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)

A protective effect of angiotensin-converting enzyme (ACE) inhibitors has been shown in patients with diabetic nephropathy but has not been clearly established in nondiabetic renal disease. A multicenter European study was designed to determine whether the ACE inhibitor benazepril was safe and effective in protecting residual renal function in patients with various renal diseases and mild to moderate renal failure. The trial involved 583 patients from 49 centers in Italy, France, and Germany. The patients were randomized to receive benazepril or placebo plus other antihypertensive agents, the target being a diastolic blood pressure of less than 90 mm Hg. Thirty-one patients in the benazepril group and 57 patients in the placebo group reached the end point [the time elapsed from entry to (a) doubling of serum creatinine (SCr) concentrations and (b) start of renal replacement therapy; p < 0.001 at 3 years]. The associated reduction in the relative risk of reaching the end point was 53% in benazepril-treated patients, with actuarial renal survival probability significantly better at 3 years. The best survival of renal function was observed in patients with chronic glomerular diseases and proteinuria greater than 1.0 g/24 h. Benazepril is effective in slowing the rate of progression and improving the survival of renal function in patients with renal diseases of various origins. This protective effect is associated with a clinically relevant decrease in both blood pressure and proteinuria.
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PMID:Angiotensin-converting enzyme inhibitors and kidney protection: the AIPRI trial. The ACE Inhibition in Progressive Renal Insufficiency (AIPRI) Study Group. 1002 49

Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in diabetic patients. This study tested whether dual blockade of the renin-angiotensin system (RAS) with both an angiotensin-converting enzyme (ACE) inhibitor (ACE-I) and an Angiotensin-II receptor blocker (ARB) is superior to either drug alone in type I diabetic patients with diabetic nephropathy (DN). A randomized double-blind crossover trial was performed with 8-wk treatment with placebo, 20 mg of benazepril once daily, 80 mg of valsartan once daily, and the combination of 20 mg of benazepril and 80 mg of valsartan. Twenty type I diabetic patients with DN were included. At the end of each treatment period, albuminuria, 24-h BP, and GFR were measured. Eighteen patients completed the study. Placebo values were: albuminuria [mean (95% CI)], 701 (490 to 1002) mg/24 h; BP [mean (SEM)], 144 (4)/79 (2) mmHg, and GFR [mean (SEM)], 82 (7) ml/min per 1.73 m(2). Treatment with benazepril, valsartan, or dual blockade significantly reduced albuminuria and BP compared with placebo. Benazepril and valsartan were equally effective. Dual blockade induced an additional reduction in albuminuria of 43 % (29 to 54 %) compared with any type of monotherapy, and a reduction in systolic BP of 6 (0 to 13) mmHg and 7 (1 to 14) mmHg (versus benazepril and valsartan, respectively) and a reduction of 7 (4 to 10) mmHg diastolic compared with both monotherapies. GFR was reversibly reduced on dual blockade compared with monotherapy and placebo. All treatments were safe and well tolerated. In conclusion, dual blockade of the RAS may offer additional renal and cardiovascular protection in type I diabetic patients with DN.
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PMID:Additive effect of ACE inhibition and angiotensin II receptor blockade in type I diabetic patients with diabetic nephropathy. 1266 Mar 33

Plasmin is an important factor in the degradation of extracellular matrix. In the study reported here we examined the expression of plasminogen-activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (uPA), and uPA receptor (uPAR), as well as the relevance of such expression to the production of type IV collagen, a major component of extracellular matrix, in the renal tissue of rats with streptozotocin-induced diabetes. Because angiotensin II is involved in the synthesis of PAI-1 and uPA, we also examined the effect of benazepril, an angiotensin-converting-enzyme inhibitor, on the expression of PAI-1, uPA, and uPAR messenger RNAs (mRNAs) and type IV collagen protein. Rats with streptozocin-induced diabetes-some untreated and some treated with 30 mg/L benazepril-and nondiabetic control rats were sacrificed at 4, 12, or 24 weeks after induction of diabetes. We examined the expression of PAI-1, uPA, and uPAR mRNAs through the use of in situ hybridization and that of type IV collagen by means of immunohistochemical methods. In control rats, we detected weak signals for PAI-1, uPA, and uPAR mRNAs in glomeruli. Diabetic rats exhibited high levels of expression of PAI-1, uPA, and uPAR mRNAs and type IV collagen protein, mainly in mesangial cells. These mRNAs were synthesized in various renal cells (epithelial, mesangial, and endothelial cells and Bowman's capsule). Benazepril inhibited increases in all 3 mRNAs, especially in the mesangium; reduced type IV collagen expression; and attenuated mesangial expansion. Our results indicated that altered expression of PAI-1, uPA, and uPAR in diabetic nephropathy was associated with mesangial expansion and that the beneficial effects of ACE-I may be at least associated with such expression.
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PMID:Renal synthesis of urokinase type-plasminogen activator, its receptor, and plasminogen activator inhibitor-1 in diabetic nephropathy in rats: modulation by angiotensin-converting-enzyme inhibitor. 1532 1

