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)

Whether any class of antihypertensive drugs has specific renoprotective effects above and beyond lowering of blood pressure is still debatable. The renin-angiotensin system (RAS) is both localized and has many actions within the kidney, on intrarenal hemodynamics, on the mesangial cell, as well as stimulating growth factors and cytokines. Angiotensin converting enzyme (ACE) inhibitors have been shown to ameliorate the progression of renal failure. How much of this beneficial effect is due to their hemodynamic effects, how much to non-hemodynamic effects and how much to their effects on bradykinin and other putative ACE substrates is still unclear. Experimentally it can be shown that inhibiting ACE but preventing the fall in systemic blood pressure by salt loading abolishes renoprotection. Bradykinin has been implicated in both the beneficial and the adverse effects of ACE inhibitors. Because of this and because ACE inhibitors may not provide complete blockade of the RAS, angiotensin receptor (AT1R) antagonists have been developed. Experimentally AT1R antagonists have been shown to reproduce most of the beneficial effects of ACE inhibitors. The experience in humans is more limited but they have been demonstrated to be efficacious in hypertension, to reduce proteinuria, and produce a favorable hemodynamic effect in congestive cardiac failure with a low incidence of adverse effects and without cough. Calcium channel blockers (CCB) also have additional properties that may provide renoprotection beyond lowering blood pressure. However, as the different types of CCB block different calcium channels their effects may differ substantially. The inconsistency of the data in the renoprotective effect of CCB may reflect these differences. Quantitatively probably the most important factor in preventing the progress of renal failure by antihypertensive drugs is strict control of blood pressure. Lowering blood pressure by drugs is most likely effective by both reducing physical and sheer stress damage, as well as turning off the signal for the activation and production of vasoactive peptides and cytokines.
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PMID:Comparison of renin-angiotensin to calcium channel blockade in renal disease. 940 14

Prognosis of systemic sclerosis (scleroderma, Ssc) is largely depending on involvement of internal organs. Abnormalities of the gastrointestinal tract are found most frequently (85%), especially decreased motility of the oesophagus, which has little impact on the longterm clinical course of Ssc. Pulmonary manifestations can be demonstrated in 40-90% of patients; one must distinguish between pulmonary hypertension or fibrotic lung disease. The heart is affected in 50% of cases. Patchy or diffuse myocardial fibrosis, as well as pericarditis and pericardial effusions can induce symptoms of arrhythmia or congestive heart failure. Renal involvement is associated with increased mortality and occurs in 45% of Ssc, producing proteinuria, hypertension, scleroderma renal crisis and renal failure. In conclusion, involvement of the lungs, heart and kidneys are determining factors for the longterm course of systemic sclerosis.
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PMID:[Progressive systemic scleroderma--prognosis determining involvement of internal organ systems]. 971 81

A 29-year-old nulliparous woman had development of hypertension, proteinuria, and congestive heart failure during the third trimester of her pregnancy. Her symptoms and cardiovascular changes were consistent with congestive heart failure and severe preeclampsia. The underlying pathophysiology was believed to be caused by the high-output state of pregnancy and by the increased peripheral vascular resistance of preeclampsia. The patient underwent an elective cesarean section, but her cardiovascular symptoms did not resolve. Soon after delivery, the patient was found to have an arteriovenous fistula of the right renal artery that caused the high-output cardiac state. Embolization and surgical removal of the arteriovenous fistula resulted in complete resolution of the patient's high-output heart failure. All previously reported cases of renal arteriovenous fistulas and malformations that have occurred during pregnancy are reviewed.
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PMID:High-output heart failure due to a renal arteriovenous fistula in a pregnant woman with suspected preeclampsia. 973 27

