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

The attainment of adequate renal protection requires strict blood pressure control and a diminution of proteinuria or microalbuminuria to values as near from normalcy as possible. It has been considered that by getting the first, the second could be attained at the same price. Recent data have confirmed that renal protection in hypertensive patients, diabetics or not, requires combination therapy that has to include an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker. A calcium channel blocker can be added to this without renal compromise. A diuretic will also be needed in most cases. Proteinuria will diminish with this combination in particular if up-titration of the drug blocking the effects of angiotensin II is performed. The control of other associated risk factors is also required, in particular smoking and lipids.
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PMID:Renal protection by antihypertensive therapy. 1211 61

This article has three purposes: 1) to summarize recent findings of the Syst-Eur Trial; 2) to provide a short overview of the large trials in hypertension that have compared older with newer drug classes; and 3) to update the results of a meta-regression analysis that addressed the question of: to what extent blood pressure (BP) lowering can explain the findings of recent outcome trials in hypertensive patients or high-risk patients with normotension or hypertension. The Syst-Eur trial showed that in older patients with isolated systolic hypertension, drug treatment starting with a dihydropyridine calcium channel blocker reduced the risk of stroke and of all cardiovascular complications. Furthermore, this treatment regimen improved the prognosis of diabetic patients; reduced the incidence of proteinuria; and prevented dementia, in particular Alzheimer's disease. The pooled evidence from nine recently published actively controlled outcome trials involving 62,605 hypertensive patients proved that calcium channel blockers have the same long-term efficacy and safety as the older drug classes. Compared with diuretics and beta-blockers, calcium channel blockers may offer greater protection against stroke and less protection against myocardial infarction, resulting in similar overall cardiovascular benefit. A meta-regression analysis including 30 trials and 149,407 hypertensive or high-risk patients showed that BP gradients largely accounted for most-if not all-of the differences in outcome. These findings emphasize the desirability of tight BP control. The hypothesis that angiotensin converting enzyme inhibitors or alpha-blockers might influence outcome beyond their BP lowering-effects was not confirmed.
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PMID:Calcium-channel blockade and cardiovascular prognosis: recent evidence from clinical outcome trials. 1212 Oct 11

Diabetic nephropathy is one of the major causes of end-stage renal disease and is often associated with other macrovascular complications such as ischemic heart disease and peripheral vascular disease. Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (AIIR) have both been shown to have a protective effect on the progression of diabetic nephropathy and have thus become the first choice for treatment of hypertension and/or renal involvement in patients with diabetes. However, most of these patients, especially those with type 2 diabetes, require two of more medications in order to reduce their blood pressure to the levels, which have been proposed in recently published consensus papers. These target blood pressure levels are 130/80 mm Hg in diabetic subjects with proteinuria of up to 1 g/day and 125/75 mm Hg in those with proteinuria in excess of 1 g/day. Combinations of different medications may have a synergistic effect. Some of the early studies using a combination of either a nondihydropyridine or a dihydropyridine calcium channel blocker with ACE-I demonstrated a synergistic effect on proteinuria in patients with diabetic nephropathy. However, these studies have not been substantiated, but calcium channel blockers, with their proven ability to reduce blood pressure, play an important role in the treatment of patients with diabetic nephropathy and hypertension. The combination of ACE-I with AIIR may have several theoretical advantages. Many studies using this combination have been performed in animal models of diabetes and in patients with diabetic and nondiabetic renal disease. Some of these studies have demonstrated a synergistic effect of the combination on proteinuria or hypertension, but the results have not been consistent in all studies. It may be concluded that, until additional studies provide more convincing evidence, this combination could be used in patients whose proteinuria or hypertension has not responded to either one of the agents as monotherapy or to a combination of other medications.
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PMID:Combination antihypertensive therapy in the treatment of diabetic nephropathy. 1216 70

