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)

The renin-angiotensin-aldosterone system (RAAS) plays an important role in both the short-term and long-term regulation of arterial blood pressure, and fluid and electrolyte balance. The RAAS is a dual hormone system, serving as both a circulating and a local tissue hormone system (i.e., local mediator) as well as neurotransmitter or neuromediator functions in CNS. Control of blood pressure by the RAAS is exerted through multiple actions of angiotensin II, a small peptide which is a potent vasoconstrictor hormone implicated in the genesis and maintenance of hypertension. Hypertension is a primary risk factor associated with cardiovascular, cerebral and renal vascular disease. One of the approaches to the treatment of hypertension, which may be considered as a major scientific advancement, involves the use of drugs affecting the RAAS. Pharmacological interruption of the RAAS was initially employed in the late 1970s with the advent of the angiotensin converting enzyme (ACE) inhibitor, captopril. ACE inhibitors have since gained widespread use in the treatment of mild to moderate hypertension, congestive heart failure, myocardial infarction, and diabetic nephropathy. As the roles of the RAAS in the pathophysiology of several diseases was explored, so did the realization of the importance of inhibiting the actions of angiotensin II. Although ACE inhibitors are well tolerated, they are also involved in the activation of bradykinin, enkephalins, and other biologically active peptides. These actions result in adverse effects such as cough, increased bronchial reactivity, and angioedema. Thus, the goal of achieving a more specific blockade of the effects of angiotensin II than is possible with ACE inhibition. The introduction of the nonpeptide angiotensin II receptor antagonist losartan in 1995 marked the achievement of this objective and has opened new vistas in understanding and controlling the additional biological effects of angiotensin II. Complementary investigations into the cloning and sequencing of angiotensin II receptors have demonstrated the existence of a family of angiotensin II receptor subtypes. Two major types of angiotensin II receptors have been identified in humans. The type 1 receptor (AT1) mediates most known effects of angiotensin II. The type 2 receptor (AT2), for which no precise function was known in the past, has gained importance recently and new mechanisms of intracellular signalling have been proposed. This review presents recent advances in angiotensin II receptor pharmacology, molecular biology, and signal transduction, with particular reference to the AT1 receptor. Excellent reviews have appeared recently on this subject.
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PMID:Angiotensin II receptors-antagonists, molecular biology, and signal transduction. 1009 99

Prophylactic coronary revascularization may reduce the risk for cardiac events in diabetic renal transplant candidates. No published data exist on the accuracy of dobutamine stress echocardiography (DSE) for the diagnosis of angiographically defined coronary artery disease (CAD) in renal transplant candidates. The purpose of this study is to examine the accuracy of DSE for the detection of CAD in high-risk renal transplant candidates compared with coronary angiography. Fifty renal transplant candidates with diabetic nephropathy (39 patients) or end-stage renal disease (ESRD) from other causes (11 patients) underwent prospectively performed DSE, followed by quantitative coronary angiography (QCA) and qualitative visual assessment of CAD severity. Twenty of 50 DSE tests were positive for inducible ischemia. Twenty-seven patients (54%) had a stenosis of 50% or greater by QCA, 12 patients (24%) had a stenosis of greater than 70% by QCA, and 16 patients (32%) had a stenosis greater than 75% by visual estimation. The sensitivity and specificity of DSE for CAD diagnosis were respectively 52% and 74% compared with QCA stenosis of 50% or greater, 75% and 71% compared with QCA stenosis greater than 70%, and 75% and 76% for stenosis greater than 75% by visual estimate. On long-term follow-up (22.5 +/- 10.1 months), 6 of 30 patients (20%) with negative DSE results and 11 of 20 patients (55%) with positive DSE results had a cardiac death, myocardial infarction (MI), or coronary revascularization. Six of 27 patients (22%) with a QCA stenosis of 50% or greater had a cardiac death or MI compared with none of the 23 patients (0%) with QCA stenosis less than 50% (P = 0.025). We conclude that DSE is a useful but imperfect screening test for angiographically defined CAD in renal transplant candidates.
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PMID:Dobutamine stress echocardiography for the detection of significant coronary artery disease in renal transplant candidates. 1035 96

