Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix-associated protein with antiadhesive, antiproliferative, and matrix remodeling properties. SPARC gene and protein expression were investigated after subtotal nephrectomy (STNx), a model of noninflammatory progressive renal injury. In addition, the effect of blockade of the renin-angiotensin system by the angiotensin-converting enzyme inhibitor ramipril or by the angiotensin II receptor antagonist valsartan was examined. The STNx rats developed hypertension, proteinuria, and renal impairment. These changes were associated with a 2.4-fold increase in SPARC gene expression in STNx compared with SHAM kidneys (P < 0.001). In situ hybridization revealed increased SPARC mRNA in glomeruli and interstitial cells, as well as de novo expression by tubular epithelial cells at sites of renal injury. Immunofluorescence studies confirmed concordant changes in SPARC protein. Both ramipril and valsartan ameliorated renal injury and significantly reduced SPARC overexpression in the STNx animals. The findings of the present study suggest that SPARC, in the context of its known biological actions, may influence some of the pathological features associated with significant renal mass reduction.
 ...
PMID:Secreted protein acidic and rich in cysteine expression after subtotal nephrectomy and blockade of the renin-angiotensin system. 929 28

Several trials clearly demonstrate the importance of correcting hypertension and proteinuria in slowing chronic renal insufficiency (CRI) progression. The relationship between hypertension and CRI is at least partly the consequence of impaired renal hemodynamics, mainly mediated by the renin-angiotensin system. Two classes of drugs have so far been shown to have an antiproteinuric and renoprotective effect, in addition to their antihypertensive action: ACE inhibitors and calcium-channel blockers (at least the non-dihydropyridines) which also interfere with the actions of angiotensin II. The same should be true for the newest angiotensin II receptor antagonists. To find conclusive evidence about the superior renoprotective effect of ACE inhibitors (or angiotensin II receptor antagonists) or calcium-channel blockers, we need well-designed, prospective, controlled and randomized long-term trials; the pharmacological rationale for combining the two classes of antihypertensive drugs is supported by the clinical need to reach a target blood pressure (120/80 mmHg) in CRI patients with proteinuria.
 ...
PMID:Treatment of hypertension in chronic renal insufficiency. 937 31

Proteinuric renal diseases are associated with excessive renal synthesis of endothelin 1 (ET-1) either in experimental animals or humans. This has been interpreted as an upregulation of ET-1 gene in proximal tubular cells secondary to overreabsorption of an unusual amount of filtered proteins. Here we used a model of chronic proteinuria, passive Heymann nephritis (PHN), to localize the structure of the kidney responsible for excessive ET-1 expression and synthesis and to clarify whether drugs that reduce glomerular protein trafficking modified the distribution of ET-1 mRNA and the corresponding peptide in the kidney. PHN was induced in Sprague-Dawley rats after injection of rabbit anti-Fx1A antibody. Group 1 (n = 5) was untreated, group 2 (n = 5) was given daily the angiotensin-converting enzyme inhibitor lisinopril (40 mg/l) plus the angiotensin II receptor antagonist L-158,809 (50 mg/l) from day 7--when rats were already proteinuric--to month 12. An additional group of normal rats (n = 5) was used as controls. Urinary excretion of ET-1 was significantly increased in PHN rats as compared with controls and normalized by the treatment. By in situ hybridization a weak signal for ET-1 mRNA was detectable in glomeruli, distal tubular segments, and proximal tubules of control kidneys. By contrast, a strong labeling was found in the kidneys of rats with PHN which was mainly localized to proximal tubules and renal interstitium. The pattern of renal ET-1-like immunoreactivity was remarkably consistent with ET-1 mRNA expression. In animals with PHN given the angiotensin II blocking therapy, the urinary excretion of proteins normalized, and the structural integrity of the kidney was well preserved. In the kidney tissue taken from these animals, both ET-1 mRNA and protein staining were quite comparable to controls. These data suggest a link between excessive protein tubular reabsorption and enhanced renal ET-1 in chronic nephropathies and provide a novel explanation for the renoprotective effect in vivo of drugs that, by blocking the biological activity of angiotensin II, reduce glomerular protein traffic and possible deleterious effects of excessive tubular protein overloading.
 ...
PMID:Angiotensin II blockade limits tubular protein overreabsorption and the consequent upregulation of endothelin 1 gene in experimental membranous nephropathy. 956 18

