was to evaluate the changes of blood pressure (BP), urinary protein excretion (PRT/Cr) and renal function (GFR) after long-term administration of ACE inhibitor, ramipril. This prospective trial, a part of the European Multicentric Escape Study, included 14 patients (5 girls and 9 boys), mean-age 11 years, with congenital renal malformations. The basic inclusion criteria were stable chronic renal failure (CRF) and mean arterial pressure (MAP) above 50 percentile defined by 24-hour ABPM or earlier antihypertensive medication. The patients were studied 6 months before and up to 36 months after the introduction of ramipril therapy. The dosage of ramipril ranged from 4.7 to 7.7 mg/ m2 SBA, mean 37.8 (+/- 4.03) mg/m2 SBA. The patients were controlled every two months for BP, proteinuria and GFR, while 24-hour ABPM was performed in 6 months. The significant decrease of regular and 24-hour ambulatory blood pressure (ABP), systolic, diastolic and MAP, was found within the first months of treatment, while ramipril-induced reduction of proteinuria and slowing down of GFR were delayed. BP did not differ significantly among patients, but antiproteinuric effect and influence on GFR showed large individual variations. Antiproteinuric and antihypertensive effects of ramipril correlated with underlying proteinuria, GFR and blood pressure. However, there was no constant relationship between changes of proteinuria and BP. Ramipril has been shown to: lower BP significantly, decrease proteinuria slowly, and significantly decelerate GFR after 18 months of treatment. Considering favorable preliminary results of lower BP, decrease of proteinuria and decelerated GFR, an optimal renal protection by long-term therapy with ACE inhibitors may be expected in children with CRF caused by congenital renal malformations.
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PMID:[Renoprotective effect of ramipril in children with chronic renal failure--the experience of one centre]. 1561 62

A progressive chain of pathophysiological events links cardiovascular risk factors to clinical manifestations of disease and life-threatening cardiovascular events. This chain--the cardiovascular continuum--underlies cardiovascular disease and holds the key to its prevention and treatment. Progressive tissue damage can result in morbidity from congestive heart failure, end-stage heart disease, nephrotic proteinuria and dementia and, eventually, death from cardio- or cerebrovascular causes. The renin-angiotensin-aldosterone system (RAAS) is involved at all stages of the cardiovascular continuum, because the effector molecules of the RAAS, angiotensin II in particular, have direct pathobiological effects on a variety of tissues, including the endothelium, vascular smooth muscle and the renal mesangium. Clinical trials of angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors have demonstrated the essential validity of this hypothesis. Interruption of the RAAS has been shown to reduce cardiovascular morbidity and mortality in patients with left ventricular hypertrophy, heart failure and post-myocardial infarction, as well as renal disease in patients with type 2 diabetes. Key questions remain, however. What are the clinical effects of combination ARB and ACE inhibitor treatment? How will combinations of RAAS blockade with other agents, such as statins, affect the cardiovascular continuum? Answers to these questions will require well-planned, adequately powered clinical trials, such as the Programme of Research tO evaluate Telmisartan End-organ proteCTION (PROTECTION) and the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) programmes. However, it is already clear that RAAS blockade is an essential part of blocking progression along the cardiovascular continuum.
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PMID:The cardiovascular continuum and renin-angiotensin-aldosterone system blockade. 1582 52

ESRD represents a major health problem. The number of patients who enter kidney replacement programs has increased at an average of 7% per year in the past 10 yr. A large number of experimental and clinical studies have demonstrated that chronic nephropathies share common pathogenic mechanisms that contribute to renal disease progression, even independent of the original cause. Clinical studies found a significant correlation between the extent of urinary protein excretion and the rate of GFR decline in both diabetic and nondiabetic chronic nephropathies. Randomized trials, in particular the Ramipril Efficacy In Nephropathy (REIN) study, also showed that treatments that reduce proteinuria (namely angiotensin-converting enzyme [ACE] inhibitors) are renoprotective and limit progression to ESRD. Meta-analyses of randomized clinical trials also evaluated the role of proteinuria and of ACE inhibition therapy in chronic renal disease progression. Their findings were consistent with those of the REIN study and confirmed in larger series of patients the predictive value of proteinuria and the renoprotective effect of proteinuria reduction by ACE inhibition therapy. Thus, the meta-analyses may confirm and extend previous findings generated by randomized clinical trials. Conceivably, well-designed studies in properly selected and carefully monitored patients who are at increased risk continue to be the best approach to test novel hypotheses. The meta-analyses, however, represent a valuable tool to evaluate the consistency and generalizability of trial results to larger cohorts of patients.
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PMID:Angiotensin-converting enzyme inhibition and renal protection in nondiabetic patients: the data of the meta-analyses. 1593 36

The HOPE study was a 19 country, prospective randomized trial in which the ACE-inhibitor Ramipril but not Vitamin E significantly reduced the risk of future cardiovascular events in a high-risk population of men and women, including many with diabetes. The benefits were present in all sub-groups, independent of the presence or absence of diabetes, hypertension, evidence of cardiovascular disease, microalbuminuria, blood pressure lowering, the use of aspirin, lipid-lowering or antihypertensive medication. It provided clear evidence that Ramipril should safely and cost-effectively be used in individuals not known to have low ventricular ejection fraction or heart failure but at high-risk of cardiovascular events. It was also beneficial in patients with renal insufficiency, reducing progression of proteinuria and development of new microalbuminuria. It provided micro- and macrovascular benefits in people with diabetes, reduced the development of new cases of diabetes and showed a positive and graded association between the waist-to-hip ratio and the risk of developing diabetes. Sub-studies completed and on-going into the predictive role of natriuretic peptides, infectious and inflammatory markers, provide insight into possible mechanisms of action of Ramipril.
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PMID:The HOPE (Heart Outcomes Prevention Evaluation) Study and its consequences. 1611 72

