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Query: UMLS:C0011881 (diabetic nephropathy)
10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Where shall we place angiotensin receptor blockers in the scheme of the prevention of diabetic nephropathy? Only the results of a large, randomized double-blind trial with a comparable and appropriate alternative would prove therapeutic efficacy. The results of several trials with angiotensin-converting enzyme (ACE) inhibitors have proven them to be the standard of care for diabetics and their kidneys. As reviewed in this article, the results of three large such clinical trials have recently been completed with angiotensin receptor blockers in patients with type 2 diabetes mellitus. Initial results appear favorable. However, whether angiotensin blockers have more to offer than ACE inhibitors is still speculative. The renin-angiotensin system plays an important role in the pathogenesis of diabetic nephropathy. Since alternative pathways to ACE have been uncovered in the formation of angiotensin II, inhibition at the final end point would provide favored blockade. Because angiotensin receptor blockers do provide this specific blockade, they offer far more promise than ACE inhibitors.
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PMID:Angiotensin receptor blockers in diabetic nephropathy. 1264 9

The renin-angiotensin-aldosterone system (RAAS) exerts a principal influence in maintaining vascular tone, optimal salt and water homeostasis, and forward cardiac output in human beings. Overactivity of the RAAS can lead to pathologic consequences in states of diabetic nephropathy, hypertension, renal artery stenosis, left ventricular hypertrophy, coronary atherosclerosis, myocardial infarction, and congestive heart failure. In addition to fluid and hemodynamic effects, the RAAS may have a critical role in the activation of the sympathetic nervous system, the progression of atherosclerosis, the dysregulation of endothelial function, and the inhibition of the fibrinolytic system. Accumulated basic and clinical evidence supports the use of inhibitors of the RAAS, including aldosterone antagonists, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, in treating hypertension, improving diabetic nephropathy, preventing or ameliorating congestive heart failure, and optimizing the prognosis after myocardial infarction.
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PMID:Renin-angiotensin-aldosterone system: fundamental aspects and clinical implications in renal and cardiovascular disorders. 1267 84

Guidelines for medical treatment are becoming increasingly popular and many guidelines have been produced by various societies in diabetes, hypertension, and renal disease as well as general medicine. By their nature, they are outdated considering the rapid and efficient publication of many papers related to the treatment of hypertension in diabetes. Increased blood glucose causes vascular damage and abnormal vascular structure all over the body, an abnormal structure that is especially vulnerable to high blood pressure, even within the so-called normal range. There is now more and more evidence, especially in diabetics, that blood pressure should be as low as possible. In this context, it is important to stress that the so-called J-shaped relationship between blood pressure and mortality may not be so relevant. Major epidemiological studies came from the Framingham and the Multiple Risk Factor Intervention Trial (MRFIT) Diabetic Cohort. The MRFIT Cohort showed that cardiovascular mortality was increased by a factor of 2-4 in diabetic patients, and there was a clear association between systolic blood pressure and complications without any threshold value. It could be suggested that since diabetes is an important cardiovascular risk factor, a lower value (130/85 mmHg) than for non-diabetics (140/90 mmHg) should be proposed. The tight blood pressure control arm of the United Kingdom Prospective Diabetes Study was <150/85 mmHg (achieved 144/82 mmHg) and the aim in the less tight control arm was <180/105 mmHg (achieved 154/87 mmHg). In the tight control group, 29% needed three or more antihypertensive drugs. In the Hypertension Optimal Treatment study, the frequency of major cardiovascular disease events in the group with target <80 mmHg (achieved 144/81 mmHg) was 11.9/1000 patients/year, which was significantly lower than the event rate (24.4/1000 patients/year) in the group with target <90 mmHg (achieved 148/85 mmHg). A reduction in the frequency of diabetic nephropathy by angiotensin-converting enzyme (ACE) inhibitor treatment in normotensive lean microalbuminuric type 2 diabetic patients has been shown. However, it is impossible from the present data to draw any conclusions with respect to effect on the main composite endpoint of ACE inhibition in microalbuminuric type 2 diabetic patients without previous cardiovascular events or without hypertension. Recent published studies have also demonstrated beneficial effects with angiotensin receptor blockers (ARBs) in hypertensive patients with type 2 diabetes and nephropathy. Diuretics form a very important basis for antihypertensive treatment, also often in combination with agents that inhibit the renin-angiotensin system. Several studies show that treatment with the diuretic indapamide reduces the level of microalbuminuria in patients with type 2 diabetes. Diuretics were used as an adjunctive to reduce blood pressure in all studies; it is therefore understandable that many guidelines suggest that diuretics form part of the treatment of hypertension in diabetics. Many studies of an epidemiological nature and follow-up studies in diabetic patients show that blood pressure control is of vital concern in the prevention of diabetic complications, and indeed the usual criteria for good blood pressure control may not be stringent enough in diabetic patients. Many classes of antihypertensives may be used, but it appears that diuretics, such as indapamide sustained release (SR), constitute an important proposal in all treatment strategies.
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PMID:New treatment guidelines for a patient with diabetes and hypertension. 1276 64