Functional and structural changes of chronic renal allograft failure share similarities with other chronic nephropathies with low nephron number. In models of reduced nephron number, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers prevented proteinuria and retarded renal lesions. This study investigates whether blockade of angiotensin II activity prevented chronic allograft injury in the Fisher 344 --> Lewis rat kidney transplant model, and compares its effect with that of calcium channel blockers, the main antihypertensive agents used in transplant patients to control BP. Transplanted rats received either no treatment (control), the type 1 angiotensin II receptor antagonist losartan, or the calcium channel blocker lacidipine. Rats received cyclosporine for the first 10 d posttransplant to prevent acute rejection. Doses of antihypertensive drugs were adjusted to achieve a comparable level of BP control throughout the study. Awake systolic BP was comparable in animals given losartan or lacidipine during the 6-mo observation period. Daily treatment with losartan but not lacidipine resulted in a significant decrease in the amount of proteinuria, preserved glomerular and tubulointerstitial structure, and improved graft survival compared with corresponding parameters in control untreated rats. GFR, measured as inulin and p-aminohippurate clearances, respectively, in rats surviving the 6-mo follow-up, was numerically but not significantly higher in losartan-treated animals than in all other groups. Thus, at comparable levels of BP control, losartan but not lacidipine effectively protects animals from chronic allograft injury and allows long-term survival.
 ...
PMID:Chronic allograft nephropathy in the rat is improved by angiotensin II receptor blockade but not by calcium channel antagonism. 977 97

During the last few years there has been a renewed interest in blood-pressure (BP)-induced kidney damage, owing to a progressive increase in the incidence and prevalence of hypertension and vascular diseases as a cause of end-stage renal disease (ESRD). The need to prevent ESRD demands continued efforts so as to identify early those people with hypertension who are at risk and to provide them with effective antihypertensive therapy. This review analyses what is needed in terms of surrogate endpoints for monitoring kidney damage and what is known about the impact of antihypertensive treatments in reducing the BP burden on the kidney in non-diabetic subjects. Although glomerular filtration rate (GFR) and proteinuria are useful surrogate endpoints for patients with nephropathy and GFR below or close to the threshold value for renal insufficiency, it is clear that monitoring changes in either GFR or proteinuria does not provide a sensitive endpoint for subjects with the mildest forms of renal disease, e.g. essential hypertensive patients who are at risk of developing kidney damage. In this case microalbuminuria may be useful, although unequivocal evidence demonstrating that microalbuminuria is a risk marker for developing renal insufficiency in non-diabetic renal diseases has not existed until now, and whether a decrease in microalbuminuria is of prognostic significance in patients with essential hypertension remains to be demonstrated. The beneficial effects of the antihypertensive agents on microalbuminuria are also proportional to BP reduction. If a large enough BP reduction is achieved there seem to be, at most, only minimal differences among the antihypertensive drug classes. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have additional beneficial effects on microalbuminuria independent of the BP reduction, owing to their direct role in glomerular haemodynamics. The heterogeneity in the changes in urinary albumin excretion during antihypertensive treatment may be related to the different factors involved in the presence of microalbuminuria or structural end-organ damage, or both.
 ...
PMID:Renal protection by antihypertensive drugs: insights from microalbuminuria studies. 988 2

Losartan is the first orally active angiotensin II receptor type 1 antagonist for a new class of cardiovascular therapeutic agent. Losartan is converted to an active metabolite (E3174) after oral administration in humans and rats. Both losartan and E3174 contribute to the net angiotensin II receptor blockade and produce anti-hypertensive effect. Losartan not only blocks the vasoconstrictive effect of angiotensin II but also inhibits its mitogenic effect; thus losartan is expected to protect against end-organ-damage-related hypertension and chronic heart failure. Unlike angiotensin-coverting-enzyme inhibitor, losartan does not elicit adverse effects of cough and angioneurotic edema by its blockade of angiotensin II receptor. It is also expected to reduce proteinuria in nephropathy. In addition to its blockade of angiotensin II receptor, losartan blocks thromboxane A2 receptor and facilitates excretion of uric acid, although therapeutic importance of these effects are under investigation. In summary, losartan, an angiotensin II type 1 receptor antagonist is a new class of antihypertensive agent and its therapeutic potentials are not merely reduction of blood pressure but total protection from end-organ damage resulting from activation of both the systemic and local renin-angiotensin system.
 ...
PMID:[Pharmacological characteristics and clinical application of losartan, an orally active AT1 angiotensin II receptor antagonist]. 1052 59

