Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is an important risk factor for vascular disease. Primary goal of hypertension treatment is to prevent or delay the onset of blood pressure-related morbidity and mortality. It has been well demonstrated that the responses rate to any single class of antihypertensive agent, give as monotherapy is approximately 45% to 55%, and in half of hypertensive population a second will be required. The data from clinical trials clearly demonstrate that two-drug combination, usually with low-dose diuretics with any one of the other first-line agents increases the response rate to about 80% to 85% and reduces the likelihood of adverse events and alteration in lipid, carbohydrate and electrolyte metabolism. Of the various combinations being given that of an diuretic and ACE inhibitor, and ACE inhibitor and non-dihydropyridine calcium channel blockers seems particularly attractive. Some combinations are inappropriate, such as diuretic and calcium channel blockers, and beta-blocker with verapamil and diltiazem. Combination of ACE inhibitor and a non-dihydropyridine calcium channel blockers may provide benefit in regression left ventricular hypertrophy diabetic nephropathy, and post myocardial infarction.
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PMID:[Combination therapy in primary hypertension]. 955 8

Between 1988 and 1992, 565 type 2 diabetic patients were examined for nephropathy and diabetes-associated diseases during hospital treatment. Stages of nephropathy were defined as no clinical sign of nephropathy (N = 280), microalbuminuria (N = 38), overt proteinuria (N = 105), impaired renal function (N = 55), and chronic dialysis therapy (N = 87). In dialyzed patients, HbA1c averaged 6.8%, and, in the other groups, HbA1c was between 7.6% and 8.3% (normal range, 3.8%-6.1%). Cataract was not associated with the severity of nephropathy. Stroke was most common in the stage of renal insufficiency (34%). The following complications, as found in medical history or as current event, showed a significant association with the stage of nephropathy and occurred most frequently in dialysis patients (percentage is displayed for patients with nephropathy in comparison to diabetic dialysis patients): hypertension (53%-89%), left ventricular hypertrophy (39%-81%), myocardial infarction (14%-36%), peripheral vascular disease (27%-77%), foot lesions (7%-75%), minor or major amputations (3%-23%), proliferative retinopathy (6%-46%), blindness (2.9%-16.1%), and internal carotid artery stenosis (15%-36%). In this preselected cohort of diabetic patients, a high morbidity was found already without nephropathy that increased several-fold in the course of the development of nephropathy. Our data identify patients with diabetic nephropathy as a high-risk group for excess morbidity.
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PMID:Morbidity in 565 type 2 diabetic patients according to stage of nephropathy. 955 88

ACE inhibitors have achieved widespread usage in the treatment of cardiovascular and renal disease. ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and hypertrophic properties of angiotensin II (Ang II) and the vasodilatory and natriuretic properties of bradykinin and alter the metabolism of a number of other vasoactive substances. ACE inhibitors differ in the chemical structure of their active moieties, in potency, in bioavailability, in plasma half-life, in route of elimination, in their distribution and affinity for tissue-bound ACE, and in whether they are administered as prodrugs. Thus, the side effects of ACE inhibitors can be divided into those that are class specific and those that relate to specific agents. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have proved effective in the treatment of hypertension, they decrease mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction, and they delay the progression of diabetic nephropathy. Ongoing studies will elucidate the effect of ACE inhibitors on cardiovascular mortality in essential hypertension, the role of ACE inhibitors in patients without ventricular dysfunction after myocardial infarction, and the role of ACE inhibitors compared with newly available angiotensin AT1 receptor antagonists.
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PMID:Angiotensin-converting enzyme inhibitors. 957 53

