Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite a marked reduction in cardiovascular morbidity and mortality, treated hypertensive patients remain at increased risk of coronary artery disease and its complications compared with untreated normotensive subjects. Mild hypertension is often associated with other, usually chronic, diseases. The failure of first-line antihypertensive therapy to deal adequately with concomitant disease and associated therapy might account for the poor improvement in the cardiovascular prognosis. This possibility has been addressed in an ongoing trial of novel design, the Perindopril Therapeutic Safety Study, a multicenter, double-blind, randomized and placebo-controlled trial to determine the safety, efficacy, and interaction of angiotensin-converting enzyme (ACE) inhibition with eight of the most common concomitant diseases and their therapies. A total of 480 male and female patients (60 per disease group) aged 30-70 years, with a diastolic pressure of 90-104 mm Hg, were included after a 3-week placebo run-in if they satisfied standard criteria for any of the following: hyperlipidemia, type II diabetes, ischemic heart disease, cardiac arrhythmia, peripheral arterial disease, nephropathy with proteinuria, chronic obstructive lung disease, or rheumatoid arthritis. Of these, 460 patients have completed the 6-week double-blind phase (comprising two assessments, at 3 and 6 weeks), and are currently undergoing assessments every 3 months over a 1-year follow-up period. The end points include the incidence of progression or improvement in concomitant disease, the incidence of positive or negative interaction between ACE inhibition and concomitant therapy, change in blood pressure, adverse biochemical and hemodynamic reactions, self-reported side effects, and quality of life indices. Interim results for the 6-week double blind phase will shortly be available. However, the desirability and feasibility of conducting a study according to this novel design have already been proved.
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PMID:Angiotensin-converting enzyme inhibition in mild hypertension with concomitant diseases and therapies: an efficacy, safety, and compatibility study of novel design, the Perindopril Therapeutic Safety Study. 158 Feb 90

A multicenter, double-blind, randomized, and placebo-controlled trial, the Perindopril Therapeutic Safety Study (PUTS), was designed to assess the interaction between angiotensin-converting enzyme (ACE) inhibition and the diseases and therapies commonly found associated with mild hypertension. A total of 480 male and female patients aged 30-70 years with a diastolic pressure of 90-104 mm Hg were included after a 3-week placebo run-in if they satisfied standard criteria for any of the following: hyperlipidemia, type II diabetes, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive lung disease or treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). At the end of the placebo run-in period, patients were randomly assigned to either placebo or perindopril 4 mg once daily. A total of 460 patients completed the 6-week double-blind phase, comprising 3 assessments at 1, 3, and 6 weeks. In this report, the principal results obtained in 5 disease groups (hyperlipidemia, type II diabetes, ischemic heart disease, nephropathy with proteinuria, and NSAID treatment) will be reported. A total of 269 patients belonging to one of the aforementioned 5 disease groups completed the double-blind phase of the study and were included for statistical evaluation. In the perindopril group, systolic and diastolic blood pressures decreased significantly more than in the placebo group, and a sitting diastolic blood pressure of 90 mm Hg was achieved in 65% of patients in the perindopril group and 30% of patients in the placebo group. The incidence of symptoms spontaneously reported by the patients was low: 2 patients of the perindopril group complained of cough.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A new trial of the efficacy, tolerability, and safety of angiotensin-converting enzyme inhibition in mild systemic hypertension with concomitant diseases and therapies. Perindopril Therapeutic Safety Study Group (PUTS). 832 65

In nonimmunological models of renal damage, abnormal traffic of proteins through the glomerular capillary is one of the possible causes of renal disease progression. Here we investigated whether in a model of immune-mediated glomerulonephritis long-lasting proteinuria resulted in renal structural damage and whether chronic treatment with perindopril, an angiotensin-converting enzyme (ACE) inhibitor, lowered proteinuria and retarded disease progression. Passive Heymann nephritis (PHN), a model of human membranous nephropathy, was induced with 0.5 ml/100 g of rabbit anti-Fx1 A antibody in 26 male Sprague-Dawley rats. Animals were then divided into two groups of 13 rats each, given daily vehicle or perindopril (1 mg/kg p.o). Treatment started at day 7 when proteinuria was already present and lasted 12 months. An additional group of normal rats was used as control. Renal biopsies were taken at months 8 and 12. Untreated PHN rats showed a significant increase in systolic blood pressure starting from month 8, that was normalized by perindopril administration. Urinary protein excretion progressively increased with time in untreated PHN rats that developed focal and segmental glomerulosclerosis and tubulointerstitial damage. Perindopril significantly reduced proteinuria and limited glomerular and tubulointerstitial injury. Urinary excretion of endothelin-1 (ET-1) and transforming growth factor-beta 1 (TGF-beta 1), two major mediators of renal damage in other models of glomerulonephritis, increased with time in PHN but only the former correlated with the degree of glomerulosclerosis. The effect of perindopril on proteinuria and renal structural damage was associated with a significant reduction in urinary ET-1 but not TGF-beta 1, suggesting that ET-1 may be an important determinant of disease progression in experimental membranous nephropathy.
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PMID:Passive Heymann nephritis: evidence that angiotensin-converting enzyme inhibition reduces proteinuria and retards renal structural injury. 898 42