Nephrotic syndrome (NS) is frequent in renal transplant recipients and may be related to a large variety of glomerular lesions. In some of these cases, the transplant biopsy showed no significant glomerular changes and the NS was reversible, but the primary renal disease was not minimal change disease (MCD), suggesting that MCD may develop de novo in renal transplant setting. Knowledge of this entity, however, is limited. Among 67 cases of post-transplant NS encountered in a 12-yr period, five were found to be associated with de novo MCD. A critical review of the literature revealed nine additional cases of de novo MCD. The data from these 14 cases show that patients with de novo MCD had a large variety of primary renal diseases but MCD or focal segmental glomerulosclerosis was not among them. Eight of the 14 transplanted kidneys (60%) were from living related donors, suggesting this as a risk factor. Nephrotic range proteinuria (3-76 g/d) developed immediately or shortly after transplantation (within 4 months for all reported cases, except for one at 24 months). The serum creatinine when NS was first diagnosed was normal or mildly elevated, but acute renal failure occurred in three patients. On biopsy, the glomeruli were normal or, more frequently, displayed mild, focal segmental mesangial sclerosis, hypercellularity, deposition of IgM/C3, or accumulation of mononuclear inflammatory cells in some glomerular capillaries. The tubulointerstitial compartment was normal in cases with normal renal function; displayed mild acute and/or chronic rejection that correlated with a mildly elevated serum creatinine; or showed acute changes including acute rejection, acute tubular necrosis, or acute cyclosporin A toxicity, which accounted for both acute renal failure at presentation and its subsequent reversibility. Under various treatments, including increased steroids, angiotensin converting enzyme inhibitors, calcium channel blockers and angiotensin receptor blockers, sustained remission of NS was achieved in 13 cases, within a year (0.5-12 months) in 10 and later (24, 34 and 98 months, respectively) in three. In the remaining case, the patient died of septic shock 2 months after transplantation. After remission of the NS, the grafts functioned well without or with minimal proteinuria for several years. De novo MCD has characteristic clinical and pathologic features. It represents an important but hitherto underemphasized cause of post-transplant NS, which is potentially reversible and does not adversely affect the renal transplants.
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PMID:De novo minimal change disease associated with reversible post-transplant nephrotic syndrome. A report of five cases and review of literature. 1222 32

In an earlier study, we found increased NO production and NO synthase (NOS) expression in renal and vascular tissues of prehypertensive and adult spontaneously hypertensive rats (SHR). This study was designed to determine the effects of aging and AT-1 receptor blockade (losartan 30 mg/kg/day beginning at 8 weeks of age) on NO system in this model. Compared to the Wistar Kyoto (WKY) control rats, untreated SHR showed severe hypertension, elevated urinary NO metabolite (NO(chi)) excretion, marked upregulations of renal and vascular eNOS and iNOS proteins, normal renal function and heart weight at 9 weeks of age. Hypertension control with either AT-1 receptor or calcium channel blockade (felodipine 5 mg/kg/day) mitigated upregulation of NOS isoforms in the young SHR. With advanced age (63 weeks), the untreated SHR showed increased proteinuria, renal insufficiency, cardiomegaly, reduced urinary NO(chi) excretion and depressed renal and vascular NOS protein expressions as compared to the corresponding WKY group. AT-1 receptor blockade prevented proteinuria, renal insufficiency, cardiomegaly, and renal and vascular NOS deficiency. Thus, in young SHR, hypertension results in compensatory upregulation of renal and vascular NOS, which can be attenuated by vigorous antihypertensive therapy. With advanced age, untreated SHR exhibit cardiomegaly, renal dysfunction and marked reductions of eNOS and iNOS compared with the aged WKY rats. Hypertension control with AT-1 receptor blockade initiated early in the course of the disease prevents target organ damage and preserves renal and vascular NOS.
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PMID:Effects of aging and AT-1 receptor blockade on NO synthase expression and renal function in SHR. 1237 78

Important advances in our understanding of the mechanisms and treatment of hypertension in patients at risk for renal disease and those with overt renal disease are taking place. Thus, new data suggest that hyperfiltration may be an important antecedent to the development of kidney disease in hypertensive African-Americans. Also new studies provide evidence for differential responses of endothelial function and sympathetic nerve traffic to ACE inhibitors versus dihydropyridine calcium channel blockers in hypertensives with and without overt renal disease. Important new studies also show that in proteinuric subjects ACE inhibitor treatment is superior to non-ACE treatment at reducing proteinuria and the risk of developing ESRD in non-diabetics with renal disease. In hemodialysis patients, both systolic hypertension and hypotension predict increased mortality in hemodialysis patients. And, identification of factors important in persisting hypertension in patients on hemodialysis provide new insights into improving BP control in this population. The purpose of this review is to highlight the key elements and clinical relevance of these recent studies.
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PMID:Hypertension and kidney literature review 2000. 1240 Aug 39

