UMLS:C0011881 - FACTA Search

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

Angiotensin-converting enzyme (ACE) has a critical role in cardiovascular function by cleaving the carboxy terminal His-Leu dipeptide from angiotensin I to produce a potent vasopressor octapeptide, angiotensin II. Inhibitors of ACE are a first line of therapy for hypertension, heart failure, myocardial infarction and diabetic nephropathy. Notably, these inhibitors were developed without knowledge of the structure of human ACE, but were instead designed on the basis of an assumed mechanistic homology with carboxypeptidase A. Here we present the X-ray structure of human testicular ACE and its complex with one of the most widely used inhibitors, lisinopril (N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline; also known as Prinivil or Zestril), at 2.0 A resolution. Analysis of the three-dimensional structure of ACE shows that it bears little similarity to that of carboxypeptidase A, but instead resembles neurolysin and Pyrococcus furiosus carboxypeptidase--zinc metallopeptidases with no detectable sequence similarity to ACE. The structure provides an opportunity to design domain-selective ACE inhibitors that may exhibit new pharmacological profiles.
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PMID:Crystal structure of the human angiotensin-converting enzyme-lisinopril complex. 1254 Aug 54

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

The main peripheral sources of 5-hydroxytryptamine (5-HT) are as a neurotransmitter and local hormone in the gastrointestinal tract, and stored in circulating platelets and pulmonary neuroepithelial bodies. 5-HT has been shown to have many possible physiological and pathophysiological roles on the cardiovascular and renal systems. Thus, 5-HT may contribute to valvular heart disease, coronary artery disease, pulmonary hypertension, pulmonary embolism, pre-eclampsia, peripheral vascular disease and diabetic nephropathy. Consequently, modulators of the 5-HT system have diverse clinical potential. For instance, selective 5-HT subtype 3 receptor (5-HT(3)) antagonists may have potential in the treatment of the pain associated with myocardial infarction. MCI-9042 (sarpogrelate) or other 5-HT(2A) antagonists may have clinical potential for the treatment of vasospastic angina, ischaemic heart disease, reperfusion injury and hindlimb ischaemia. Several modulators of 5-HT (5-HT transporter inhibitors, 5-HT(1B) and (2B) antagonists) may have potential alone or in combination in the treatment of pulmonary hypertension. In hypertension, agonists at the 5-HT(7) and antagonists at the 5-HT(2B) may reduce blood pressure, and in diabetes, sarpogrelate may protect against nephropathy.
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PMID:The role of 5-HT on the cardiovascular and renal systems and the clinical potential of 5-HT modulation. 1272 Apr 92

In this article, 2 leading physicians debate the strength of outcome data on the efficacy of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs) for reducing the incidence of cardiovascular, cerebrovascular, and renovascular events. Dr. Stephen G. Ball notes that the efficacy of ACE inhibitors for reducing the risk for myocardial infarction independent of their effects on blood pressure is controversial. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril treatment in high-risk patients was associated with a 20% reduction in the risk for myocardial infarction; mean reduction in blood pressure was 3 mm Hg for systolic blood pressure and 1 mm Hg for diastolic blood pressure. The HOPE investigators propose that the 20% reduction was much greater than would be expected based on the observed blood pressure reduction. However, a meta-regression analysis of blood pressure reduction in >20 antihypertensive therapy outcome trials found that the reduction in myocardial infarction risk with ramipril observed in HOPE was consistent with the modest blood pressure reduction seen with that agent. Nevertheless, there are convincing data for prevention of myocardial infarction with ACE inhibitors in patients with heart failure, including those with heart failure after myocardial infarction, as well as supportive evidence from studies in patients with diabetes mellitus and concomitant hypertension. On the other hand, Dr. William B. White takes the position that ARBs are well-tolerated antihypertensive agents that specifically antagonize the angiotensin II type 1 (AT(1)) receptor and provide a more complete block of the pathologic effects of angiotensin II-which are mediated via the AT(1) receptor-than ACE inhibitors. The Evaluation of Losartan in the Elderly (ELITE) II study and the Valsartan Heart Failure Trial (ValHeFT) suggest that ARBs reduce the risk for mortality in patients with congestive heart failure. The Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension trial also demonstrated beneficial effects of ARBs in the prevention of stroke events. The Irbesartan in Patients with Diabetes and Microalbuminuria (IRMA) study, the Irbesartan Diabetic Nephropathy Trial (IDNT), and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated significant reductions in the rate of progression of renal disease in patients receiving ARBs, independent of effects on blood pressure. These data support the use of ARBs, in addition to the standard of care, in hypertensive patients with heart failure who are intolerant of ACE inhibitors, and also provide compelling evidence for their use in patients with hypertension and type 2 diabetes.
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PMID:Debate: angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers--a gap in evidence-based medicine. 1451 6

