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)

Captopril given in dosages of 25 mg reduced the doubling of serum creatinine levels by 48% in patients with insulin-dependent diabetes mellitus. Intensive insulin therapy in patients with IDDM delays the onset and slows the progression of diabetic nephropathy, retinopathy, and neuropathy.
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PMID:Nephrology. 775 21

Angiotensin converting enzyme (ACE) inhibitors are now widely used for the treatment of hypertension and heart failure. They are of particular value in treating hypertensive patients with left ventricular dysfunction, and in diabetics where they have been shown to delay the progression of diabetic nephropathy. Differences in the metabolism, pharmacokinetics, and pharmacodynamics between the various ACE inhibitors generally do not translate into significant clinical differences in the majority of patients. However, fosinopril may be the preferred ACE inhibitor in patients with significant renal dysfunction because of a reduced requirement for dosage reduction. The duration of action of ACE inhibitors is determined by two properties, the plasma half-life and the affinity of binding to tissue ACE. All of the ACE inhibitors (with the possible exception of captopril) can provide satisfactory 24-hour blood pressure control in the majority of patients with mild to moderate hypertension when given once daily. Lisinopril provides consistently better 24-hour control of blood pressure than either captopril or enalapril. Evidence for superior 24-hour blood pressure control over enalapril has not been as well established for the other ACE inhibitors. Captopril may be preferred for initiating therapy in patients with severe heart failure who are at risk of first dose hypertension because of its rapid onset of action and relatively short duration of action. There is evidence, however, that perindopril may have a low risk of first dose hypertension in heart failure because of its gradual onset of action. Long-acting ACE inhibitors may be preferable for chronic therapy of heart failure. All of the ACE inhibitors have a low incidence of adverse effects in both young and elderly patients, and there is no convincing evidence of differences in tolerability between the drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Critical assessment of ACE inhibitors. Part 2. 777 72

Antiproteinuria effects of angiotensin-converting enzyme (ACE) inhibitors was studied in 23 patients with chronic nephritis (CN) and 32 patients with diabetic nephropathy (DN). CN patients received Capoten, DN patients were given enalapril. The drugs were also examined for the action on systemic arterial pressure, renal function and intrarenal hemodynamics. Significantly decreased urinary excretion of protein occurred in DN patients on the treatment month 1, in CN subjects on month 3. In both groups ACE inhibitors produced marked hypotensive effect, did not affect renal function, noticeably improved intraglomerular hemodynamics. Hypotensive and antiproteinuria activity of the drugs were unrelated. The mechanism of antiproteinuria action of ACE inhibitors works via normalization of intrarenal hemodynamics. Systemic arterial hypertension seems to be an additional factor aggravating disturbances of intrarenal circulation and provoking proteinuria.
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PMID:[The antiproteinuric action of angiotensin-converting enzyme inhibitors in chronic glomerulonephritis and diabetic nephropathy]. 794 Mar 57

Captopril's short-term effects on clinical and biochemical parameters were studied in 21 diabetic nephropathic patients. Their mean age was 57.50 +/- 2.28 years; 16 of them were women and 5 were men. Eleven patients had been regulated with insulin and 10 of them had been regulated with oral antidiabetics. Fifteen patients were microalbuminuric (200 mg/daily and below albuminuria) and their mean diabetes mellitus history was 14.86 +/- 1.44 years. Six patients had advanced diabetic nephropathy (400 mg/daily and above albuminuria). Their mean diabetes mellitus history was 4.50 +/- 2.87 years. Captopril in a low dose (37.5 mg/daily p.o., three separated doses) was given during 20 days. In the microalbuminuria group there were insignificant alterations in renal function, blood glucose levels, and systolic blood pressure. Diastolic blood pressure decreased significantly in this group (p < .05). Microalbuminuria increased significantly after the therapy in this group (p < .05). In the advanced diabetic nephropathy group, blood glucose and systemic blood pressure levels did not change significantly (p > .05), while serum BUN and creatinine levels increased significantly (p < .05), and GFR decreased significantly in this group (p < .05). Albuminuria decreased after the therapy in this group (p < .05). In all study groups, serum potassium levels increased significantly while serum total protein and albumin levels did not change significantly.We concluded that in the microalbuminuria group, increasing microalbuminuria may be related to a captopril-induced increase in renal plasma flow rate and single nephron glomerular filtration rate. This increase in microalbuminuria cannot be related with blood glucose levels, renal functions, and systemic blood pressure alterations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of angiotensin-converting enzyme inhibitors on the clinical and biochemical parameters in diabetic nephropathy. 829 Jul 8