Administration of lithium in the diet to new-born rats induces chronic renal failure associated with hypertension, proteinuria and irreversible tubulo-interstitial morphological changes. In the present study we induced chronic renal failure by administration of lithium for 16 weeks to new-born rats, and examined the spontaneous course of this nephropathy and the effects of antihypertensive treatment with either perindopril (12 mg/kg diet) or hydrochlorothiazide (500-1000 mg/kg diet) during a 24 weeks follow up period without lithium. In the placebo group, progression to terminal uraemia occurred in all rats with severe renal failure (initial Purea > 15 mM) (10 of 18). Rats with mild-moderate renal failure (Purea 9-15 mM) showed no deterioration in renal function despite persistent systolic hypertension and irreversible structural renal changes. Perindopril normalized the blood pressure in all rats but did not prevent the progression to terminal uraemia (8 to 18). Hydrochlorothiazide partially controlled the hypertension and accellerated the progression of uraemia without increasing the mortality (7 of 17). Irrespective of treatments, the predominant quantitative structural changes (e.g. decreased volume of proximal tubular cells) showed significant correlations with the degree of renal dysfunction, but not with systolic blood pressure in the surviving rats. It is concluded that progression of lithium-induced nephropathy to terminal uraemia occurs when the nephrotoxic insult results in a more than 50% reduction of the glomerular filtration rate, judged from Purea levels. The failure of effective antihypertensive treatment with an angiotension-converting enzyme inhibitor to modify the progression suggests that in this model, systemic or glomerular hypertension may not be an important pathophysiological factor. The structural and functional deterioration observed in Li-uraemic rats during treatment with hydrochlorothiazide remains unexplained.
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PMID:Effects of perindopril and hydrochlorothiazide on the long-term progression of lithium-induced chronic renal failure in rats. 910 86

Renal interstitial expansion is now considered a useful marker of progression of several nephropathies. This study describes a multicenter, prospective, double-blind, placebo-controlled, randomized trial of the effects of Perindopril (4 mg/d) on kidney structure and function over 2 yr in 26 type 2 diabetic patients with proteinuria ranging from 70 to 4210 mg/d and relatively preserved GFR (creatinine clearance >60 ml/min). All patients underwent baseline renal biopsy, but four (15%) were not randomized because of the presence of nondiabetic nephropathy. The remaining 22 were randomized ( 11 to Perindopril [PE], 11 to placebo [PO]), and 19 (9 PE, 10 PO) underwent follow-up biopsy at 2 yr. BP was controlled equally in both groups throughout. Proteinuria increased in PO patients (+1562 mg/d) but declined in PE patients (-156 mg/d) (P < 0.05). Morphometric analysis was performed by light microscopy using a Biocom computer. Over the 2 yr, mean cortical interstitial fractional volume identical at baseline increased significantly in PO patients (31.7 +/- 5.3 versus 40.2 +/- 11.1%; P = 0.001) but was unchanged in PE patients (33.8 +/- 4.9 versus 34.7 +/- 6.6%; P = 0.50). It is concluded that: (1) nondiabetic nephropathy is present in approximately 15% of albuminuric type 2 diabetic patients; and (2) Perindopril prevents interstitial expansion in hypertensive patients with biopsy-proven diabetic glomerulopathy. These results support a role of angiotensin II in the progression of interstitial changes in type 2 diabetic patients with nephropathy.
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PMID:Expansion of cortical interstitium is limited by converting enzyme inhibition in type 2 diabetic patients with glomerulosclerosis. The Diabiopsies Group. 1036 63

The angiotensin-converting enzyme inhibitor, perindopril erbumine, has been approved for use in the United States only recently but has been studied extensively worldwide over the last decade. Placebo-controlled trials in a wide range of patients with hypertension, including the elderly, those with isolated systolic hypertension, and those with concomitant diseases such as hyperlipidemia, diabetes, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, and chronic obstructive pulmonary disease, have shown that perindopril is highly effective in lowering both systolic and diastolic blood pressure (BP). Studies in which BP has been monitored for 24-hour intervals show that perindopril (1) has a gradual onset of action, (2) provides smooth BP control over its once-daily dosing interval, (3) has a trough-peak ratio of about 1, and (4) maintains its antihypertensive efficacy despite missed doses. Perindopril increases arterial compliance and reverses left ventricular hypertrophy in hypertensive patients. Both of these effects are at least partly independent of its ability to lower BP. Perindopril is safe and well tolerated in patients with hypertension. Rates of adverse events and discontinuation because of such events are low.
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PMID:Efficacy of perindopril in the treatment of systemic hypertension. 1159 55

