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)

Angiotensin converting enzyme (ACE) inhibition has shown promising results in diabetic nephropathy, but long-term results on survival are not available. In a cohort of patients receiving antihypertensive treatment predominantly consisting of beta blockers in combination with diuretics, support for an improved survival has been presented. Addition of ACE inhibition to such a combination treatment may be favorable both due to the suggested renoprotective effects of ACE inhibitors and because diuretics activate the renin-angiotensin system. In 10 insulin-dependent diabetic patients with early diabetic nephropathy [urinary albumin excretion rate (UAE) less than 100o micrograms/min], who were receiving continuous therapy with metoprolol and bendroflumethiazide, a double-blind crossover study with four months addition of ramipril 5 mg (Ramace) and placebo was conducted. UAE (radioimmunoassay) and fractional albumin excretion were significantly reduced after the four months of ramipril administration [UAE: 114.1 x/divided by 1.3 (geometric mean x/divided by confidence factor] versus 174.6 x/divided by 1.2 micrograms/min, 2P less than 0.005). Renal plasma flow (clearance of 131I-hippuran) tended to increase [497 +/- 25 (mean +/- SE) vs. 464 +/- 28 ml/min/1.73 m2, 2P = 0.08], while GFR (125I-iothalamate) stayed unchanged (121 +/- 8 vs. 120 +/- 9 ml/min/1.73 m2). Mean arterial pressure during clearance studies fell moderately (95 +/- 3 vs. 101 +/- 1 mm Hg, 2P less than 0.05) and renal resistance was decreased (2P less than 0.03). ACE activity was suppressed in all patients. Twenty-four-hour ambulatory blood pressure measurements were not significantly different after the two periods (daytime averages: 91 +/- 2 vs. 93 +/- 2, nighttime 80 +/- 2 vs. 84 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of ACE inhibition supplementary to beta blockers and diuretics in early diabetic nephropathy. 135 49

1. Streptozotocin diabetes was induced in Wistar-Kyoto rats fed a 50% protein diet. Animals were randomized to receive either the ACE inhibitor ramipril, 1 mg/L in drinking water (n = 7), or no treatment (n = 7) and were studied for 6 months. Blood glucose, body weight and glomerular filtration rate (GFR) were measured at 0, 1, 4, 8 and 16 weeks of diabetes and urinary albumin excretion was measured every 8 weeks. 2. In both groups, GFR increased significantly within 1 week of induction of diabetes (P less than 0.001) and thereafter remained stable. There was no difference in GFR between the treated and untreated groups. 3. Urinary albumin excretion increased progressively in both groups throughout the study. Ramipril treatment reduced albuminuria by approximately 50% at weeks 16 and 24 (P less than 0.01). 4. The amelioration of diabetic albuminuria by ACE inhibition, in the setting of high dietary protein intake, may have important implications for the treatment of human diabetic nephropathy.
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PMID:Ramipril reduces albuminuria in diabetic rats fed a high protein diet. 252 67

To study the effectiveness of ACE-inhibitors in diabetic nephropathy (DN) 12 male and 16 female patients aged 13-21 years with DN having normal blood pressure (BP) were given ramipril (tritace) in a dose 2.5-5 mg/day in the course of 12-24 weeks. Efficacy and safety of the treatment were assessed by changes in albuminuria and proteinuria, BP. Reduction of albuminuria occurred in 19(79.1%) out of 24 patients with microalbuminuria, in 13(54.1%) of them urine excretion of albumin returned to normal levels. All the patients with proteinuria and macroalbuminuria benefited from ramipril therapy because their proteinuria diminished or even disappeared (2 cases). The persistence of the antiproteinuria effect on posttreatment week 12 was 66.6%. Ramipril effect on BP was minimal. It is inferred that ramipril is effective in the treatment of DN at the stage of microalbuminuria and proteinuria in patients with normal BP.
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PMID:[The effectiveness of ramipril in the treatment of diabetic nephropathy in normotensive children and adolescents]. 950 15

Diabetes is a major risk factor for cardiovascular events. Indeed, people with diabetes are 2-4 times more likely to die from cardiovascular causes than individuals without diabetes. Despite evidence to suggest that the burden of cardiovascular disease may be decreasing in Western populations, this trend has not been repeated in diabetic populations. Diabetes is also the most common cause of new-onset end-stage renal disease, blindness and amputations. The growing incidence of diabetes throughout the world, particularly in developing nations, suggests that diabetes-related cardiovascular disease and other chronic cardiovascular diseases will constitute a serious global threat to health and well-being. The HOPE (Heart Outcomes Prevention Evaluation) study was designed to determine if the angiotensin converting enzyme (ACE) inhibitor, ramipril, prevents cardiovascular events in high risk patients. As people with diabetes have a high risk of such events, this group was specified for inclusion and analysis in the HOPE study. The HOPE study was designed to include up to 4,000 people with diabetes and was designed with high power to detect an 18% risk reduction in the diabetic sub group alone. A total of 3,577 individuals with diabetes were randomised to receive either 10 mg of ramipril or placebo. After a period of 4.5 years of follow-up, the group of patients receiving ramipril had a statistically and clinically significant risk reduction of 25% in the primary outcome of myocardial infarction (MI), stroke or cardiovascular (CV) death. This comprises a 37% risk reduction in CV death, a 22% risk reduction in MI, a 33% reduction in stroke and a 24% reduction in all-cause mortality. The MICRO-HOPE (Microalbuminuria, Cardiovascular, and Renal Outcomes) sub study assessed the effect of ramipril on diabetic nephropathy. This was detected by a centrally measured urine albumin:creatinine ratio and confirmed by timed urine collection. Ramipril significantly reduced the risk of overt nephropathy by 22% (P = 0.045), and overt nephropathy, laser therapy or dialysis by 15% (P = 0.05). ACE inhibition with ramipril represents a new macrovascular and microvascular preventive therapy for people with diabetes.
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PMID:Diabetes and the HOPE study: implications for macrovascular and microvascular disease. 1171 57