In 15 type I diabetics with manifest diabetic nephropathy the authors investigated the antihypertensive and antiproteinuric effect of captopril and in seven patients of this group also its effect on renal haemodynamics. Captopril treatment or its combination with hitherto used antihypertensive treatment was associated after two months with a significant drop of the systolic and diastolic blood pressure from 150/95 (120/70-195/110) to 130/90 (110/65-180/115) mmHg, (p < 0.005 < 0.05). The median aortic pressure declined from 118.5 (92-140.8) to 106.5 (84-1334.8) mm Hg (p < 0.005). Nine of 11 patients (82%) could be changed to reduced antihypertensive therapy. The antiproteinuric effect was manifested in 11 patients (73%). Quantitative proteinuria dropped from 2.7 (0.83-8.65) to 1.85 (0.38-8.84) g/24 h., (p < 0.05) without a significant change of serum creatinine: 109 (70-342) vs. 135 (90-288) mumol/l, p = n.s.). The change of proteinuria, as compared with the baseline value, was -41 (-77 - +88)%, (p < 0.05) and did not correlate with the change of the median aortic pressure (correlation coefficient = -0.165, p = n.s.). In the group of seven patients the change of the median aortic pressure was -15% (-26.1 - +6.6), (p < 0.05). No statistically significant change of glomerular filtration was observed: 0.96 (0.32-1.38) vs. 0.96 (0.19-1.71) ml/s, p = n.s.); effective renal plasma flow: 6.32 (2.24-7.74) vs. 7.22 (1.68-10.55) ml/s, (p = n.s.); filtration fraction: 0.136 (0.123-0.220) vs. 0.130 (0.110-0.236), change 0.0 (-43.0 - +31.0)% (p = n.s.) and renal vascular resistance: 15429 (12907-54148) vs. 13243 (7099-77832)%, (p. = n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Changes in blood pressure, proteinuria and renal hemodynamics in type I diabetes with manifestations of diabetic nephropathy after 2 months of captopril therapy]. 834 43

Transforming growth factor beta (TGF-beta) may be important in the pathogenesis of diabetic nephropathy, and captopril is effective in treating this disorder. However, the mechanisms of this therapeutic effect as related to TGF-beta and its receptors are not known. Thus, the effects of captopril on cellular growth, TGF-beta 1, and TGF-beta receptors were studied in LLC-PK1 cells cultured in normal (11 mM) or high glucose (27.5 mM). This study found that glucose dose-dependently inhibited cellular mitogenesis while inducing hypertrophy in these cells at 72 h of culture, concomitantly with enhanced TGF-beta 1 messenger RNA (mRNA) and TGF-beta receptor Types I and II protein expressions. Captopril dose-dependently (0.1 to 10 mM) increased cellular mitogenesis and inhibited hypertrophy in these cells. Moreover, captopril also decreased TGF-beta receptor Types I and II protein expressions dose-dependently. However, TGF-beta 1 mRNA was not affected by captopril. It was concluded that high glucose decreased cellular mitogenesis while increasing hypertrophy concomitantly with increased TGF-beta 1 mRNA and TGF-beta receptors in LLC-PK1 cells. Captopril can reverse high-glucose-induced growth effects by decreasing TGF-beta receptor protein expressions.
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PMID:Captopril reverses high-glucose-induced growth effects on LLC-PK1 cells partly by decreasing transforming growth factor-beta receptor protein expressions. 886 14

ACE-inhibitors are used in the treatment of hypertension, and ischemic heart disease, chronic heart failure, cardiomyopathy and diabetic nephropathy. The effect of the ACE inhibitors is mainly due to the inhibition of the angiotensin converting-enzyme, but they also potentiate the effect of bradykinine. Sargent et al. have indicated, that SH-containing ACE-inhibitors show an effect on KATP-channel open probability in vascular smooth muscle. In our experiments, we used isolated bovine coronary arteries and guinea pig aortas, which were cut transversally and brought into Normal-Tyrode-solution. The vessels were precontracted with phenylephrine or U 46619, and after that a cumulative dose of the SH-containing ACE-inhibitors Captopril or Zofenopril was added to obtain a relaxation curve. In a second series we blocked the KATP-channels with glibenclamide to see if the relaxation could be attenuated. In bovine coronary arteries the relaxing effect of Captopril could not be attenuated by glibenclamide, a specific blocker of KATP-channels of vascular smooth muscle. In the guinea pig aorta, the relaxing effect of Zofenopril was also not effected by glibenclamide. The concentrations of Zofenopril were between 10(-7) and 10(-4) mol/l; the maximal effect could be seen at a concentration of 10(-5) mol/l. Experiments with the non SH-containing ACE-inhibitor Enalapril did also not show any statistically significant difference between the 2 groups of series. We conclude, that, in contrast to Sargent's conclusions, there is little or no effect on KATP-channels due to the presence of SH-groups.
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PMID:[ACE inhibitors with SH groups have no effect of ATP-dependent K channels--a dissertation]. 896 87