As the epidemic of diabetes spreads so does the number of patients at risk for developing diabetic nephropathy, which occurs in 20% to 40% of all diabetic patients. Indeed, diabetes is the most common cause of end-stage renal disease (ESRD) in the United States, accounting for > 40% of patients starting renal replacement therapy each year. Unfortunately, the outcome for diabetic patients with ESRD is worse than that for nondiabetic patients because of comorbid conditions in the diabetic population. However, with early and intensive blood glucose and blood pressure control--including the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers--the development and progression of diabetic kidney disease can be slowed.
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PMID:Diabetic nephropathy. 1280 Apr 76

Blockade of the effects of angiotensin II (Ang II) by using an angiotensin-converting enzyme (ACE) inhibitor has been proven to be of value in Type 1 diabetic nephropathy and in non-diabetic renal disease. Evidence in favour of Ang II blockade in Type 2 diabetic patients with renal damage is still lacking for ACE inhibitors (ACE-Is), while recent data indicate that angiotensin receptor blockers (ARBs) could be the drugs of choice in this situation. On the other hand, renal damage from the onset of disease is accompanied by a very significant increment in global cardiovascular risk. This fact, as well as that of simultaneous renal and cardiovascular protection, have to be considered for drug selection. In this sense, ACE-Is have been shown to be the drugs of choice when secondary cardiovascular prevention is required, while the evidence in primary prevention in hypertensive patients has been shown with losartan in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. All these facts led to the conclusion that both ACE-Is and ARBs can be considered when both renal and cardiovascular protection are aimed for in Type 2 diabetic patients.
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PMID:ACE inhibition or angiotensin receptor blockade: which should we use in diabetic patients? 1280 88

Combination therapy with angiotensin receptor antagonist(ARB) plus angiotensin converting enzyme inhibitor(ACE-I) (ARB/ACE-I) was efficacious in reducing proteinuria in patients with progressive renal disease. However, this therapy may be associated with the worsening of anemia and hyperkalemia. The present study addressed whether or not triple therapy with low-dose ARB, low-dose diuretic (D) and calcium channel blocker(CCB) (ARB/D/CCB) is as effective as therapy with low-dose ARB/ACE-I in retarding the progression of overt diabetic nephropathy. In the triple therapy, the patients were initially subjected to monotherapy with CCB for 24 weeks. Low-dose ARB and low-dose D were added to the treatment for an additional 24-week period. In parallel, patients undergoing double therapy were initially treated with low-dose ACE-I alone for 24 weeks, and then low-dose ARB was added for an additional 24-week period. The results were as follows: 1) In the triple therapy, blood pressure was reduced by 9 mmHg in systole and 5 mmHg in diastole (not significant) compared to monotherapy with CCB. There was a significant decline in proteinuria (3.3 +/- 1.2 g/day in the CCB-treated period vs. 2.1 +/- 1.0 g/day in the ARB/D/CCB-treated period, n = 12, p = 0.0143). Furthermore, a significant improvement in the slope of reciprocal serum creatinine concentration(1/Cr) was found in response to triple therapy(1/Cr: -0.0118 +/- 0.0009 in the CCB-treated vs. -0.0035 +/- 0.0028(I/mg/dl/month) in the ARB/D/CCB-treated period, n = 12, p < 0.001). There was neither a worsening of anemia nor an increase in the serum potassium(K) concentration. 2) In the double therapy, blood pressure was reduced by 12 mmHg in systole(p = 0.0079, n = 11) and 6 mmHg in diastole(n = 11, p = 0.0037) compared to the monotherapy with ACE-I. A significant improvement in the slope of 1/Cr was found in the double therapy(1/Cr: -0.0095 +/- 0.0052 in the ACE-I treated period vs. -0.0029 +/- 0.0028(I/mg/dl/month) in the ARB/ACE-I, n = 11, p < 0.001). In addition, there was a substantial reduction in hematocrit and increase in serum K concentration. The present result suggests that triple therapy consisting of ARB/D/CCB is as efficacious as double therapy with ARB/ACE-I in protecting the kidney from the progression in patients with diabetic overt nephropathy. The former may be expected to have less adverse effects.
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PMID:[Renoprotective effect of triple therapy with low-dose angiotensin receptor blocker, low-dose diuretic and Ca-antagonist in hypertensive type 2 diabetic patients with overt nephropathy]. 1280 73