Essential hypertension is a major Public Health issue. Although the number of treated hypertensive patients has increased, only 25% of treated patients have their blood pressure levels under control. The benefit of treating hypertension has been proven, but cardiovascular morbidity and mortality rates remain high. The ideal antihypertensive drug should not only normalize blood pressure levels, but also reduce the associated cardiovascular morbidity and mortality rates. The role of angiotensin II in systemic hypertension and its complications has been recently redefined. The potent trophic effects of angiotensin II on blood vessels and on cardiac cells have been well demonstrated, especially the role of angiotensin II in left ventricular hypertrophy, vascular hypertrophy, endothelial dysfunction, and congestive heart failure. Of all ongoing mortality and morbidity trials in systemic hypertension, VALUE (Valsartan Antihypertensive Long-term Use Evaluation) is the only one comparing an angiotensin II antagonist (valsartan) with a third-generation calcium channel blocker (amlodipine). The main hypothesis of the VALUE trial is that, for an equivalent decrease in blood pressure, valsartan will be more effective than amlodipine in decreasing cardiac mortality and morbidity. VALUE is a prospective, multinational, multicentre, double-blind, randomized, active-controlled, 2-arm parallel group comparison with a response-dependent dose titration scheme. VALUE involves 14,400 patients in over 30 countries, who will be followed for 4 years or until 1450 patients experience a primary endpoint. The population to be included in VALUE consists of hypertensive men and women, aged 50 years or older, and at a relatively high risk of sustaining a cardiovascular event. The high risk profile is defined taking into account age, gender, and a list of cardiovascular risk factors and disease factors. Risk factors are cigarette smoking, hypercholesterolaemia, diabetes mellitus, uncomplicated left ventricular hypertrophy, proteinuria, and high serum creatinine. Disease factors include documented history of myocardial infarction, peripheral vascular disease, stroke or transient ischaemic attack, or the presence of left ventricular hypertrophy with strain on the ECG. A unique feature of VALUE is the assessment of the predictive power of this cardiovascular risk factor scale in a large population of treated hypertensive patients. The trial started on 10 September 1997.
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PMID:The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial of cardiovascular events in hypertension. Rationale and design. 975 88

A 77-year-old woman complaining of anorexia and nausea was referred to the hospital with a diagnosis of advanced gastric cancer. The patient also had congestive heart failure with atrial fibrillation and severe hypoproteinemia. Proteinuria, hypoproteinemia and other laboratory data suggested that she had nephrotic syndrome. Total protein level was 4.6 g/dl and albumin level was 1.6 g/dl. In order to avoid postoperative complications such as wound dehiscence, anastomotic leakage and so on, careful pre- and post-operative management of nephrotic syndrome is necessary. Administration of albumin and fresh frozen plasma regimen was continued after the operation. Urinary protein level started to decrease after subtotal gastrectomy. Histological examination revealed moderately differentiated tubular adenocarcinoma with nodal metastases. Her post-operative course was uneventful. Although the signs and symptoms of nephrotic syndrome did not improve immediately, twelve months after operation she has become well and has no symptoms of ascites and hypoproteinemia.
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PMID:A case of gastric cancer with nephrotic syndrome. 978

Verapamil sustained-release (SR)/trandolapril is a combination of a phenylalkylamine calcium antagonist and an angiotensin converting enzyme inhibitor for the management of essential hypertension. Verapamil SR/trandolapril does not adversely influence glucose, insulin or lipid parameters in patients with mild to moderate essential hypertension and type 2 (non-insulin-dependent) diabetes mellitus with or without elevated cholesterol and/or triglyceride levels. Verapamil SR/trandolapril reduces proteinuria to a greater extent than the individual components in patients with diabetic or non-diabetic proteinuria. The antihypertensive efficacy of once daily verapamil SR/trandolapril (180/1 or 180/2 mg) for 8 weeks or 6 months is similar to that of atenolol/chlorthalidone (100/25 mg) and lisinopril/hydrochlorothiazide (20/12.5 mg), and was at least as good as that of metoprolol/hydrochlorothiazide (100/12.5 mg) in a small trial. The reduction in sitting or supine diastolic and systolic blood pressure is greater after verapamil SR/trandolapril (180/2 to 240/4 mg) than after monotherapy with verapamil SR (180 and 240 mg/day) or trandolapril (2 to 8 mg/day). Fewer cardiac events occurred after verapamil SR/trandolapril (240/1 to 360/2 mg/day) than after trandolapril (1 to 2 mg/day) in postmyocardial infarction patients with congestive heart failure. The incidence of adverse events after verapamil SR/trandolapril is similar to that of comparator drugs and the individual components of the combination.
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PMID:Fixed combination verapamil SR/trandolapril. 982 57

