UMLS:C0033687 - FACTA Search

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Query: UMLS:C0033687 (proteinuria)
24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study compared the cardiovascular and renal effects of long-term telmisartan (3 and 10 mg/kg/day)and lisinopril (10 mg/kg/day) in an animal model combining hypertension and diabetes mellitus. It was a parallel-group study of diabetic, spontaneously hypertensive rats (SHR), treated with control or active treatment for eight months. A non-diabetic SHR control group was run in parallel. Diabetes was induced by streptozotocin (45 mg/kg i.v.) in SHRs aged 9-10 weeks. Animals were treated with telmisartan (3 or 10mg/kg/day), lisinopril (10 mg/kg/day) or vehicle. Plasma glucose levels, blood pressure (BP), and urinary protein and albumin excretion were measured monthly. Telmisartan treatment significantly reduced BP of diabetic SHRs in a dose-dependent manner (p<0.05, low-dose, n= 18; p<0.01, high-dose, n=15). The BP reduction in the lisinopril group was similar to that in the telmisartan 10 mg/kg/day group. Compared with non-diabetic SHRs, untreated diabetic SHRs developed severe proteinuria and albuminuria over the experimental period (p<0.01). In diabetic SHRs, proteinuria and albuminuria were dose-dependently and significantly attenuated by treatment with telmisartan (p<0.01 with the higher dose) and lisinopril (p<0.01). Compared with the untreated diabetic SHRs, cardiac hypertrophy was significantly reduced after treatment with both doses of telmisartan and with lisinopril. Telmisartan, 10 mg/kg/day, but not lisinopril, significantly attenuated the diabetes-induced increase in glomerular volume. In conclusion, telmisartan, 10 mg/kg/day, is at least as beneficial as lisinopril, 10 mg/kg/day, in lowering BP, reducing cardiac hypertrophy and attenuating renal excretion of protein and albumin in this model.
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PMID:Comparative antihypertensive and renoprotective effects of telmisartan and lisinopril after long-term treatment in hypertensive diabetic rats. 1188 Oct 63

Telmisartan is a type 1 angiotensin II (AT(1)) receptor blocker, effective and safe in the treatment of arterial hypertension. However, data with respect to circadian blood pressure (BP) monitoring and urinary protein (uP) excretion are lacking in normotensive or mild hypertensive patients with chronic renal diseases. This study has evaluated the effects of 80 mg telmisartan, given as monotherapy, on 24 h BP levels and uP loss in 16 non-diabetic patients affected by proteinuric renal disease. These patients did not meet the recommended values of mean BP, i.e. < 98 mmHg, when proteinuria was 0.5-1.0 g/d and mean BP < 92 mmHg, when proteinuria was 1-3 g/d. Patients with diastolic BP > 114 mmHg, nephrotic syndrome or severe renal failure (creatinine clearance < 20 ml/min) were excluded. After 4.2 +/- 2.7 month therapy, ambulatory BP monitoring showed a significant decrease (P < 0.001) of 24 h BP levels: systolic 135 +/- 11 vs. 122 +/- 13 mmHg, diastolic 84.4 +/- 8.1 vs. 75.9 +/- 8.5 mmHg, mean 101 +/- 8 vs. 91 +/- 9 mmHg. The effect was quite evident during either day-time or night-time. Clinic BP levels also significantly decreased (P < 0.001), and five patients reached the target values. uP excretion lowered by 37% (median) from 1.60 +/- 0.90 to 1.06 +/- 0.63 g/24 h (P < 0.01). No change in creatinine clearance (53.3 +/- 31.1 vs. 51.7 +/- 30.9 ml/min) or serum potassium level (4.3 +/- 0.3 vs. 4.4 +/- 0.4 mEq/l) was observed. Our results show that 80 mg of telmisartan, taken once daily, is effective in reducing uP excretion and BP throughout the 24 h, in normotensive or mild hypertensive renal patients. Since evidence exists that adequate control of BP, including during night-time, and reduction of proteinuria play a crucial role in the protection of renal function, telmisartan can be usefully considered in the conservative treatment of renal patients.
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PMID:Effect of telmisartan on the proteinuria and circadian blood pressure profile in chronic renal patients. 1281 79