Drugs that inhibit the renin-angiotensin system (RAS) are of proven benefit in the treatment of hypertension, congestive heart failure, or acute myocardial infarction. In the last decade, several clinical trials have shown that RAS inhibitors also offer significant renoprotection in both diabetic and non-diabetic nephropathy. However, patients with advanced renal insufficiency did not take part in these trials because of the risk of acute renal failure (ARF) and hyperkalemia, and, for the same reason, most physicians do not offer these drugs to patients with impaired renal function. Recently, a post-hoc analysis of the Ramipril Efficacy In Nephropathy (REIN) study which included patients with severe renal insufficiency, showed that RAS inhibition slows glomerular filtration rate (GFR) decline over time and progression to end-stage renal disease (ESRD) in a safe way in patients quite close to ESRD (basal GFR, 10 to 30 ml/min/1.73m2). These beneficial effects have also been shown in the Reduction of Endpoints in NIDDM with the All Antagonist Losartan (RENAAL) study, in patients with type 2 diabetes mellitus, clinical proteinuria, and renal insufficiency, where RAS inhibition therapy significantly reduced the risk of ESRD once doubling of baseline serum creatinine levels had been achieved as compared to non-RAS anti-hypertensive treatment. Thus, these data suggest that RAS inhibition therapy should be given to all patients with proteinuric chronic nephropathy, independently of the level of renal function.
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PMID:Inhibitors of the renin-angiotensin system reduce the rate of GFR decline and end-stage renal disease in patients with severe renal insufficiency. 1224 75

About two thirds of patients on renal replacement therapy irreversibly lose their kidney function because of progressive nephropathies, such as diabetic nephropathy and nondiabetic chronic renal disease. Halting the progression of these patients to end-stage renal disease (ESRD) is instrumental to substantially decrease the need and cost for renal replacement therapy. A large number of experimental studies have demonstrated that chronic nephropathies share common pathogenic mechanisms that contribute to renal disease progression, even independently of the original etiology. Actually, a variety of insults may result in a common pathway of systemic hypertension, increased glomerular pressure and protein ultrafiltration, glomerular and tubular protein overload, chronic inflammation and, ultimately, scarring. Experimental and clinical data converge to indicate that in chronic renal disease increased protein traffic is nephrotoxic, proteinuria predicts disease progression, and proteinuria reduction is renoprotective. Initial clinical trials, mostly in patients with no or mild proteinuria, failed to demonstrate that ACE inhibition therapy is renoprotective in nondiabetic chronic nephropathies. Consistently, meta-analyses based on data generated by these trials failed to detect a specific, blood pressure-independent, renoprotective effect of ACE inhibition therapy. The Ramipril Efficacy In Nephropathy (REIN) study found that ACE inhibitors, by reducing urinary proteins, may contribute to improve the outcome of nondiabetic renal disease, and reduce the risk of progression to ESRD by about 50%. Cumulative meta-analyses, including the REIN study results, confirmed and extended these findings. Thus, well-designed trials in properly selected and carefully monitored study populations continue to be the best approach to test the efficacy of novel treatments. The meta-analyses may help confirming the consistency of these findings and their generalizability to larger cohorts of patients.
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PMID:Proteinuria predicting outcome in renal disease: nondiabetic nephropathies (REIN). 1548 27

Angiotensin receptor blockers (ARBs) were introduced after clinical trials showed angiotensin-converting enzyme inhibitors (ACEIs) to have extensive clinical benefits in a wide range of diseases. Consequently, it has been more difficult for clinical trials to demonstrate similar, enhanced or additive benefits of ARBs. However, ARBs were introduced with the hypothesis that they were likely a more effective method of interrupting the renin-angiotensin system and would result in enhanced outcomes. Clinical trials in high-risk vascular patients (after myocardial infarction), patients with heart failure and patients with nephropathy show the benefits of ACE inhibition. ARBs likely have similar benefits as ACEIs when used after myocardial infarction, in patients with heart failure and for management of diabetic nephropathy. However, ARBs generally remain a second-line treatment because it has been more difficult to demonstrate that ARBs prevent acute vascular events, such as myocardial infarction, together with the greater clinical trial evidence for ACE inhibition. The primary application of ACEIs over ARBs is reflected in the Canadian clinical guidelines for the management of patients with diabetes, hypertension, heart failure and following myocardial infarction. Until the completion of clinical trials, such as the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), that examine whether ARBs have vascular protective properties similar to ACEIs, it is unlikely that the clinical guidelines will change.
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PMID:Have angiotensin receptor blockers lived up to expectations? 1594 Mar 55