The effects of benazepril on P42/44MAPK, angiotensin II expression in renal tissue and renal pathological change of the experimental diabetic rats were assessed and the possible mechanism of benazepril's renoprotective effect was explored. Adult male Wistar rats, 11-12 weeks age, weighing initially 160 to 200 g were randomly allocated into 2 groups: control group (A, n = 6) and experimental group (n = 12). Diabetic rats in experimental group were rendered diabetic by intraperitoneal injection of Streptozotocin (60 mg/kg body weight), and randomly subdivided into B group (diabetic control) and C group (diabetic rats treated with benazepril, 6 mg/kg every day). Studies were performed 8 weeks after induction of diabetes. Twenty-four h urine of every rat was collected to detect urine creatinine. Serum glucose concentration and serum creatinine were determined by collecting blood samples from the inferior vena cava. Body and kidney weight were recorded. Creatinine clearance (Ccr) and ratio of kidney weight to body weight were calculated. Plasma and renal tissue angiotensin II concentration was assayed by radioimmunoassay (RIA). The phospo-p44/42MAPK protein expression was detected by Western-blot. The results showed that benazepril had no significant effect on the blood glucose level in diabetic rats in two experimental groups. Ccr and ratio of kidney weight to body weight were increased in group B (P < 0.01) as compared with normal rats at the end of the 8th week. At the end of the 8th week, Ccr in group C was lower than that in group B (P < 0.01). The ratio of kidney weight to body weight in group C was lower than that in group B at the 8th week. There were glomeruli hypertrophy and slight or moderate mesangium proliferation in diabetic rats, while there was fragmentally proliferative mesangium in group C at the end of the 8th week. Renal tissue angiotensin II concentration was significantly increased in group B, while benazepril could significantly decrease the concentration of angiotensin II in renal tissue. The expression of the phospo-p44/42MAPK protein in group B was increased as compared with group A, while it was decreased in group C as compared with group B. P42/ 44MAPK pathway participated in the pathogenesis of diabetic nephropathy. Benazepril can eliminate high filtration of glomeruli, decrease proteinuria, and eliminate renal hypertrophy as well as renal destruction. Renoprotective effect of benazepril in diabetic rats may be partly related to the inhibition of angiotensin II -P42/44MAPK pathway.
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PMID:Renoprotective effect of benazepril on diabetic nephropathy mediated by P42/44MAPK. 1593 2

The accumulation of advanced glycation end products (AGE) is a key factor in diabetic nephropathy (DN). Pyridoxamine inhibits AGE formation and protects against type I DN. Herein we tested: (1) whether C57BL6 db/db mice as a model of established type II DN resembled patients treated with drugs which inhibit angiotensin II action; (2) whether pyridoxamine was effective as a single therapy; and (3) whether pyridoxamine would add to the benefit of angiotensin-converting enzyme inhibition (ACEi) by enalapril. In first set of experiments mice were treated with ACEi (benazepril) and an angiotensin II receptor blocker (valsartan) combination for 16 weeks after the onset of diabetes. In second group, mice with established DN were treated with pyridoxamine for 8 weeks. In a third set, mice with established DN were treated with pyridoxamine and enalapril combination for 16 weeks. Benazepril and valsartan combination partially prevented the development and progression of DN. Pyridoxamine treatment, as single therapy, decreased the progression of albuminuria and glomerular lesions. The combination of pyridoxamine with enalapril reduced both mortality and the progression of DN. In conclusion, (1) C57 BL6 db/db mice are a model of progressive type II DN; (2) The combination of pyridoxamine with enalapril decreased progression of type 2 DN and overall mortality. Thus, pyridoxamine could be a valuable adjunct to the current treatment of established type II DN.
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PMID:Combined AGE inhibition and ACEi decreases the progression of established diabetic nephropathy in B6 db/db mice. 1677 96