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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) inhibitors have been used in several clinical trials to slow a progressive decline in glomerular function in patients with diabetic nephropathy independent of their effects on blood pressure. The purpose of this study was to clarify the mechanisms(s) through which an ACE inhibitor, captopril, exerts its protective effect on renal function using spontaneously hypertensive rats (SHR) with streptozotocin (STZ)-induced diabetes. Male SHRs were made diabetic by intravenous injection of STZ (45 mg/kg). One hundred or 25 mg/kg of captopril was administered daily for 4 weeks to them. Urine albumin excretion (UAE) rate was markedly increased in diabetic SHRs, while captopril treatment resulted in a significant suppression of UAE in diabetic SHRs, independent of both its daily dose and effects on blood pressure as well as glycemic control. Examination by electron microscope revealed that the number of anionic sites (AS) in the lamina rara externa per 1000 nm of glomerular basement membrane (GBM) was significantly decreased (22.9+/-0.2 to 16.1+/-0.3, p < 0.001), after induction of diabetes, whereas, significant recovery (18.2+/-0.1, p < 0.001) could be obtained even by the smaller dose (25 mg/kg) of captopril which did not exert either antihypertensive or antidiabetic effect on diabetic SHRs. Thus, we demonstrate here the direct evidence that captopril, an ACE inhibitor, can protect against damage on GBM of diabetic SHR without controlling blood pressure as well as blood glucose level.
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PMID:Protective effects of a small dose of captopril on the reduction of glomerular basement membrane anionic sites in spontaneously hypertensive rats with streptozotocin-induced diabetes. 961 73

Diabetic nephropathy (DN) appears in about 30% of patients with type 1 diabetes (D1) and 15 to 60% of patients with type 2 diabetes (D2). It is preceded by microalbuminuria. Microalbuminuria is defined as an albumin excretion rate between 30 and 300 mg/24 h (on a 24-hour urine collection) or between 20 and 200 micrograms/min (on an overnight collection) in at least two out of three consecutive collections made within a 6-month period. Alternative screening techniques use either dipstick (Micral-Test II) or the albumin to creatinine ratio on an early morning urine sample (30-300 mg/g creatinine). Once persistent microalbuminuria is confirmed, 80% of type 1 diabetic patients and 20 to 50% of type 2 diabetic patients will progress to DN. In D2, microalbuminuria also represents a powerful predictor of early mortality from cardiovascular disease. Macroalbuminuria (AER > 300 mg/24 h, corresponding to a total protein excretion > 500 mg/24 h) will eventually lead to a end-stage renal insufficiency within 10 to 20 years. In D2, numerous patients will die from cardiovascular disease before reaching end-stage renal failure. Angiotensin-converting enzyme inhibitors can slow down the evolution toward DN when prescribed when microalbuminuria appears. Screening for microalbuminuria should therefore be a part of the annual clinical assessment in every diabetic patient.
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PMID:[How I evaluate...diabetic nephropathy. First part: micro- and macroalbuminuria]. 981 Feb 12

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

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

Diabetic nephropathy is an important complication of diabetes. Established nephropathy is preceded by a long silent phase of incipient nephropathy characterized by a subclinical increase in albumin excretion know as microalbuminuria (30-300 mg/d). There is evidence that the progression of nephropathy and its associated mortality can be ameliorated by a number of interventions if started at a nearly stage: glycaemic control, that should be optimized as far as possible, and hypertension control. Angiotensin-converting enzyme (ACE) inhibitors are promoted as first-line agent for treating hypertension in diabetic patients; as well as their systemic hypotensive action, these drugs may have an additional beneficial effect in reducing intraglomerular pressure.
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PMID:[Early detection and control of risk factors in diabetic nephropathy]. 988 60

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

Angiotensin I-converting enzyme (ACE) inhibitors are commonly used for the treatment of hypertension, progressive chronic renal disease, diabetic nephropathy, and congestive heart failure. Because angiotensin II acts through membrane bound type 1 (AT1) and type 2 (AT2) receptors, ACE inhibitors and angiotensin II-receptor antagonists have distinct effects. ACE inhibitors inhibit production of angiotensin II thus suppressing the action of angiotensin II on both AT1 and AT2. In contrast, the effect of AT1-receptor antagonists is to selectively block the activation of the AT1 receptor. This AT1-receptor blockade leaves the AT2 receptors unopposed to elevated levels of endogenous angiotensin II. Thus, there may be an advantage of AT1-receptor blockade over ACE inhibition in the management of a variety of chronic vascular diseases, including chronic glomerulonephritis and other glomerular diseases. In a clinical trial candesartan, an AT1-receptor antagonist, effectively lowered urinary protein excretion in patients with chronic glomerular nephritis. Evidence indicates that functionally active AT1 receptors, as well as AT2 receptors, are present in both afferent and efferent arteriole of the glomerulus, and that angiotensin II induces afferent and efferent arteriolar dilatation via AT2 receptors.
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PMID:Effects of candesartan on the proteinuria of chronic glomerulonephritis. 1007 22