Fifteen adult male spontaneously hypertensive rats (one year old) (SHR) were separated into three groups (n=5 each) during 15 weeks as follows: initial control group (IC); final control group (FC); and telmisartan group (T) (1.2 mg/kg/day of telmisartan). Serum and urinary creatinine and proteinuria were not different comparing untreated and telmisartan-treated SHRs. FC rats showed a continuous BP increase during the study while T rats reached the 15th week with a significantly low BP. The LV mass index was significantly smaller in the T group than in the FC group, as was the glomerular hypertrophy. The cardiomyocyte nuclei density per area and the cardiomyocyte mean cross-sectional area were smaller in the T group than in both the IC and FC groups. Intramyocardial artery densities (per area and per volume) were greater in the T group than in untreated SHRs, but myocardial fibrosis was reduced. In conclusion, telmisartan monotherapy effects on BP and also on the hypertension target organs, heart and kidney, are favorable. Telmisartan is able to attenuate SHR cardiomyocyte and glomerular hypertrophies, and myocardial reactive fibrosis as well. It also is favorable to the intramyocardial microcirculation.
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PMID:Effect of telmisartan on preexistent cardiac and renal lesions in spontaneously hypertensive mature rats. 1516 34

The primary aim of this study was evaluation of the efficacy of telmisartan (angiotensin II receptor blocker- AT(1) blocker) on blood pressure in 10 patients with renal impairment in moderate or advanced stages of renal insufficiency and not dependent on haemodialysis. Its effect on proteinuria, renal function (represented by serum urea, creatinine, glomerular filtration), evaluation of overall therapy compliance in comparison with a previously prescribed angiotensin converting enzyme inhibitors (ACEI) were secondary aims. Considering the presence of left ventricle hypertrophy in all patients as a marker of hypertensive cardiopathy, the effect of telmisartan therapy on non-invasive cardiovascular parameters (ECG, echocardiography, and assessment of heart rate variability-HRV) was also evaluated. The study group involved 10 hypertensive patients (6 women, 4 men) with diabetic and non-diabetic renal impairment, proteinuria above 1 g/24 hours, hypertensive cardiopathy and intolerance of ACEI (cough). Telmisartan was added to their long-term antihypertensive combination therapy in a dose of 40 mg for the first 14 days, after which the dose increased to the maximal of 80 mg. The average initial daytime systolic blood pressure (SBP) was 149 +/- 19.7 mm Hg, average night-time SBP 145 +/- 23.0 mm Hg, average initial daytime diastolic BP (DBP) 90.6 +/- 2.5 mm Hg, night-time DBP 88.9 +/- 13.5 mm Hg. Average initial serum creatinine was 207.2 +/- 48.5 micromol/l, urea 15.1 +/- 4.4 mmol/l, GF 0.5 +/- 0.1 ml/s. Echocardiography revealed left ventricular (LV) hypertrophy with well preserved systolic and moderately impaired diastolic LV function. Also the HRV assessment revealed impaired neurovegetative (e.g. sympathovagal) balance. After 1 year of combination therapy with telmisartan, there was a clearly significant reduction in both SBP and DBP in both day and night-time (SBP daytime 149.6 vs.116.6 mm Hg, night-time 145.8 vs. 129.5 mm Hg; DBP daytime 90.6 vs. 83.5 mm Hg, night-time 88.9 vs. 79.3 mm Hg) and proteinuria (2.37 vs. 1.27 g/24 hour, p < 0.05). There were no significant changes in serum creatinine, urea values, and LV functions. On the other hand, further progression of the sympathovagal balance impairment was noted (continuing reduction of HRV in 9 from 10 patients), which can be described as the priority finding. The total compliance of telmisartan therapy was very good and without adverse clinical side effects. In conclusion - telmisartan reduces blood pressure and proteinuria safely and effectively in patients with various types of nephropathy in moderate or advanced stages of renal insufficiency.
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PMID:Telmisartan in the treatment of hypertension in patients with chronic renal insufficiency. 1552 50