The advent of the ACE inhibitors has been one of the major developments in cardiovascular pharmacology this century. Aside from their role as potent anti-hypertensive drugs with few adverse effects, ACE inhibitors have numerous other effects that have only been partially explained. Antihypertensive therapy is the most effective treatment in patients with diabetic nephropathy, postponing the development of end-stage renal failure. Although this effect can apparently be obtained with all antihypertensives (except nifedipine), recent meta-analyses have indicated that the beneficial effects of ACE inhibitors on proteinuria and preserved renal function are greater than with other drugs. In nondiabetic patients, treatment with ACE inhibitors may delay or prevent the development of congestive heart failure following acute myocardial infarction. Whether this also occurs in diabetic patients is still unknown, but subgroup analysis of existing studies and controlled clinical trials in this area should be encouraged. In conclusion, ACE inhibitors are the only drugs that have been proven, in controlled clinical trials, to be effective in preventing progression from micro-albuminuria to overt nephropathy. Furthermore, they are more effective in diminishing albuminuria at low levels of blood pressure reduction compared with other antihypertensives. In comparison with beta-blockers, ACE inhibitors have the advantage that they do not mask the subjective symptoms of hypoglycaemia, nor do they affect the serum lipid profile.
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PMID:ACE inhibitors in patients with diabetes mellitus. Clinical and economic considerations. 1016 Feb 52

The awareness, treatment, and control of hypertension has risen steadily over the past three decades, until the early 1990s. However, blood pressure control to < 140/90 mmHg is attained in fewer than 25% of all hypertensive patients and fewer than 50% of drug-treated hypertensive patients, except for white women. Two special populations, African-Americans and diabetics, share several important attributes. First, they both have a high prevalence of hypertension, including stage 3 hypertension (as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of Hypertension VI: > or =180/110 mmHg), relative to other subgroups. African-Americans have an approximate 8% prevalence of stage 3 hypertension, and elevated systolic blood pressure is highly prevalent among diabetic people, particularly older African-American women. Second, both groups have high levels of blood-pressure-related target-organ damage, which contributes to their inordinately high absolute risk for cardiovascular disease complications (i.e. stroke, congestive heart failure, renal failure) at a given level of blood pressure. Moreover, the reduced natriuretic capacity common to each group contributes to the attenuated efficacy of antihypertensive drug monotherapy, particularly for drug classes other than diuretics and calcium antagonists. These two special populations are also typically salt-sensitive, an intermediate blood pressure phenotype that raises blood pressure medication requirements. This phenomenon has been associated with an attenuation in the normal nocturnal fall in blood pressure. The high absolute risk for cardiovascular disease among diabetics led to the formulation of more aggressive treatment recommendations for antihypertensive drug therapy. In diabetics, blood pressure therapy is initiated at blood pressures > or = 130/85 mmHg, and treatment goals are at least to this level, unless proteinuria is > or = 1g/day (in which case the goals are < 125/75 mmHg). The more aggressive treatment targets for diabetics will not be reached with most currently available single antihypertensive agents in many African-Americans. While at best only 50-60% of hypertensive patients can be controlled with single drug therapy, that percentage falls dramatically in persons with stage 3 hypertension and renal insufficiency, thereby necessitating the use of combination drug therapy. Treatment alone is not enough; treatment to goal blood pressure is an essential first step towards optimal target-organ protection. While circulating levels of renin are suppressed, in general, in these special populations, each group manifests an inordinate burden of blood-pressure-related target-organ damage that has been linked to excessive levels of angiotensin II or a reduced bradykinin and nitric oxide tissue effect. The renin-angiotensin-aldo-sterone-kinin system is therefore an attractive therapeutic target that might conceivably provide target-organ protection over and above that attributable solely to lowering the blood pressure.
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PMID:Difficult-to-treat hypertensive populations: focus on African-Americans and people with type 2 diabetes. 1034 Aug 40