Inhibitors of angiotensin converting enzyme (ACE inhibitors) have been introduced more than fifteen years ago into the treatment of hypertension, congestive heart failure, myocardial infarction and diabetic nephropathy. The therapeutic success is related to their action in reduction of plasma and tissue angiotensin II concentrations and potentiation of endogenous kinins. They are able to improve myocardium metabolic status, prevent cardiac hypertrophy, limit myocardial infarct size, and thus prevent heart failure. Since 1987 ACE inhibitors are introduced in the clinical practice in our clinic. We introduced the therapy with lisinopril (Lopril), in 70% of patients among 2855 patients that were admitted in Coronary Care Unit in 1997 and 1998. Lisinopril was introduced as soon as the patient was admitted, together with fibrinolitic, Heparin and Aspirin therapy. Since that time we noticed decrease in postinfarction heart failure in comparison to previous years. We recommend permanent therapy with a small doses of ACE inhibitors in patients with heart infarction.
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PMID:[Converting enzyme inhibitors in acute myocardial infarct and heart failure]. 1035 28

The renin-angiotensin system has two roles in clinical hypertension: its vasoconstrictor properties directly govern blood pressure, and its actions on arterial smooth muscle, connective tissue, and endothelial integrity affect cardiovascular prognosis. Additionally, the direct actions of angiotensin II on the function and structure of the heart and renal vasculature influence clinical events. Angiotensin-converting enzyme (ACE) inhibitors have produced functional and clinical outcome benefits in clinical trials of patients with congestive heart failure, systolic dysfunction after myocardial infarction, and diabetic nephropathy. Similar favorable trends have been noted in observational studies in hypertension. Because such enzymes as chymase can substitute for ACE, the ACE inhibitors may not completely block angiotensin II formation, although they enhance bradykinin accumulation and secondarily stimulate nitric oxide and vasodilatory prostaglandins. Angiotensin II receptor blockers (ARB) selectively block the angiotensin II type 1 (AT1) receptor that not only mediates the known effects of angiotensin II but, according to recent reports, might be responsible for sequestering angiotensin II molecules in renal and cardiac cells. Moreover, by increasing plasma concentrations of angiotensin II, the ARB stimulate the unblocked angiotensin II type 2 (AT2) receptors, which-if they exist in meaningful numbers in human hypertension-mediate additional vasodilatory and antiproliferative effects. The contrasting actions of these two classes of drugs might be clinically relevant. For example, they may have additive antihypertensive efficacy; they have differing effects on renal plasma flow; and in a small pilot study of patients with congestive heart failure, the ARB demonstrated an apparent advantage in survival. Ongoing clinical trials will try to determine whether the effects of ARB can equal or even exceed the beneficial effects of ACE inhibitors on cardiovascular prognosis.
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PMID:Interrupting the renin-angiotensin system: the role of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the treatment of hypertension. 1061 71

ACE inhibitors are a widely prescribed class of drug for the management of hypertension. Their therapeutic role in the treatment of heart failure, diabetic nephropathy and post myocardial infarction with left ventricular dysfunction is steadily increasing. Although ACE inhibitors have a similar mechanism of action--namely, inhibition of circulatory ACE, thereby decreasing the formation of angiotensin II--individual members differ in their physicochemical properties, enzyme-binding kinetics, pharmacokinetic profile, organ-specific affinity and selectivity, as well as in their bradykinin potentiating effect. These factors play an important part in influencing the pharmacological profile of an agent and its clinical efficacy, especially in the treatment of hypertension. It is therefore prudent to take into account the existing pharmacological and clinically relevant differences between the individual members of this drug class before making the decision to select a particular ACE inhibitor for the long-term management of arterial hypertension.
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PMID:Management of hypertension and its sequelae with ACE inhibitors: biochemical, pharmacological and clinical aspects. 1062 92