Hyperglycemia causes capillary vasodilation and high glomerular capillary hydraulic pressure, which lead to glomerulosclerosis and hypertension in type 1 diabetic subjects. The insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene can modulate risk of nephropathy due to hyperglycemia, and the II genotype (producing low plasma ACE concentrations and probably reduced renal angiotensin II generation and kinin inactivation) may protect against diabetic nephropathy. We tested the possible interaction between ACE I/D polymorphism and uncontrolled type 1 diabetes by measuring glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during normoglycemia ( approximately 5 mmol/L) and hyperglycemia ( approximately 15 mmol/L) in 9 normoalbuminuric, normotensive type 1 diabetic subjects with the II genotype and 18 matched controls with the ID or DD genotype. Baseline GFR (145+/-22 mL/min per 1.73 m2) and ERPF (636+/-69 mL/min per 1.73 m2) of II subjects declined by 8+/-10% and 10+/-9%, respectively, during hyperglycemia; whereas baseline GFR (138+/-16 mL/min per 1.73 m2) and ERPF (607+/-93 mL/min per 1.73 m2) increased by 4+/-7% and 6+/-11%, respectively, in ID and DD subjects (II versus ID or DD subjects: P=0.0007 and P=0.0005, for GFR and ERPF, respectively). The changes in renal hemodynamics of subjects carrying 1 or 2 D alleles were compatible, with a mainly preglomerular vasodilation induced by hyperglycemia, proportional to plasma ACE concentration (P=0.024); this was not observed in subjects with the II genotype. Thus, type 1 diabetic individuals with the II genotype are resistant to glomerular changes induced by hyperglycemia, providing a basis for their reduced risk of nephropathy.
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PMID:Renal changes on hyperglycemia and angiotensin-converting enzyme in type 1 diabetes. 1008 86

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

Angiotensin-converting enzyme inhibitors (ACEi) are a class of antihypertensive agents that decrease mortality in congestive heart failure and have established efficacy in the treatment of hypertension and the slowing of established diabetic nephropathy and other proteinuria-associated glomerulonephritides. These drugs have not gained wide acceptance in the treatment of hypertension in renal transplant recipients (RTRs) because of a potential for decreased renal blood flow and glomerular filtration rate associated with a single kidney and concomitant cyclosporine use. Experimental animal models suggest that ACEi may be of benefit in slowing the progression of chronic renal allograft rejection. We undertook a retrospective chart analysis of all RTRs in our institution who had been treated with an ACEi or an angiotensin II (AT II) antagonist, with the objectives of determining the safety, efficacy, and side effect profile of these medications. The minimum follow-up period was 6 months. One hundred seventy-seven of 642 RTRs were prescribed an ACEi or AT II antagonist. Forty-seven patients discontinued therapy, with the most common causes of discontinuation being cough (8 patients) and hyperkalemia (6 patients). The mean arterial blood pressure at each follow-up period was lower than that at the time of initiation of ACEi or AT II antagonist therapy, with a decrease from 92 +/- 12 mm Hg to 86 +/- 9 mm Hg (P < 0.05) after 3 years of treatment. The serum creatinine concentrations did not change throughout the follow-up period. There was a nonsustained increase from the baseline serum potassium of 4.4 +/- 0.5 to 4.6 +/- 0.6 mEq/L at 3 months (P < 0.05), but no further increases in potassium beyond this time. The mean hemoglobin concentration for the cohort did not change, but 13 RTRs given an ACEi for posttransplantation erythrocytosis (PTE) had a decrease in hemoglobin from 17.1 +/- 1.0 g/dL at the start of ACEi therapy to 14.8 +/- 2.2 g/dL at 3 years (P < 0.05). ACEi and AT II antagonists were generally effective antihypertensives, and were safe and well-tolerated agents in this cohort of RTRs. ACEi were also effective in the treatment of PTE.
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PMID:ACE inhibitors and angiotensin II antagonists in renal transplantation: an analysis of safety and efficacy. 1062 May 59


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