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)

In the present quantitative overview of outcome trials, we investigated the efficacy of amlodipine or angiotensin receptor blockers in the prevention of stroke and myocardial infarction in patients with hypertension, coronary artery disease, or diabetic nephropathy. The analysis included 12 trials of 94 338 patients. The analysis of trials involving an amlodipine group showed that amlodipine provided more protection against stroke and myocardial infarction than other antihypertensive drugs, including angiotensin receptor blockers (-19%, P<0.0001 and -7%, P=0.03) and placebo (-37%, P=0.06 and -29%, P=0.04). The analysis of trials involving an angiotensin receptor blocker group showed contrasting results between trials versus amlodipine and trials versus other antihypertensive drugs for stroke (+19% versus -25%; P<0.0001) and myocardial infarction (+21% versus +1%; P=0.03). The results of 3 trials comparing an angiotensin receptor blocker with placebo were neutral (P> or =0.14). The within-trial between-group difference in achieved systolic pressure ranged from -1.1 to +4.7 mm Hg for trials involving an amlodipine group and from -2.8 to +4.0 mm Hg for trials involving an angiotensin receptor blocker group. The metaregression analysis correlating odds ratios with blood pressure differences showed a negative relationship (regression coefficients: -3% to -8%), which reached statistical significance (regression coefficient: -6%; P=0.01) for stroke in trials involving an amlodipine group. In conclusion, blood pressure differences largely accounted for cardiovascular outcome.
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PMID:Prevention of stroke and myocardial infarction by amlodipine and Angiotensin receptor blockers: a quantitative overview. 1772 73

Beneficial effects of angiotensin converting enzyme inhibitors (ACEI) and angiotensin type 1 receptor (AT1) blockers in patients with cardiovascular and renal diseases have been clearly demonstrated in numerous large outcomes studies. In patients with heart failure (HF), ACEI have been shown to reduce overall mortality, mortality from cardiovascular causes, to increase life expectancy, as well as to preserve the renal function (CONSENSUS, SAVE, TRACE, AIRE, AIREX, CATS trials). In addition, in the PROGRESS study ACEI substantially decreased the risk of stroke and transient ischemic attacks in patients with cerebrovascular disorders. The HOPE and EUROPA studies confirmed that long term therapy with ACEI provides significant survival benefit in patients with broad range of atherosclerotic cardiovascular diseases. After these large and well designed clinical studies, ACEI have become standard therapy for routine secondary prevention in all patients with cardiovascular diseases, unless contraindicated. AT1 receptor blockers have been recently added to the cardiovascular therapeutic armamentarium. They are believed to provide additional protection by inhibition of locally synthesized angiotensin II on the level of AT1 receptor. The ELITE II, ValHeFT and CHARM studies have shown that AT1 receptor blockers are equally effective as ACEI in reduction of mortality and morbidity in patients with HF. Importantly, they may be used together with ACEI, or as alternative treatment in ACEI intolerant patients. Renal protection is another important effect of both ACEI and AT1 blockers that has been confirmed in several large clinical trials. The North American Microalbuminemia Study group and EUCLID group demonstrated significant reduction in progression of diabetic nephropathy in patients with insulin dependent diabetes mellitus (IDDM) treated with ACEI. AT1 receptor blockers are mainly studied in the non-insulin dependent diabetes mellitus (NIDDM) nephropathy. Four recent clinical trials (IRMA-2, DETAIL, RENAAL and IDNT) examined the effect of AT1 receptor blockers in patients with NIDDM nephropathy. These studies confirmed the beneficial effect of AT1 receptor blockers in patients with NIDDM nephropathy that was extended beyond the blood pressure reduction. Ongoing studies (ONTARGET, TRANSCEND and PROTECTION) should provide us with additional insights about cardiovascular, renal and other end-organ protective effects of these therapeutics.
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PMID:Role of renin angiotensin system inhibitors in cardiovascular and renal protection: a lesson from clinical trials. 1750 19

Activation of inflammatory processes may contribute to the development of type 2 diabetes mellitus. In addition, inflammation appears to be a major mechanism responsible for vascular damage leading to the clinically well-recognized complications of diabetes. Inflammatory cytokine and chemokine mediators released from visceral fat contribute to atherosclerotic plaque formation and increased risk for myocardial infarction and stroke. Activation of growth factors and adhesion molecules may promote the movement of inflammatory cells into the renal microvasculature, predisposing to the development of diabetic nephropathy. Emerging evidence also indicates that markers of inflammation are associated with the more severe forms of diabetic retinopathy. Future approaches to the treatment of diabetic complications may involve regulation of inflammatory processes, specifically targeting factors that contribute to vascular damage.
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PMID:Inflammatory mechanisms of diabetic complications. 1754 42