In 1989, we conducted a survey (UREMIDIAB) on the prevalence of diabetes among the population on Renal Replacement Therapy (RRT) in Mainland France (MF), the lowest of the developed countries (6.9%) with a North-South gradient (higher prevalence in the North). This highlighted a possible (genetical or nutritional) "new french paradox" in mainland France populations. In 1992 we conducted a similar study in the french (mainly non caucasian) overseas territories (OT) hosting 3.2% of the total french population, and observed a prevalence of diabetes in RRT of 22.9%. The frequency of diabetes mellitus as a cause of ESRD increasing worldwide, we conducted a second survey in year 1995, in MF and the OT. This study, UREMIDIAB 2, included all of the 244 french dialysis centers. A "Center file" allowed us to determine the prevalence and incidence of diabetes in the french RRT population, (response rate 73%). Then a "Patient medical file" (response rate 64.8% for MF and 91% for the OT) provided detailed informations: type of diabetes (type 1 or 2), etiology of nephropathy, status of diabetic complications, family's geographic origin of the patient. In MF the prevalence of diabetics in RRT doubled within 6 years: 13.04% vs 6.9%, the incidence reached 15.7%. In the OT the prevalence and the incidence reached 25.7% and 35.6%, respectively. Type 2 diabetes represented 87% and 93% of the RRT diabetics in MF and the OT, respectively. Diabetic nephropathy was considered as the cause of renal failure in 91.3% of type 1 and 57.5% of type 2 diabetics under dialysis. We found: 14.7% of myocardial infarction, 12.7% of cerebral strokes, 17.6% of amputations (extreme 37% in some OT centers) among this diabetic RRT population. A North-East (higher prevalence) South-West (lower) gradient was confirmed. We conclude that, while an unusual low prevalence (< or = 13%) of diabetics under dialysis persists in some parts of Mainland France, the total prevalence has been doubled within 6 years (1989/95) and that in Overseas Territories, hosting similar mixed blood populations than USA (afro-caribbeans, asians, indians, micronesians and metis), the high incidence of diabetes in RRT has reached the US levels during the same period.
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PMID:Huge progression of diabetes prevalence and incidence among dialysed patients in mainland France and overseas French territories. A second national survey six years apart. (UREMIDIAB 2 study). 1063 76

The influence of diabetes mellitus and complications on the long-term outcome of coronary artery bypass graft surgery (CABG) was investigated in 192 consecutive patients who underwent elective CABG between January 1992 and March 1996. Of these, 102 patients were diabetic and 90 were nondiabetic. Preoperative and postoperative left ventricular ejection fraction, number of grafts, use of arterial conduit, and frequency of perioperative infarction were all similar in the 2 groups. During a mean follow-up of 3.2 years, diabetics showed higher cardiac mortality than nondiabetics (15% vs 3%, p = 0.01). Cardiac event-free survival was also low in diabetics, and this difference increased throughout the period (91% vs 99% at 2 years, 74% vs 90% at 4 years in diabetics and nondiabetics, respectively, by Kaplan-Meier analysis, p = 0.008). Multivariate Cox regression analysis revealed postoperative low ejection fraction and diabetes mellitus as independent predictors of late cardiac death. Major causes of cardiac death in diabetics were sudden death, pump failure and acute myocardial infarction. Additionally, subgroup analysis in diabetics using the Cox regression model identified postoperative low ejection fraction, female gender and diabetic nephropathy as independent predictors of late cardiac death. Thus, patients with diabetes have a worse clinical outcome after CABG, especially when associated with low ejection fraction, female gender and diabetic nephropathy. Intensive management of heart failure, prevention of myocardial infarction and specific strategy for female patients are all essential to improve the long-term outcome of diabetics after CABG.
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PMID:[Influence of diabetes mellitus and complications on long-term outcome of coronary artery bypass surgery]. 1065 45

We retrospectively evaluated the factors that are prognostic in long-term continuous ambulatory peritoneal dialysis (CAPD). From 1986 to 1997, 91 CAPD patients (59 male, 32 female, mean age 48 years) entered the study. Their primary renal diseases were chronic glomerulonephritis (CGN, n = 80), diabetic nephropathy (DN, n = 10), and polycystic kidney disease (PKD, n = 1). The roles of primary renal disease, hypertension, left ventricular hypertrophy (LVH), left ventricular ejection fraction (LVEF), cardiac sympathetic activity, anemia, hypoalbuminemia, and plasma concentration of parathyroid hormone (PTH) on patient prognosis were analyzed. Among the 91 CAPD patients, 26 died during the observation period. Of these deaths, 17 resulted from cardiovascular diseases including cerebrovascular events (n = 7), myocardial infarction (n = 2), sudden death (n = 7), and aortic aneurysmal rupture (n = 1). Nine patients died of non cardiovascular events. Sclerosing encapsulating peritonitis and others, mainly cachexia, accounted for 2 and 7 of these deaths, respectively. The 5-year survival rate was 74%; the 10-year rate was 49%. The cumulative 5- and 10-year success rates of CAPD were 69% and 39%, respectively. DN, hypertension, severe LVH (more than 200 g/m2), and hypoalbuminemia were contributors to poor prognosis. Among these, DN and severe LVH were the two main predictors by Cox proportional hazards model. We conclude that CAPD patients with DN or severe LVH, or both, have a greater chance of drop-out from cardiovascular events.
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PMID:Predictors of survival in continuous ambulatory peritoneal dialysis patients: the importance of left ventricular hypertrophy and diabetic nephropathy. 1068 78