A progressive chain of pathophysiological events links cardiovascular risk factors to clinical manifestations of disease and life-threatening cardiovascular events. This chain--the cardiovascular continuum--underlies cardiovascular disease and holds the key to its prevention and treatment. Progressive tissue damage can result in morbidity from congestive heart failure, end-stage heart disease, nephrotic proteinuria and dementia and, eventually, death from cardio- or cerebrovascular causes. The renin-angiotensin-aldosterone system (RAAS) is involved at all stages of the cardiovascular continuum, because the effector molecules of the RAAS, angiotensin II in particular, have direct pathobiological effects on a variety of tissues, including the endothelium, vascular smooth muscle and the renal mesangium. Clinical trials of angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors have demonstrated the essential validity of this hypothesis. Interruption of the RAAS has been shown to reduce cardiovascular morbidity and mortality in patients with left ventricular hypertrophy, heart failure and post-myocardial infarction, as well as renal disease in patients with type 2 diabetes. Key questions remain, however. What are the clinical effects of combination ARB and ACE inhibitor treatment? How will combinations of RAAS blockade with other agents, such as statins, affect the cardiovascular continuum? Answers to these questions will require well-planned, adequately powered clinical trials, such as the Programme of Research tO evaluate Telmisartan End-organ proteCTION (PROTECTION) and the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) programmes. However, it is already clear that RAAS blockade is an essential part of blocking progression along the cardiovascular continuum.
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PMID:The cardiovascular continuum and renin-angiotensin-aldosterone system blockade. 1582 52

Diabetic nephropathy is characterised by hypertension and persistent proteinuria. If ineffectively controlled, a progressive decline in renal function can result in end-stage renal disease. Patients with diabetic nephropathy are also at greatly increased risk of cardiovascular disease. Angiotensin-converting enzyme (ACE) inhibitors display additional renoprotective effects beyond systemic blood pressure lowering, perhaps due to reduction in intraglomerular pressure by inhibition of angiotensin II activity. In type 2 diabetics, ACE inhibitors have variable effects, with some studies showing a reduction in microalbuminuria, prevention of the progression to macroalbuminuria and maintenance of renal function. Randomised studies have demonstrated that angiotensin II receptor blockers (ARBs), as well as controlling systemic blood pressure, delay progression of proteinuria in patients with diabetic nephropathy. Telmisartan has a number of features that may make it particularly suitable for the treatment of diabetic nephropathy. In addition to its long duration of action and almost exclusive faecal excretion, its high lipophilicity should assist in tissue penetration. The Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) study was designed to compare the long-term renal outcome of treatment with telmisartan 40.80 mg versus enalapril 10.20 mg (with titration to the higher dose after 4 weeks) in patients with type 2 diabetes, mild-to-moderate hypertension and albuminuria. The primary endpoint is the change in glomerular filtration rate after 5 years' randomised treatment. Secondary endpoints are annual changes in glomerular filtration rate, serum creatinine and urinary albumin excretion, as well as incidences of end-stage renal disease, cardiovascular events, all-cause mortality and adverse events. The groundbreaking DETAIL study revealed that telmisartan conferred comparable renoprotection to enalapril and was associated with a low incidence of mortality.
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PMID:Preventing renal complications in diabetic patients: the Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) study. 1586 19

Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin-angiotensin system (RAS), has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB) and/or angiotensin-converting enzyme (ACE) inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) Programme is expected to provide the ultimate evidence of whether improved endothelial function translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade). Completion of ONTARGET is expected in 2008.
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PMID:Cardiovascular risk reduction by reversing endothelial dysfunction: ARBs, ACE inhibitors, or both? Expectations from the ONTARGET Trial Programme. 1758 70