Accelerated cardiovascular disease is a frequent complication of renal disease. Chronic kidney disease promotes hypertension and dyslipidemia, which in turn can contribute to the progression of renal failure. Furthermore, diabetic nephropathy is the leading cause of renal failure in developed countries. Together, hypertension, dyslipidemia, and diabetes are major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease, which likely contributes through enhanced production of reactive oxygen species to the accelerated atherosclerosis observed in chronic kidney disease. Promoters of calcification are increased and inhibitors of calcification are reduced, which favors metastatic vascular calcification, an important participant in vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Consequently, subjects with chronic renal failure are exposed to increased morbidity and mortality as a result of cardiovascular events. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with chronic kidney disease.
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PMID:Chronic kidney disease: effects on the cardiovascular system. 1760 56

Hypertension, a major cardiovascular disease risk factor, is increasing in India. Though several studies have studied the prevalence and causes of hypertension in India, only few have examined the control of blood pressure (BP) among people with hypertension. The I-Target survey was carried out to assess the extent of BP control among Indian patients with hypertension receiving antihypertension medications. A total of 270 physicians from four zones of India included 3402 patients with hypertension who were undergoing treatment. They collected information on BP levels, current medication and presence of other risk factors, and determined the average systolic and diastolic BP in hypertensive patients. Of the study population, 1435 patients (42.2%) had diabetes and 787 (23.1%) had coronary artery disease (CAD). Overall, 70.5% patients did not reach target systolic BP (SBP) goal and 36.9% patients did not reach diastolic BP (DBP) goal. Only 27.3% patients had both SBP and DBP under control. Among patients with diabetes, 81.1% had uncontrolled SBP and 76.2% had uncontrolled DBP. In patients with CAD, 71.8% of SBP and 38.5% of DBP readings were outside the recommended target BP levels. Regardless of comorbidities-hypercholesterolaemia, myocardial infarct, metabolic syndrome, stroke, diabetic nephropathy or obesity--the average SBP and DBP were higher than target BP levels. Among patients with hypertension, control of BP to recommended targets was very poor, only to the extent of 27.3%. The average BP of hypertensive patients with comorbidities like diabetes and CAD was also higher than the BP goals recommended by international and local guidelines. Thus, there is an urgent need to increase awareness among patients with hypertension and to ensure that BP goals are achieved.
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PMID:Blood pressure control among Indians with hypertension: the I-Target survey. 1817 98

The members of the NOX/DUOX family of NADPH oxidases mediate such physiologic functions as host defense, cell signaling, and thyroid hormone biosynthesis through the generation of reactive oxygen species (ROS), including superoxide anion and hydrogen peroxide. Moreover, ROS are involved in a broad range of fundamental biochemical and cellular processes, and data accumulated in recent years indicate that the NOX enzymes comprise one of the most important biological sources of ROS. Given the high biochemical reactivity of ROS, it is not surprising that they have been implicated in a wide variety of pathologies and diseases. Prominent among the settings that feature ROS-mediated tissue injury are disorders associated with inflammation, aging, and progressive degenerative changes in cells and organ systems, and it appears that essentially no organ system is exempt. Among the disorders currently believed to be mediated at least in part by NOX-derived ROS are hypertension, aortic aneurysm, myocardial infarction (and other ischemia-reperfusion disorders), pulmonary fibrosis and hypertension, amyotropic lateral sclerosis, Alzheimer's disease, Parkinson's disease, ischemic stroke, diabetic nephropathy, and renal cell carcinoma. Several small-molecule and peptide inhibitors of the NOX enzymes have been useful in experimental studies, but issues of specificity, potency, and toxicity militate against any of the existing published compounds as candidates for drug development. Given the broad array of disease targets documented in recent work, the time is here for vigorous efforts to develop clinically useful inhibitors of the NOX enzymes. As most (though not all) NOX-related diseases appear to be mediated by a single member of the NOX family, agents with isoform specificity will be preferred, although broadly active NOX inhibitors may prove to be useful in some settings.
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PMID:NOX enzymes as novel targets for drug development. 1850 46