Early detection and adequate treatment of complications of diabetes mellitus (DM) are important for many patients in maintaining independence and ability to work. Diabetic retinopathy cannot be prevented. Limitation of damage is possible by aiming for normoglycaemia and normotension. While exudative as well as proliferative retinopathy can occur without any visual symptom, regular ophthalmological examination is necessary for timely laser coagulation. Fundus photography for screening is applicable under certain conditions; fluorescence angiography can be useful in patients with understood deterioration of visual acuity or diabetic maculopathy. In many patients foot disease can be prevented by simple measures: examining the foot at least once a year, recognition of the foot with a high level of risk, education of patient and family, adapted shoes and preventive foot care. Treatment of a foot ulcus consists of relief of mechanical pressure, repair of disturbed skin circulation, treatment of infection and oedema, optimal metabolic control, frequent local wound care and education. Patients with a diabetic foot have to be thoroughly followed up for the rest of their lives. For patients with diabetic nephropathy cardiovascular complications are the main causes of morbidity and mortality. Of all patient with DM older than 10 years urine has to be examined for loss of albumin at least once a year. Treatment of nephropathy consists of non-smoking, sufficient physical exercise, reduction of overweight, well-composed nutrition and particularly treatment of hypertension. Diagnosing cardiovascular diseases in patients with DM is in principle the same as for other patients. Treatment of hypercholesterolaemia has to be based on an absolute risk of 20% for cardiovascular disease in the following 10 years. The limit for treatment will be reached earlier in the presence of microalbuminuria, persistent high HbA1c > 8.5%, triglyceride concentration > 2.0 mmol/l, or a positive family history with myocardial infarction < 60 years. In proven cardiovascular disease one needs to strive for optimalization of the glucose metabolism, non-smoking and if necessary drug therapy.
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PMID:[CBO guidelines on diagnosis, treatment, and prevention of complication in diabetes mellitus: retinopathy, foot ulcers, nephropathy and cardiovascular diseases. Dutch Institute for Quality Assurance]. 1071 45

Hyperglycemia may lead to atherosclerosis by different pathogenic mechanisms. Nonenzymatic glycation and oxidation of LDL may increase its atherogenicity. Glycation may modify some arterial wall structural proteins. Increased blood glucose leads to hypertriglyceridemia which results in decrease of HDL-cholesterol level and in increase of atherogenic dense LDL particles. Hyperglycemia also adversely affects processes of platelet aggregation, hemocoagulation and fibrinolysis. It accelerates the development of diabetic nephropathy--a condition with a high prevalence of macrovascular diseases. Prospective epidemiologic studies have shown that diabetic patients in worse metabolic control had an increased cardiovascular morbidity and mortality. Therapeutic randomized studies in type 1 (DCCT) and type 2 (UKPDS) diabetic patients have shown that better diabetes control had a preventive effect against development of microvascular complications. The incidence of macrovascular complications both in type 1 diabetic patients on intensive insulin or sulfonylurea treatment has been decreased on the level of borderline statistical significance. Metformin lead to a significant decrease in myocardial infarction incidence in the subgroup of obese type 2 diabetic patients. In conclusion, maximal possible metabolic control of diabetes prevents the development of microvascular complication, but more impressive decrease in macrovascular disease incidence probably requires to affect another important risk factors for atherosclerosis, such as dyslipidemia and hypertension.
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PMID:[Hyperglycemia and atherosclerosis. Causal relation or association?]. 1095 84


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