Approximately 25% of US adults have high blood pressure (BP). Selection of effective and safe antihypertensive therapy for these individuals is an important health-care priority. High BP can be treated with a wide range of antihypertensive agents from a number of different classes. These drugs may differ in their suitability for administration to different subpopulations of patients. Results from both clinical trials and postmarketing surveillance indicate that the angiotensin-converting enzyme (ACE) inhibitor perindopril erbumine is safe and well tolerated in a wide range of patients with hypertension. Cough, the most common ACE inhibitor-associated side effect, is also the most common clinical adverse event reported for perindopril, but <2% of perindopril-treated patients discontinue therapy because of cough. Other adverse events often associated with ACE inhibitors, first-dose hypotension and hyperkalemia, appear to occur less often with perindopril than with other agents in this class. The favorable safety profile for perindopril extends to a wide range of patients, including the elderly and those with either heart failure or renal disease. Perindopril has no negative effects on lipids in patients with hyperlipidemia or on glycemic control in patients with type 2 diabetes mellitus, and it reduces proteinuria in patients with renal disease. Perindopril has no known clinically significant drug-drug interactions. Thus, perindopril is a safe BP-lowering agent with documented tolerability in a wide range of patients with hypertension.
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PMID:Safety profile of perindopril. 1159 59

Angiotensin II type-1 receptor blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEI) have been thought to be effective for reducing proteinuria in patients with chronic glomerulonephritis. Recently, an additive effect of these two types of angiotensin blockers has been reported in patients with IgA nephropathy, but the mechanism responsible for the effect has not yet been determined. In this study, we examined additive effect of these two drugs in chronic glomerulonephritis patients. Ten patients with biopsy-proven primary glomerulonephritis (eight IgA nephropathy patients, two membranous nephropathy patients), non-nephrotic proteinuria (protein, 0.5 to 3.5 g/day) received candesartan cilexetil (2 or 4 mg) for 8 weeks. After the 8 weeks, a combination of perindopril erbumine (1 or 2 mg) and candesartan cilexetil was administered to the patients. Perindopril was stopped after the 8-week administration of the two drugs. Candesartan alone reduced proteinuria by 13%. Combination of these two drugs induced a more remarkable reduction of proteinuria (48%; p < 0.05 vs other periods). The decrease in mean blood pressure by the combination therapy was significantly correlated with the decrease in proteinuria. The combination of drugs also reduced the amount of urinary type-IV collagen excretion. An additive effect of ACEI and ARB on proteinuria and urinary type-IV collagen excretion was recognized in patients with chronic glomerulonephritis.
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PMID:[Additive antiproteinuric effect of angiotensin II receptor antagonist and angiotensin-converting enzyme inhibitor in patients with chronic glomerulonephritis]. 1450 19

The role of angiotensin-converting enzyme (ACE) inhibitors in diabetic patients with preserved ventricular function is uncertain. Tissue ACE inhibitors have been defined by increased lipophilicity and structural characteristics that result in greater tissue-specific ACE binding when compared with plasma ACE inhibitors. A Bayesian meta-analysis of randomized trials was conducted to evaluate tissue ACE inhibitors in prevention of cardiovascular disease among patients with diabetes mellitus and preserved left ventricular function. Four trials were selected that evaluated 2 different ACE inhibitors and included 10,328 patients (43,517 patient-years). The Perindopril Substudy in Coronary Artery Disease and Diabetes (PERSUADE) and the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) compared the effects of perindopril vs a placebo, and the Heart Outcomes Prevention Evaluation (HOPE) and the Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study investigated the impact of ramipril vs a placebo. Bayesian meta-analysis of sequential trials and sensitivity analysis of therapeutic response were subsequently computed. Bayesian meta-analysis determined reduced risk of cardiovascular mortality (PB=.991), myocardial infarction (PB=.999), and the need for invasive coronary revascularization (PB=.995) when compared with placebo. Total mortality was also decreased (PB=.967), while the risk of stroke (PB=.907) and hospitalization for heart failure (PB=.923) were impacted. Bayesian meta-analysis of randomized trials suggests that tissue ACE inhibitors decrease the probability that diabetic patients with preserved left ventricular function will experience myocardial infarctions and cardiovascular death and reduce overall mortality.
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PMID:Bayesian meta-analysis of tissue angiotensin-converting enzyme inhibitors for reduction of adverse cardiovascular events in patients with diabetes mellitus and preserved left ventricular function. 1832 70