One of the mechanisms of angiotensin-converting enzyme inhibitors in treating diabetic nephropathy is the reversal of renal hypertrophy. Hyperglycemia is the common denominator of all diabetic states. Thus, effects of captopril on high glucose (27.5 mM)-induced alterations in LLC-PK1 cells were studied as related to the facilitative glucose transporters. We found that high glucose (27.5 mM) inhibited mitogenesis and induced hypertrophy in these cells after 48 hours of culture concomitantly with decreased glucose transporter I messenger RNA expression. Captopril (1 mM) reversed the above effects concomitantly with enhancement of glucose transporter I and II messenger RNA expressions. We conclude that decreased expression of glucose transporter I may be associated with increased intracellular glucose and the resultant ill effects. Captopril reversed the above high glucose-induced effects partly by enhancing glucose transporter I and II messenger RNA expressions.
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PMID:Captopril reverses high glucose-induced effects on LLC-PK1 cells partly by enhancing facilitative glucose transporter messenger RNA expressions. 909 Apr 58

The beneficial effect of ACE inhibitors on cardiovascular remodelling from hypertension and ischemic disease may be due to the effect of these drugs on the proliferation/cell death balance. We therefore investigated the effect of the addition of captopril in vitro, on the onset of apoptosis in human vascular myocytes, by using a propidium iodide fluorescence analysis and a morphological analysis using the acridine orange technique. Captopril (0.23 mM) caused an increase in apoptotic phenomena that was more than 3. 5-fold than in controls both at the 24th (7.7 vs. 2%) and the 48th h (10.1 vs. 3.8%). The addition of propranolol strengthened the effect on apoptosis. The induction of apoptotic phenomena may be a mechanism by which ACE inhibitors affect cardiovascular remodelling and it might also explain the favorable effect these drugs have on diseases such as IgA nephropathy and diabetic nephropathy.
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PMID:Does captopril have a direct pro-apoptotic effect? 988 29

Diabetic nephropathy is one of the major complications of insulin-dependent diabetes mellitus (IDDM), with proteinuria being the main clinical manifestation of diabetic nephropathy. Most patients who develop overt proteinuria progress to end-stage renal disease (ESRD), usually within 5 to 7 years; ESRD necessitates dialysis or renal transplantation. Although a relationship between blood pressure reduction and delaying of ESRD has been assumed for a long time, only recently has a controlled randomised clinical trial shown that the treatment of diabetic nephropathy with an ACE inhibitor can significantly delay the loss of renal function and, therefore, ESRD. Consistent with the clinical trial on which this economic evaluation was based, the costs and consequences of 2 alternatives were considered: (i) patients subject to blood pressure control with only antihypertensive medication, but without an ACE inhibitor (placebo group) and (ii) patients given ACE inhibitor therapy (captopril group) with similar blood pressure control to the placebo group. This cost-effectiveness analysis was performed from the perspective of the Italian National Health Service [Servizio Sanitario Nazionale (SSN)]. Accordingly, only direct costs related to publicly funded healthcare services were included. The number of dialysis-years avoided (DYA) was the clinical end-point. A 10-year time horizon was considered for the economic evaluation. Captopril therapy was dominant, being at the same time more effective and less costly. The total cost for the captopril alternative during the 10-year period was 21,901,625 Italian lire (L; 1993 values) per patient, while total cost for the placebo alternative was L30,352,590 per patient. Compared with placebo, 20.01 DYA per 100 patients treated were estimated with captopril therapy during the trial period, equivalent to 2.4 months per patient. The robustness of this result was confirmed by sensitivity analysis: for both extremes, captopril remained dominant. This economic evaluation, requested by the Italian Ministry of Health, demonstrated savings in healthcare expenditure with the use of an ACE inhibitor in patients with proteinuria.
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PMID:Economic evaluation of ACE inhibitor treatment of nephropathy in patients with insulin-dependent diabetes mellitus in Italy. 1016 88


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