The renin-angiotensin-aldosterone system (RAAS) plays an integral role in maintaining vascular tone, optimal salt and water homeostasis, and cardiac function in humans. However, it has been recognized in recent years that pathologic consequences may also result from overactivity of the RAAS. Clinical disease states such as renal artery stenosis, hypertension, diabetic and nondiabetic nephropathies, left ventricular hypertrophy, coronary atherosclerosis, myocardial infarction, and congestive heart failure (CHF) are examples. Part of the adverse cardiorenal effects of the RAAS may be related to the prominent role that this system plays in the activation of the sympathetic nervous system, the dysregulation of endothelial function and progression of atherosclerosis, as well as inhibition of the fibrinolytic system. Also, direct profibrotic actions of angiotensin II and aldosterone in the kidney and heart promote end organ injury. Current basic science and clinical research supports the use of inhibitors of the RAAS, including angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists in treating hypertension, improving diabetic nephropathy and other forms of chronic kidney disease, preventing or ameliorating CHF, and optimizing prognosis after myocardial infarction.
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PMID:The renin-angiotensin-aldosterone system: cardiorenal effects and implications for renal and cardiovascular disease states. 1286 Nov 21

The relationship between the renin-angiotensin system (RAS) and the progression of diabetic renal disease has been a major focus of investigation over the past 20 years. More recently, experimental and clinical studies have also suggested that the RAS may have a pathogenetic role at other sites of micro- and macrovascular injury in diabetes. Complementing major advances into the understanding of the local, as distinct from the systemic RAS, a number of large clinical trials have examined whether blockade of the RAS might provide protection from the long-term complications of diabetes, beyond that due to blood pressure reduction alone. While some controversy remains, these studies have, in general, suggested that angiotensin converting enzyme (ACE) inhibition and more recently, angiotensin receptor blockade reduce the development and progression of diabetic nephropathy, cardiovascular disease and possibly retinopathy. This review will focus on recent developments in our understanding of the tissue-based RAS and its role in end-organ injury in diabetes, the results of recent clinical trials and newer strategies for the pharmacological manipulation of the RAS.
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PMID:The renin-angiotensin system and the long-term complications of diabetes: pathophysiological and therapeutic considerations. 1287 87

Patients with diabetes mellitus are often associated with hypertension. Hypertension increases the incidence of cardiovascular disease and accelerates the progression of diabetic nephropathy. Japanese Society of Hypertension made own guidelines for the management of hypertension(JSH2000) in 2000. Diabetics are stratified into the high risk group irrespective of their blood pressure levels. Target blood pressure is less than 130/85 mmHg. Hypotensive agents will be initiated at more than 140/90 mmHg along with glycemic control and lifestyle modification. When their blood pressure is within the high normal(130-139/85-89 mmHg), lifestyle modification as well as glycemic control will be initiated. If their blood pressure is not lowered to less than 130/85 mmHg during the next 3-6 months, hypotensive agents will be started. ACEIs, Ca-antagonists and alpha-blockers will be the first line hypotensive agents, since these hypotensive agents improve organ damages and insulin sensitivity and do not worsen lipid metabolisms. Recent guideline made by Japan Diabetes Society in 2003 lowered the target blood pressure furthermore to less than 130/80 mmHg and added angiotensin receptor blockers as one of the firstline hypotensive agents.
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PMID:[Guidelines for the treatment of hypertension in diabetics]. 1287 84

Increased oxidative stress has an important role in the pathogenesis of diabetic nephropathy. The aim of this study was to evaluate the effects of renin-anigiotensin system blockage, either by angiotensin-converting enzyme inhibition or angiotensin receptor blockage, on oxidative stress and nitric oxide release in diabetic rat kidneys. After induction of diabetes, six rats were given captopril, six rats were given losartan, and six rats served as diabetic controls. Six healthy rats were also included. At the end of an 8-week period nitric oxide release, lipid peroxidation and protein oxidation were measured in kidney cortices, and urinary albumin excretion (UAE) was determined in 24-h urine samples. Losartan- and captopril-treated diabetic rats had lower levels of UAE than diabetic controls. Diabetic rats had higher levels of lipid peroxidation and protein oxidation compared to healthy rats. NO release was significantly lower in diabetic groups than healthy controls. UAE levels showed a positive correlation with lipid peroxidation and a negative correlation with NO release. Inhibition of lipid peroxidation could be one of the protective mechanisms of renin-angiotensin axis inhibition in diabetic kidney tissues.
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PMID:Effects of captopril and losartan on lipid peroxidation, protein oxidation and nitric oxide release in diabetic rat kidney. 1290 31

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