The treatment of hypertension and heart failure has evolved in recent years. It may no longer be sufficient to lower blood pressure per se or correct hemodynamics alone in these conditions to achieve optimal long-term outcomes; rather, the effects of drugs on the cellular events and structural alterations that occur in the vasculature, heart, and kidney must be considered. Drugs that target angiotensin II, which include the angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), may protect target organs from damage and thereby improve outcomes. Nevertheless, it remains to be demonstrated whether these agents are more effective in reducing cardiovascular morbidity and mortality in hypertensive patients than conventional treatment with diuretics and beta blockers. In certain subgroups of hypertensive patients, including those with heart failure, type 1 diabetes with proteinuria, or after myocardial infarction with systolic dysfunction, there is compelling evidence for use of ACE inhibitors. The results from animal models and initial clinical studies suggest that ARBs are also highly effective in these patients. Several large-scale clinical studies, comparing the effect of ARBs and other drug classes on morbidity and mortality outcomes, have been initiated to better define the long-term benefit of ARBs in the treatment of hypertension and heart failure.
 ...
PMID:Long-term benefits of angiotensin II blockade: is the consensus changing? 1058 90

The goals of antihypertensive therapy are to lower blood pressure and prevent end-organ damage without side effects, which affect quality of life. The antihypertensive drugs, regardless of class, all lower blood pressure, but they vary in their mechanisms of action, side-effect profiles, suitability for patients with other comorbid conditions, and ability to protect against the long-term sequelae of hypertension. The Sixth Report of the Joint National Committee on Prevention, Evaluation, and Treatment of High Blood Pressure (JNC-VI) recommends diuretics and beta-blockers as first-line therapy for uncomplicated hypertension, with diuretics also being strongly preferred for patients with isolated systolic hypertension or hypertension and heart failure and beta-blockers being strongly preferred for patients who have had a myocardial infarction (MI) and those with hypertension and angina, atrial tachycardia, or atrial fibrillation. Because angiotensin-converting enzyme (ACE) inhibitors have been shown to be cardioprotective and renoprotective in patients with diabetes or impaired left ventricular (LV) function, the JNC-VI recommends them as first-line therapy in patients with diabetes with proteinuria, heart failure, and MI complicated by LV dysfunction. It recommends calcium channel blockers for hypertensive patients with angina, long-acting dihydropyridines for those with isolated systolic hypertension, and the nondihydropyridines for those with atrial tachycardia or fibrillation, diabetes, and proteinuria. The angiotensin II receptor blockers (ARBs) share many of the organ-protective effects of ACE inhibitors when studied in animal models. They are effective in lowering blood pressure and have a very benign side-effect profile; however, these agents have not been available long enough to ascertain their efficacy in protecting against long-term complications.
 ...
PMID:Clinical overview of antihypertensive classes--clinically relevant differences: myths or facts? Based on a presentation by Alan H. Gradman, MD. 1097 60

Proteinuria is one of the major risk factors for renal disease progression in patients with chronic nephropathies. Studies in disease models have helped to delineate mechanisms leading to renal structural damage as a result of persistent dysfunction of the glomerular barrier to proteins, even when the primary immune or non-immune insult to the kidney has ceased. From these preclinical studies, a role for endothelin in proteinuric chronic renal diseases has been suggested, thus providing the rationale for novel therapeutic approaches with endothelin receptor antagonists to maximize renoprotection so far achieved with blockade of the renin-angiotensin system by angiotensin-converting enzyme inhibition or angiotensin II receptor antagonism. Trials are needed to explore this potential area of clinical interest.
 ...
PMID:Research on renal endothelin in proteinuric nephropathies dictates novel strategies to prevent progression. 1119 41

The nephrotic syndrome, caused by glomerulonephritis, diabetes mellitus, or amyloidosis, is still a therapeutic challenge. Newer therapeutic approaches may be sought in the fields of immunosuppression, nonspecific supportive measures, heparinoid administration, and removal of a supposed glomerular basement membrane toxic factor. In immunosuppression, the newer drugs now used in organ transplantation (cyclosporine, tacrolimus, and mycophenolate mofetil) can also be used in the treatment of glomerulonephritis. In nonspecific supportive treatment, angiotensin II receptor antagonists are now used in addition to angiotensin-converting enzyme inhibitors. Positive effects of hydroxymethylglutaryl coenzyme A reductase inhibitors on the nephrotic syndrome have not yet been proven. Cyclooxygenase II inhibitors must be tested but probably have too many renal side effects, similar to those of nonsteroidal anti-inflammatory drugs. Heparinoids or glycosaminoglycans serve as polyanions and thus have protective effects on the negative charge of the glomerular basement membrane. They can now be administered as oral medications. The removal of a supposed glomerular basement membrane toxic factor that induces proteinuria has been attempted for 20 yr and now is usually performed using immunoadsorption. Especially in cases of recurrent nephrotic syndrome after renal transplantation for patients with glomerulonephritis, this approach has been successful in decreasing proteinuria, although in most cases its effect is not lasting but must be continuously renewed.
 ...
PMID:New aspects of the treatment of nephrotic syndrome. 1125 Oct 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>