The prevalence of cardiovascular risk factors in renal transplant candidates is high. A better understanding of the relation between these risk factors and cardiovascular morbidity and mortality is mandatory to improve transplantation outcome. In this retrospective cohort study 2187 adult patients who received a first kidney transplant between 1984 and 1997 were included. We analyzed the incidence of post-transplant cardiovascular events and tried to identify independent pretransplant risk factors for post-transplant cardiovascular events and all-cause mortality. The cumulative incidence of post-transplant cardiovascular events was 40%. The incidence was highest in the first 3 months after transplantation. Independent pretransplant risk factors for a post-transplant cardiovascular event were diabetic nephropathy [Hazard ratio (HR) 3.02; 95% CI 2.85-3.98], claudication [HR 2.17 (1.42-3.31)], cardiac event [HR 1.76 (1.32-2.33)], cerebrovascular accident HR 1.53 (1.03-2.28), time-on-dialysis [HR 1.06 (1.02-1.11)], recipient age [HR 1.04 (1.04-1.05)], and body mass index [HR 1.03 (1.00-1.05)]. Diabetic nephropathy and cardiovascular disease were also important predictors for all-cause mortality. Diabetic nephropathy and cardiovascular disease were the most important predictors for cardiovascular events and all-cause mortality after renal transplantation. Early treatment of cardiovascular risk factors and pretransplant cardiovascular evaluation might improve transplantation outcome.
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PMID:Associations between pre-kidney-transplant risk factors and post-transplant cardiovascular events and death. 1856 85

The Angiotensin II receptor blockers (ARBs) have been efficacious and safe drugs for the treatment of hypertension, heart failure, diabetic nephropathy and stroke from several short and long term clinical trials. The ARBs exert their effects through selective blockade of the angiotensin II (Ang-II) subtype 1 (AT1) receptor and quite possibly through stimulation by Ang-II of the unoccupied subtype 2 (AT2) receptor. The ARBs are equipotent to other antihypertensive drugs with respect to their effect on blood pressure, heart failure or diabetic nephropathy. They appear to be superior to the other drugs with respect to their stroke protective effect. They exert their stroke protective effect by a dual action, selectively blocking the action of Ang-II on the AT1 receptors, while allowing Ang-II to stimulate the unoccupied AT2 receptors. This dual action is unique to ARBs and results in vasodilation and increase in blood flow to the ischemic zone of the brain leading to improvement and prevention of its extension. All these actions of the ARBs will be discussed in this comprehensive review.
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PMID:Clinical experience with the use of angiotensin receptor blockers in patients with cardiovascular, cerebrovascular and renal diseases. 1866 66

Angiotensin receptor blockers (ARBs), through their physiological blockade of the renin-angiotensin system, reduce morbidity and mortality associated with hypertension, heart failure, myocardial infarction, stroke, diabetic nephropathy, and chronic kidney disease. Among many attributes, excellent tolerability, and their ability to control hypertension for 24 hours with a positive effect on renal function position them as a useful choice for hypertension and related conditions. Because of the widespread actions of the renin-angiotensin system on critical tissues, treatment with ARBs may be beneficial in special populations. Ongoing and future studies will be needed to conclusively determine if ARBs also improve outcomes in patients with heart failure and preserved systolic function, atrial fibrillation, cognitive dysfunction, and kidney transplant recipients. Preliminary clinical data also suggest that combining ARBs and angiotensin-converting enzyme inhibitors may provide a more optimal blockade of the renin-angiotensin system and, therefore, may offer greater cardio- and nephroprotection. Future data will help delineate which ARBs and angiotensin-converting enzyme inhibitors are best combined and which patient populations might benefit from the dual blockade of the renin-angiotensin system.
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PMID:Angiotensin receptor blockers: current status and future prospects. 1869 75

Among hypertensive cardiovascular complications only end-stage renal failure (ESRD) is progressively increasing, while the increases in the incidence of stroke and coronary heart disease have been suppressed. On the other hand, it is well established that CKD, especially due to diabetic nephropathy and IgA nephropathy, can be arrested into complete remission if treated in the early stages. Therefore, early detection program is highly and urgently required. To achieve this goal, we must consider what we can do now in nation-wide scale including patients, doctors and governments. There are remarkable regional differences in both the incidence of ESRD and the increasing rate within Japan. Japanese Society of Dialysis Therapy has the unique system to register the patients who reach ESRD, resulting in chronic dialysis therapy. Therefore, if we can build the patient identification system compatible to the above, then we immediately know who has reached ESRD. In this way, we can analyze the backgrounds of the ESRD patients to find out the risk factors of CKD in addition to the regional differences. I anticipate that the incidence of ESRD will be reduced in near future in Japan as seen in diabetic nephropathy in Denmark and USA. We must act now to accomplish this important issue: integrated care of CKD.
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PMID:[Integrated care and expected outcomes over the progression of CKD (chronic kidney disease)]. 1878 14


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