Angiotensin-converting enzyme inhibitors (ACEi) are a class of antihypertensive agents that decrease mortality in congestive heart failure and have established efficacy in the treatment of hypertension and the slowing of established diabetic nephropathy and other proteinuria-associated glomerulonephritides. These drugs have not gained wide acceptance in the treatment of hypertension in renal transplant recipients (RTRs) because of a potential for decreased renal blood flow and glomerular filtration rate associated with a single kidney and concomitant cyclosporine use. Experimental animal models suggest that ACEi may be of benefit in slowing the progression of chronic renal allograft rejection. We undertook a retrospective chart analysis of all RTRs in our institution who had been treated with an ACEi or an angiotensin II (AT II) antagonist, with the objectives of determining the safety, efficacy, and side effect profile of these medications. The minimum follow-up period was 6 months. One hundred seventy-seven of 642 RTRs were prescribed an ACEi or AT II antagonist. Forty-seven patients discontinued therapy, with the most common causes of discontinuation being cough (8 patients) and hyperkalemia (6 patients). The mean arterial blood pressure at each follow-up period was lower than that at the time of initiation of ACEi or AT II antagonist therapy, with a decrease from 92 +/- 12 mm Hg to 86 +/- 9 mm Hg (P < 0.05) after 3 years of treatment. The serum creatinine concentrations did not change throughout the follow-up period. There was a nonsustained increase from the baseline serum potassium of 4.4 +/- 0.5 to 4.6 +/- 0.6 mEq/L at 3 months (P < 0.05), but no further increases in potassium beyond this time. The mean hemoglobin concentration for the cohort did not change, but 13 RTRs given an ACEi for posttransplantation erythrocytosis (PTE) had a decrease in hemoglobin from 17.1 +/- 1.0 g/dL at the start of ACEi therapy to 14.8 +/- 2.2 g/dL at 3 years (P < 0.05). ACEi and AT II antagonists were generally effective antihypertensives, and were safe and well-tolerated agents in this cohort of RTRs. ACEi were also effective in the treatment of PTE.
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PMID:ACE inhibitors and angiotensin II antagonists in renal transplantation: an analysis of safety and efficacy. 1062 May 59

The non-insulin-dependent DIABetes, HYpertension, microalbuminuria or proteinuria, CARdiovascular events, and Ramipril (DIABHYCAR) study is a randomized, prospective, double-blind, placebo-controlled, multicenter international trial of the ACE inhibitor ramipril (1.25 mg/day) in patients with type II diabetes and micro- or macroalbuminuria. The main outcome of the study is the time to first occurrence of either death from a cardiovascular origin, including sudden death, nonfatal myocardial infarction, stroke, or congestive heart failure, or requirement of hemodialysis or renal transplantation. The study was launched in France in early 1995 with the participation of general practitioners only, but had to be extended to 15 other countries in 1997 due to difficulties in recruitment. Since 2.5 years after the beginning of the trial the observed event rate was much less than anticipated, it was decided to increase recruitment and follow-up duration and to include congestive heart failure in the definition of the main outcome to keep the study power at a satisfactory level. Recruitment ended on April 1, 1998 with 4937 randomized patients. Following the early discontinuation for efficacy of another study of ramipril in high cardiovascular risk patients, the Heart Outcomes Prevention Evaluation study (HOPE), the second interim analysis of DIABHYCAR was performed early (when 406 instead of 500 patients presented a main outcome) and the Data Safety and Monitoring Board recommended that the study continue. Follow-up is planned to end on March 31, 2001.
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PMID:The non-insulin-dependent diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events, and ramipril (DIABHYCAR) study: design, organization, and patient recruitment. DIABHYCAR Study Group. 1091 14


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