When planning treatment for patients with hypertension, current guidelines emphasise the importance of risk stratification, based on blood pressure, the presence of end-organ damage and other cardiovascular risk factors. Because the beneficial effect of antihypertensive therapy seems to be linked to the degree of blood pressure reduction, guidelines recommend reducing blood pressure below 140/90mm Hg, with a lower target in patients who are young or who have diabetes mellitus (with or without nephropathy) or non-diabetic nephropathy. Blood pressure reduction can be achieved with several classes of drugs, including diuretics, beta-blockers, ACE inhibitors, angiotensin II antagonists and calcium channel antagonists. Calcium channel antagonists have been shown to reduce the risk of stroke and major cardiovascular events. However, it is still controversial whether different treatment regimens based on different drug classes can offer advantages beyond similar degrees of blood pressure control in preventing cardiovascular morbidity and mortality. The International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) was a controlled clinical trial aimed at comparing the efficacy of a long-acting calcium channel antagonist, nifedipine gastrointestinal-transport-system (GITS), versus co-amilozide, a combination of the diuretics hydrochlorothiazide (HCTZ) and amiloride, on morbidity and mortality in high-risk hypertensive patients. Nifedipine GITS and HCTZ/amiloride were equally effective at reducing blood pressure and the risk of primary outcomes (a composite of death from any cardiovascular or cerebrovascular cause, non-fatal stroke, myocardial infarction and heart failure). Results from other studies indicate that there may be greater benefits for stroke and smaller benefits for coronary artery disease with calcium channel antagonist-based regimens than with diuretic or beta-blocker-based regimens. However, there is at present insufficient evidence to recommend a specific drug choice based on patient risk profile. Thus, the choice of antihypertensive drug(s) should be according to efficacy and tolerability. In addition to the reductions in cardiovascular risk, two substudies of INSIGHT showed that nifedipine GITS was able to prevent the progression of intima media thickness in the common carotid artery and slow the progression of coronary calcification. The clinical significance of this effect in the prevention of cardiovascular events still remains to be established.
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PMID:Current treatment of patients with hypertension: therapeutic implications of INSIGHT. 1283 62

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

This is the third part in a series of papers dealing with various aspects of clinical pharmacology of the first AT(1)-receptor antagonist losartan and its therapeutic use in hypertension, diabetic nephropathy, chronic heart failure, and acute phase of myocardial infarction. This part contains review of literature data concerning the use of losartan for the treatment of chronic heart failure and high risk patients after myocardial infarction. Efficacy and safety of losartan in these conditions was demonstrated in two major randomized trials. In one of these trials effects of the drug were studied in patients with chronic heart failure and in the second one therapy with losartan was started in acute period of myocardial infarction.
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PMID:[Blocker of angiotensin-1 receptor antagonist losartan. Part III. Experience in therapy for chronic heart failure and after acute myocardial infarction]. 1289 Dec 63