The purpose of the present study was to investigate the renoprotective effect of telmisartan, an angiotensin II receptor antagonist, on the early stages of diabetic nephropathy in obese Zucker rats, which is a type 2-related diabetes mellitus model. Telmisartan 1, 3 or 10 mg/kg/day was orally administered to 7-week-old rats that demonstrated glucose tolerance without albuminuria or proteinuria, for 24 consecutive weeks (Experiment A). In another experiment (Experiment B), oral administration of telmisartan 10 mg/kg/day was initiated at the age of 16 weeks after the rats demonstrated marked proteinuria, and continued for 24 weeks. Telmisartan inhibited the increase in proteinuria and albuminuria in a dose-dependent manner, and the inhibition for all telmisartan groups was statistically significant by the completion of administration (Experiment A). Telmisartan also displayed similar inhibitory effects on proteinuria and albuminuria in Experiment B. Histologically, telmisartan [3 and 10 mg/kg/day] was associated with a significant decrease in the progression of glomerulosclerosis, and significantly improved interstitial cell infiltration, interstitial fibrosis and dilation and atrophy of renal tubules. Furthermore, telmisartan treatment was associated with a tendency towards normalized plasma lipids (total cholesterol and triglyceride). Our results suggest that telmisartan has a definite renoprotective effect against renal injury in type II diabetic nephropathy.
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PMID:Renoprotective effects of telmisartan on renal injury in obese Zucker rats. 1800 27

Renal pathophysiology is elicited by activation of angiotensin II type 1 (AT(1)) receptors at all stages of renovascular disease. Angiotensin receptor blockers (ARBs) that specifically block the AT(1) receptor offer the potential to prevent or delay progression to end-stage renal disease independently of reductions in blood pressure. Proteinuria--an early and sensitive marker for progressive renal dysfunction--is reduced by ARB use in patients with type 2 diabetic nephropathy and microalbuminuria or macroalbuminuria. Retrospective analysis of data available from early trials has confirmed this finding and has shown that albuminuria reduction is associated with lessening of cardiovascular risk. The ARB telmisartan is equivalent to enalapril in preventing glomerular filtration rate decline, and equivalent to valsartan in reducing proteinuria. Telmisartan is more effective than conventional therapy in lowering the risk of transition to overt nephropathy in hypertensive and normotensive patients. An additive effect has been seen in smaller studies when telmisartan has been added to lisinopril therapy, and high-dose telmisartan reduces albuminuria better than low-dose telmisartan. Similar data were obtained with other ARBs such as candesartan, losartan, valsartan, or irbesartan. These data support the proposition that blockade of the renin-angiotensin system beyond that required for maximum blood pressure reduction provides optimum renal protection.
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PMID:Reduction of proteinuria with angiotensin receptor blockers. 1858 Aug 65

Although the activation of the renin-angiotensin system has a major role in the development of chronic renal failure, little is known about the effect of angiotensin receptor blockers on tubulointerstitial injury. To evaluate the renoprotective effect of telmisartan, we measured urinary protein excretion, urinary liver-type fatty acid binding protein (L-FABP) excretion, and urinary collagen IV in 30 hypertensive patients with chronic kidney disease (CKD). These patients were randomly assigned to receive 40 mg/day (n = 15) or 80 mg/day (n = 15) of telmisartan before the initiation of treatment and 6 and 12 months after treatment. Both doses of telmisartan reduced systolic and diastolic blood pressure after 6 (p < 0.001) and 12 (p < 0.001) months compared with baseline levels. Blood pressure reduction rate were similar between both doses. Urinary protein, urinary L-FABP excretion, and urinary collagen IV levels declined significantly 6 (p < 0.001) and 12 (p < 0.001) months after telmisartan treatment in both doses. The reduction rate in parameters was more pronounced in patients receiving 80 mg/day compared with those taking 40 mg/day telmisartan at 12 months (p < 0.001). Telmisartan reduces proteinuria, urinary L-FABP excretion, and urinary collagen IV levels in hypertensive CKD patients.
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PMID:Renoprotective effect of telmisartan in patients with chronic kidney disease. 1885 69

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