The renin-angiotensin system is central to the pathophysiology of a number of cardiovascular disorders. Most obviously this is so with renin secreting tumours, but the system is of central importance in other disorders such as scleroderma renal crisis and most cases of malignant hypertension. Activation of the renin-angiotensin system in unilateral renal artery stenosis is pivotal to the development of hypertension and the disturbances in electrolyte and volume balance -- most particularly in the hyponatraemic-hypertensive syndrome. Likewise, stimulation of the renin-angiotensin system is an important contributor, amongst many other systems, to the pathophysiology of cardiac failure. In diabetic nephropathy, the renin-angiotensin system is often suppressed as gauged by circulating levels of renin, yet it appears to make an important contribution to the progressive decline in renal function. Much less clear is the role of the renin-angiotensin system in essential hypertension insofar as it contributes to the level of blood pressure, to the development of left ventricular hypertrophy, and in the evolution of complications such as stroke and myocardial infarction. Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors has contributed to our understanding of the role of this system in cardiovascular disease. The advent of selective angiotensin II type-1 receptor blockers will further increase knowledge in this area.
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PMID:The importance of the renin-angiotensin system in cardiovascular disease. 965 50

This manuscript will highlight the major elements of the recently published sixth Joint National Committee (JNC-6) report. First, a 3-tiered classification of overall cardiovascular risk is provided as a guide to the institution of therapy with either lifestyle modifications or antihypertensive drugs. Second, the need for prevention is stressed. Third, guidelines for the effective use of appropriate lifestyle modifications are provided. Fourth, a 3-pronged pathway for the choice of critical therapy is provided: one for uncomplicated hypertensive; another for those with "compelling" indications for specific drugs, including the presence of diabetic nephropathy, congestive heart failure, post-myocardial infarction or systolic hypertension in the elderly; the third for those with concomitant conditions that may be either favorably or unfavorably affected by specific types of drugs. In addition, the report emphasizes the need to achieve the goal of less than 140/90 mmHg by a progressive process of therapy and, if necessary, referral to a hypertension specialist. Recommendations are made for improved adherence to therapy, therapy of resistant hypertension and hypertensive crises.
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PMID:The 6th joint national committee report (JNC-6): new guidelines for hypertension therapy from the USA. 965 20

Hypertension and diabetes mellitus are both common conditions associated with a high morbidity and mortality. When the two conditions occur together, as they do in 50% of diabetic individuals, the result is a 7.2-fold increase in mortality. If hypertension occurs in association with diabetes mellitus and diabetic nephropathy, mortality rises to 37-fold above that of a healthy population. Despite the increase in incidence of nephropathy, cardiovascular disease remains the major cause of death in diabetic individuals. Therapy should therefore take into consideration the results of large, placebo-controlled trials which have shown reduction in cardiovascular morbidity and mortality as a result of active treatment. Although studies with the newer antihypertensive agents such as calcium antagonists and angiotensin converting enzyme (ACE) inhibitors are ongoing, only diuretics and beta-adrenoceptor antagonists have been clearly shown to reduce cardiovascular risk. Despite concerns regarding adverse metabolic effects and loss of hypoglycaemic awareness, beta-blockers and diuretics do have a role in the management of diabetic patients. While it is clear that ACE inhibitors reduce the progression of diabetic nephropathy, evidence suggests that diuretics may be just as effective. However, unlike diuretics or beta-blockers, ACE inhibitors have no proven benefit in the prevention of stroke of myocardial infarction. Despite the claims of metabolic neutrality made for many antihypertensive agents there appears to be no advantage in their use in the majority of hypertensive diabetic patients, except where there exist specific contraindications to established therapies.
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PMID:Drug treatment of hypertension complicating diabetes mellitus. 971 44

The angiotensin I-converting enzyme (kininase II, ACE) is the major angiotensin II forming and kinin degrading enzyme in the circulation, and has other physiological peptide substrates. Recent studies have established that the interindividual variability in the levels of ACE in plasma and tissues is under the influence of a genetic polymorphism. The genetic polymorphism of ACE levels has been linked in case-control studies to the susceptibility of developing cardiovascular diseases, especially myocardial infarction and diabetic nephropathy, and to the risk of progression of renal diseases. The new concept that the level of ACE in peripheral circulations and tissue interstitium is an important factor in the determinism of the local concentration of peptides and their putative protective/deleterious effects, especially in the kidney and the heart, will be further appraised.
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PMID:Angiotensin I-converting enzyme (kininase II) in cardiovascular and renal regulations and diseases. 983 May 3