This is the second part in a series of papers dealing with various aspects of clinical pharmacology of the first AT1-receptor antagonist losartan and its therapeutic use in hypertension, diabetic nephropathy, chronic heart failure, and acute phase of myocardial infarction. This part contains review of literature data concerning the use of losartan for the treatment of hypertension and diabetic nephropathy including results of two major randomized trials which for the first time demonstrated ability of losartan to improve long term prognosis in patients with hypertension and diabetic nephropathy.
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PMID:[Angiotensin I receptor antagonist losartan. Part II. Effects in arterial hypertension and diabetic nephropathy]. 1289 Dec 78

This is the initial part in a series of papers dealing with various aspects of clinical pharmacology of the first AT(1)-receptor antagonist losartan and its therapeutic use in hypertension, diabetic nephropathy, chronic heart failure, and acute phase of myocardial infarction. Mechanisms of action, pharmacological effects of losartan and other AT(1)-receptor antagonists, as well as data on pharmacokinetics of losartan, its long term tolerability and safety are reviewed in this communication.
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PMID:[Angiotensin1-receptor antagonist losartan. Part I. Basic clinical pharmacology]. 1289 Dec 91

The annual statistical survey conducted at the end of 2000 by the Japanese Society for Dialysis Therapy collected responses from 3358 (99.94%) of 3360 institutions. Japan's total dialysis patient population at the end of the year 2000, as identified by this survey, was 206,134, an increase of 8921 (4.5%) over 1999. This translates to 1624.1 patients per million population. The annual crude mortality rate was 9.4% for the period starting at the end of the year 1999 and ending at the end of the year 2000. The mean patient age at the initiation of dialysis treatment was 63.8 (+/- 13.9; +/- SD) years; the mean age of the overall dialysis patient population was 61.2 years (+/- 13.3). Both these mean ages, which had been increasing since 1983, again continued to increase. Among the primary diagnosis, the prevalence of diabetic nephropathy had continued to increase again since 1999, to 36.6%, whereas that of chronic glomerulonephritis had continued to decline, down to 32.5%, during the same one-year period since the 1999 survey. The 2000 years-end survey incorporated the following additional variables for the first time: usage of oral antihypertensives, pre- and post-dialysis systolic and diastolic blood pressures, serum HDL cholesterol level, types and dosage of oral Vitamin D analogs administered, dosage of oral calcium carbonate administered, history of intervention for peripheral vascular disease (bypass surgery, synthetic graft replacement, stenting), history of coronary artery bypass grafting (CABG), history of percutaneous transluminal coronary angioplasty (PTCA), whether stenting had been previously performed for the treatment of ischemic heart disease, number of cigarettes smoked, the type of vascular access used at the initiation of dialysis, and the year and month the vascular access was created. The survey results indicate that 60.9% of the total dialysis patient population was using oral antihypertensives. The patients' mean serum HDL cholesterol level was 47.65 +/- 18.47 mg/dL, showing positive correlation with serum albumin level and reverse correlation with body mass index. 1.6% of all dialysis patients had previously undergone amputation, and 0.7% had a history of bypass surgery for peripheral vascular disorder. 4.5% of hemodialysis patients had a history of cardiac infarction, 1.6% had previously undergone CABG, and 2.8%, PTCA. At the time the survey was conducted, 2.0% of all dialysis patients were undergoing oral Vitamin D analog pulse therapy, and 6% were undergoing intravenous Vitamin D analog pulse therapy. A history of amputation, myocardial infarction, cerebral infarction, and cerebral bleeding were identified as high-risk factors of vital prognosis. Additionally, high mortality risk was associated with the following: glutamic-pyruvic transaminase levels exceeding 20 IU/L; positive HCV antibody status; comorbid conditions such as hepatic cell carcinoma and liver cirrhosis; platelet counts below 100,000/mL or equal to or greater than 200,000/mL; C-reactive protein levels of 0.2 mg/dL and higher, leukocyte counts of less than 3000/mL or equal to or greater than 8000/mL; and body mass index of below 22 kg/m2, as well as total serum cholesterol levels of below 160 mg/dL or equal to or greater than 260 mg/dL.
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PMID:The current state of chronic dialysis treatment in Japan (as of December 31, 2000). 1292 Nov 11

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