Experimental studies have demonstrated that proteins filtered by the glomerulus induce a proliferation of proximal tubular cells accompanied by an increased synthesis of many vasoactive and proinflammatory substances. The appearance of interstitial cellular infiltrates, a well-known finding in proteinuric diseases, precedes progressive tubulointerstitial fibrosis. Activation of the transcription factor kappaB (NF-kappaB) plays a pivotal role in the renal damage induced by proteinuria. In this scenario, any therapeutic intervention that reduces proteinuria should be beneficial for the kidney. Drugs that block the renin-angiotensin system [angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA)] have repeatedly shown striking antiproteinuric and renoprotective properties, both in experimental and clinical studies. Studies in patients with type 1 and type 2 diabetic nephropathy as well as in non-diabetic nephropathies have confirmed that the renoprotection obtained with ACEI/ARA is closely related with their antiproteinuric effect and is largely independent of blood pressure changes. However, resistance to the antiproteinuric effect of ACEI/ARA is a common clinical observation. Several therapeutic measures (that is, adequate blood pressure control, early introduction of ACEI/ARA, dietary protein restriction, low salt diets, weight loss in overweight patients, addition of a diuretic, increasing ACEI/ARA dose titrated against proteinuria levels, combined therapy ACEI plus ARA, addition of drugs with antiproteinuric effect such as non-dihydropiridine calcium channel blockers or NSAIDs) may increase the proteinuria reduction induced by ACEI and ARA.
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PMID:Renal damage associated with proteinuria. 1241 Aug 54

In well designed studies in patients with mild to moderate hypertension, combinations of the sustained-release (SR) formulation of the nondihydropyridine calcium channel antagonist verapamil 120 to 240 mg/day and the ACE inhibitor trandolapril 0.5 to 8 mg/day were significantly more effective in reducing sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline than placebo. In most randomised studies, combinations of verapamil SR 120 to 240 mg/day and trandolapril 0.5 to 8 mg/day were significantly more effective in lowering sitting DBP and SBP than the corresponding monotherapies administered at the same dosage. Trandolapril/verapamil SR 2/180 mg/day provided significantly more effective 24-hour ambulatory blood pressure (BP) control than of the corresponding monotherapies. Moreover, trandolapril/verapamil SR reduced BP in patients inadequately controlled with either of the corresponding monotherapies. The antihypertensive efficacy of trandolapril/verapamil SR 2/180 mg/day was generally similar to that of other combinations of antihypertensive agents (metoprolol/hydrochlorothiazide, atenolol/chlorthalidone, lisinopril/hydrochlorothiazide, enalapril/hydrochlorothiazide) in patients with hypertension, including those with type 2 diabetes mellitus. Trandolapril/verapamil SR reduced BP in patients with hypertension and type 2 diabetes or primary renal disease, Black patients and elderly patients. Trandolapril/verapamil SR was more effective than the individual components administered as monotherapy in reducing proteinuria in patients with type 2 diabetes or primary renal disease. Trandolapril/verapamil SR had a neutral or beneficial effect on metabolic parameters (glucose, insulin, lipids) in patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR preserved left ventricular function in patients with heart failure. Fewer cardiac events occurred after therapy with trandolapril/verapamil SR than after trandolapril alone in post-myocardial infarction patients with congestive heart failure. The incidence of adverse events in recipients of trandolapril/verapamil SR was similar to that of the individual components, and that of other combination therapies. In placebo-controlled trials conducted in the US, headache, upper respiratory tract infections, cough, constipation, atrioventricular block (first degree) and dizziness were the most commonly reported adverse events in recipients of combinations of verapamil SR (120 to 240 mg/day) and trandolapril (0.5 to 8 mg/day). In conclusion, the fixed-dose combination of trandolapril/verapamil SR is an effective treatment for patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR tended to be more effective than monotherapy with either verapamil SR or trandolapril, and generally showed antihypertensive efficacy similar to that of other combination antihypertensive therapies. Current data support the use of trandolapril/verapamil SR as an alternative treatment when monotherapy with either agent is not effective. Data from large clinical trials currently being conducted will assist in fully defining the role of trandolapril/verapamil SR as a cardio- and renoprotective agent.
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PMID:Fixed combination trandolapril/verapamil sustained-release: a review of its use in essential hypertension. 1242 Nov 12