Since the discovery at the end of the seventies of angiotensin converting enzyme inhibitors (ACEI), numerous clinical data became available in the indications for which these agents were initialy developed, taking into account the putative role of renin angiotensin system: first in severe hypertension, secondly in moderate hypertension and then in heart failure. At the same time, an increasing interest was raised for "evidence based medicine" leading to a change in clinical study design: from clinical documentation of effects based on intermediate end points such as blood pressure, serum lipids, serum electrolytes or physical training capabilities to clear demonstrations through double blind placebo controlled trial with a positive effect on morbi-mortality. This evolution was furthermore stimulated by advances of knowledge on physiopathological mechanisms as well as the emergence of new drugs within this therapeutic class both stimulating clinical research. In that prospective, three examples are obvious: treatment of myocardial infarction, slowing down of the progression of diabetic nephropathy and of chronic renal failure. All these new indications for ACEI were obtained though large morbi-mortality clinical studies which are reviewed in this article. Finally, clinical studies are running with ACEI in order to demonstrate a possible effect on primary or secondary prevention of cardiovascular morbi-mortality in high risk populations results which should be available at the beginning of the next century.
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PMID:[Conversion enzyme inhibitors against the progression of renal and vascular diseases: yes but again]. 985 84

Interest in evidence-based medicine is increasing greatly, with the focus on treatment that prevents organ failure and that may prolong life. Type 1 and Type 2 diabetes are conditions associated with increased mortality, mainly as a result of renal and cardiovascular diseases, and blindness. All three complications usually occur together. In recent years, more focus has been placed on treating patients early to prevent future organ damage. Microalbuminuria is an important intermediary end-point that correlates strongly with future advanced renal disease, retinopathy and mortality. Several trials have studied patients with microalbuminuria and also patients in more advanced stages of the disease who have proteinuria (termed overt nephropathy). Recent evidence indicates that achieving optimal glycaemic control reduces the risk of an increase in urinary albumin excretion before the development of microalbuminuria. Angiotensin-converting enzyme (ACE) inhibitors are effective in reducing microalbuminuria, partly independent of their blood pressure reducing effects. In Type 1 and Type 2 diabetic patients with microalbuminuria, long-term treatment with ACE inhibitors (7-8 years) prevents the predicted decrease in glomerular filtration rate (GFR); optimal glycaemic control is also important in preventing the decline in GFR. This is important because GFR is usually well preserved in Type 1 and Type 2 diabetic patients with microalbuminuria and a predicted decline in GFR can therefore be prevented. In overt renal disease, studies that focused mostly on Type 1 diabetic patients have shown that the rate of decline in GFR can be reduced. Long-term studies in Type 1 diabetic patients have also demonstrated that mortality caused by end-stage renal disease can be postponed. Mortality associated with cardiovascular diseases, e.g. myocardial infarction, is reduced more effectively in diabetic patients treated with ACE inhibitors and beta-blockers than in non-diabetic patients treated with the same drugs. Screening for microalbuminuria, the attainment of optimal glycaemic control, and early treatment with ACE inhibitors and other antihypertensive drugs are necessary to prevent progression of diabetic complications, especially diabetic nephropathy. However, there is some controversy about the initial use of calcium channel blockers. In conclusion, early achievement of improved glycaemic control is the most important factor in the prevention of diabetic complications. Antihypertensive treatment is clearly also important.
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PMID:Preventing end-stage renal disease. 986 93

Angiotensin-converting enzyme (ACE) inhibitors have been in clinical use for 20 years, during which time their application has been extended from the treatment of hypertension and heart failure to left ventricular dysfunction after myocardial infarction. They are also being used today for the treatment of diabetic nephropathy. More recently, the rationale for an antiatherosclerotic effect of ACE inhibition has emerged, based on more detailed understanding of the renin-angiotensin-aldosterone system and the role of this system in atherogenesis, in addition to supportive experimental animal and preliminary clinical data. The possible clinical benefit of ACE inhibition in atherosclerosis is currently being assessed in several large-scale trials with both surrogate and clinical outcome measures in high-risk patients with clinically manifest atherosclerosis, principally coronary artery disease. The trials should further elucidate the mechanisms of benefit from ACE inhibition and further define their role in therapy of patients with coronary disease.
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PMID:Towards 2001: will ACE inhibitors have a role in atherosclerosis treatment? 992 42


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