Current national guidelines recommend aggressive lowering of blood pressure (< 130/80 mm Hg) in patients with chronic kidney disease (CKD). In this paper, we summarize recent clinical trial data evaluating the effect of lower blood pressure goals on renal outcomes. The epidemiologic data relating blood pressure to progression of kidney disease, the Modification of Diet in Renal Disease (MDRD) study (in patients with > 1 g proteinuria/d), and meta-analyses of angiotensin-converting enzyme (ACE) inhibitor clinical trials all support lower blood pressure goals in CKD patients, particularly those with proteinuria. The African American Study of Kidney Disease and Hypertension (AASK) supports lower blood pressure goals in terms of reduction of proteinuria, but demonstrates no additional benefit for clinical renal outcomes. Similarly, the second Ramipril Efficacy in Nephropathy study (REIN-2) shows that in patients with proteinuric nondiabetic renal disease who are receiving ACE inhibitors, a lower than usual blood pressure goal does not improve renal outcomes. However, there are limited clinical trial data evaluating the effects of low blood pressure on the increased cardiovascular risk seen in patients with CKD. Pending further clinical studies, current recommendations to target tight blood pressure control (< 130/80 mm Hg) in patients with CKD appear reasonable.
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PMID:The African American Study of Kidney Disease: do these results indicate that 140/90 mm hg is good enough? 1615 80

Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin-angiotensin system (RAS), has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB) and/or angiotensin-converting enzyme (ACE) inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) Programme is expected to provide the ultimate evidence of whether improved endothelial function translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade). Completion of ONTARGET is expected in 2008.
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PMID:Cardiovascular risk reduction by reversing endothelial dysfunction: ARBs, ACE inhibitors, or both? Expectations from the ONTARGET Trial Programme. 1758 70

Studies have shown that dual therapy with angiotensin-converting enzyme inhibitors (ACEI) and either angiotensin II receptor blockers or aldosterone receptor antagonists is more effective in reducing proteinuria than either agent used alone. The questions that remain are as follows: (1) Which of these agents should be used as dual therapy with the ACEI? (2) Does a higher level of blockade of the renin-angiotensin-aldosterone system with triple therapy offer an advantage over dual blockade? A 3-mo randomized, double-blind, placebo-controlled study was performed in 41 patients with proteinuria >1.5 g/d. Four treatment groups were compared: (1) Ramipril + spironolactone placebo + irbesartan placebo, (2) ramipril + irbesartan + spironolactone placebo, (3) ramipril + irbesartan placebo + spironolactone, and (4) ramipril + irbesartan + spironolactone. The percentage change in protein excretion differed according to treatment arm (ANOVA: F(3,35) = 8.6, P < 0.001). Pair-wise comparison showed that greater reduction in protein excretion occurred in treatment regimens that incorporated spironolactone. The reduction in proteinuria at 3 mo was as follows: Group 1, 1.4%; group 2, 15.7%; group 3, 42.0%; and group 4, 48.2%. The reduction in proteinuria among patients who were taking spironolactone-containing regimens was sustained at 6 and 12 mo. This study suggests that aldosterone receptor blockade offers a valuable adjuvant treatment when used with ACEI therapy for the reduction of proteinuria. Results suggest no advantage of triple blockade over dual blockade of the renin-angiotensin-aldosterone system to reduce proteinuria.
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PMID:Double-blind, placebo-controlled study on the effect of the aldosterone receptor antagonist spironolactone in patients who have persistent proteinuria and are on long-term angiotensin-converting enzyme inhibitor therapy, with or without an angiotensin II receptor blocker. 1769 14

Patients with kidney failure are at high risk of a cardiac death and frequently develop left ventricular hypertrophy (LVH). The mechanisms involved in the cardiac structural changes that occur in kidney failure are yet to be fully delineated. Angiotensin-converting enzyme (ACE) 2 is a newly described enzyme that is expressed in the heart and plays an important role in cardiac function. This study assessed whether ACE2 plays a role in the cardiac remodelling that occurs in experimental acute kidney injury (AKI). Sprague-Dawley rats had sham (control) or subtotal nephrectomy surgery (STNx). Control rats received vehicle (n = 10), and STNx rats received the ACE inhibitor (ACEi) ramipril, 1 mg kg(-1) day(-1) (n = 15) or vehicle (n = 13) orally for 10 days after surgery. Rats with AKI had polyuria (P < 0.001), proteinuria (P < 0.001) and hypertension (P < 0.001). Cardiac structural changes were present and characterized by LVH (P < 0.001), fibrosis (P < 0.001) and increased cardiac brain natriuretic peptide (BNP) mRNA (P < 0.01). These changes occurred in association with a significant increase in cardiac ACE2 gene expression (P < 0.01) and ACE2 activity (P < 0.05). Ramipril decreased blood pressure (P < 0.001), LVH (P < 0.001), fibrosis (P < 0.01) and BNP mRNA (P < 0.01). These changes occurred in association with inhibition of cardiac ACE (P < 0.05) and a reduction in cardiac ACE2 activity (P < 0.01). These data suggest that AKI, even at 10 days, promotes cardiac injury that is characterized by hypertrophy, fibrosis and increased cardiac ACE2. Angiotensin-converting enzyme 2, by promoting the production of the antifibrotic peptide angiotensin(1-7), may have a cardioprotective role in AKI, particularly since amelioration of adverse cardiac effects with ACE inhibition was associated with normalization of cardiac ACE2 activity.
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PMID:Acute kidney injury in the rat causes cardiac remodelling and increases angiotensin-converting enzyme 2 expression. 1822 26

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