Endothelial dysfunction, characterized by impaired nitric oxide activity, constitutes an early step in the pathogenesis of atherosclerotic disease. Prospective studies have shown that impaired endothelium-dependent vasorelaxation and the vasodilatory response of coronary arteries to acetylcholine predict cardiovascular events. Microalbuminuria and estimated glomerular filtration rate, which are both deeply influenced by renal nitric oxide activity, are predictors of cardiovascular outcome and total mortality but develop at a later stage of renal impairment. Endothelial dysfunction reflects early stage renal involvement in the atherosclerotic processes. The Telmisartan versus Ramipril in renal ENdothelium DYsfunction (TRENDY) trial examined endothelial function of the renal vasculature as a therapeutic target in patients with hypertension and type 2 diabetes, but without albuminuria. The rationale was that blockade of the renin-angiotensin system (RAS) is cardio- and renoprotective at later stages of the disease, but the impact of blockade of the RAS at earlier stages of disease is unknown. The results of TRENDY indicate that the endothelial function, as assessed by basal nitric oxide activity, can be improved after RAS blockade. These data complement the results of the Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) trial, which demonstrated that telmisartan and enalapril similarly decelerate the progression of overt diabetic nephropathy. The results of TRENDY are in accordance with the observed changes in peripheral circulation. Endothelium-dependent vasorelaxation could be improved with angiotensin II receptor blockers, but not with diuretics or beta-blockers, in hypertensive patients. Intervention at the beginning of the renal and cardiovascular continuum offers the opportunity to prevent the fatal development towards renal and cardiac failure.
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PMID:Endothelial dysfunction: how can one intervene at the beginning of the cardiovascular continuum? 1660 59

Inhibition of the renin angiotensin aldosterone system (RAAS) produces protective effects on cardio-renal injury in type 2 diabetes. Vasopeptidase inhibitors (VPI) represent a new pharmacological tool, acting by simultaneous inhibition of the RAAS and neutral endopeptidase. We examined the effects of chronic VPI on renal function and morphology in experimental type 2 diabetes as compared to angiotensin converting enzyme inhibition (ACE-I). Zucker diabetic fatty rats aged 13 weeks were treated with either VPI (AVE7688, ZDF-VPI, n = 8) or ACE-I (Ramipril, ZDF-ACE-I, n = 7) or placebo (ZDF, n = 8). Heterozygous rats served as non-diabetic controls (Ctr, n = 8). Both treatments led to a similar decrease in blood pressure. After 10 weeks of treatment, ZDF developed marked albuminuria. The latter was significantly attenuated in ZDF-VPI as compared to ZDF and ZDF-ACE-I. Renal histology revealed a significant expansion in the glomerular tuft area in all ZDF groups. However, expression of glomerular desmin, which has been recognized as a sensitive marker of early podocyte damage, was significantly increased in ZDF as compared to Ctr. Desmin was reduced in ZDF-VPI but not in animals treated with ACE-I. There was a correlation between albumin excretion and desmin-positive glomerular area. In experimental type 2 diabetes, albuminuria correlates to podocyte damage. These hallmarks of diabetic nephropathy are attenuated by VPI to a greater extent than by ACE-I alone. These findings suggest that podocyte damage is an early critical step in the progression of diabetic nephropathy, and that VPI is a promising pharmacological tool in the treatment of diabetic renal disease.
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PMID:Vasopeptidase inhibition attenuates proteinuria and podocyte injury in Zucker diabetic fatty rats. 1733 28

We compared the levels of transforming growth factor beta1 (TGF-beta1), vascular endothelial growth factor (VEGF) and other biochemical parameters in patients with type 1 diabetes mellitus with and without incipient diabetic nephropathy (iDN) and compared them with healthy control subjects. We also measured the effect of 3 and 6 months of ramipril treatment in diabetes patients with iDN. Compared with healthy controls, TGF-beta1 levels were increased in both groups of diabetes patients, whereas VEGF was only elevated in patients with iDN. Ramipril did not have a significant effect on TGF-beta1 or VEGF levels. We observed a significant decrease in microalbuminuria and cystatin C following ramipril treatment. Increased VEGF levels in patients with iDN suggest a role for this cytokine in the pathogenesis of diabetic nephropathy. Cystatin C would make a suitable marker for the screening and assessment of iDN, and for the evaluation of the therapeutic efficacy of drugs.
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PMID:The effect of ramipril therapy on cytokines and parameters of incipient diabetic nephropathy in patients with type 1 diabetes mellitus. 1759 66


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