The most important factor that prevents the progression of renal damage in diabetes mellitus, beside the improvement of blood glucose control, is tight BP control. The tenet of tight BP control may be defined as the lowest BP level one can accomplish using antihypertensive therapy that is at the same time compatible with the absence of untoward side effects. In fact, both the Framingham Heart Study in nondiabetic normal subjects and the United Kingdom Prospective Diabetes Study in type 2 diabetic patients showed that systolic values as low as 108 to 111 mmHg and diastolic values as low as 70 to 71 mmHg are significantly associated with decreased cardiovascular mortality and morbidity. However, 45 to 50% of the patients with type 2 diabetes mellitus and hypertension have systolic BP levels above 140 mmHg during antihypertensive therapy, particularly when using monotherapy. Thus the issue regarding the choice of which drugs one should use to treat hypertension became critical from a clinical point of view. Pharmaceutical compounds, which inhibit the renin-angiotensin system, have become the first-choice treatment in patients with diabetes mellitus and incipient and advanced renal complications. The present brief review analyzes the effects of calcium channel blockers (CCB) on cardiovascular and renal complications in diabetes mellitus. The review discussed those studies that directly and blindly compared CCB with angiotensin-converting enzyme (ACE) inhibitors and with angiotensin II AT(1) receptor blockers (ARB). Furthermore, size of the population recruited in each trial was used as a criterion of priority in the selection of the reports from the available literature. From the point of view of cardiovascular complications, the results of these studies showed a slightly better benefit of CCB on stroke, whereas ACE inhibitors better prevented the occurrence of myocardial infarction and congestive heart failure. On the other hand, recent observations demonstrated that also ACE inhibitors and ARB are effective in the primary and secondary prevention of stroke, although these studies did not directly compare these compounds with CCB. With regard to the outcome of renal complications, both ARB and ACE inhibitors more effectively prevented the progression of renal damage among the patients with overt nephropathy than CCB. On the contrary, both CCB and ACE inhibitors were equally effective on blunting the decay of GFR in diabetic patients who do not have overt proteinuria. However, ACE inhibitors and ARB more markedly decreased the rate of albumin excretion rate in the range of both microalbuminuria and macroalbuminuria. Recent advances in the understanding of the pathogenesis of abnormalities of albumin excretion rate and of atherosclerosis are also discussed. Both mechanical stress, mainly secondary to systolic hypertension, and elevated circulating and tissue levels of angiotensin II, partially independent from each other, cause excessive generation of superoxide compounds. This chain reaction of events in turn leads to disorders of structural components of glomerular filter and to damage of the vascular wall. Systolic BP control (<130 mmHg) is not adequately accomplished in the majority of the patients treated only with ACE inhibitors and ARB, even in association with diuretics. Poor BP control may lead to excessive systemic mechanical stress at the vascular level despite satisfactory inhibition of angiotensin II effects. In conclusion, one can suggest that CCB are useful and often indispensable pharmaceutical compounds, beside ACE inhibitors and ARB, to accomplish tight BP control (<130/85 mmHg), a target that is unlikely to be successfully maintained in the overall population of type 2 diabetic patients only by ACE inhibitors or ARB, as monotherapy. However, ACE inhibitors and ARB might be considered first-choice drugs in the treatment of hypertension in diabetes mellitus, mainly because of a better renoprotection.
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PMID:Cardiovascular and renal protection in type 2 diabetes mellitus: the role of calcium channel blockers. 1246 17

Diabetic nephropathy is the leading cause of end-stage kidney disease in the United States. The majority of these cases are attributed to those with type 2 diabetes. Elevated blood pressure, proteinuria, and increased activity of the renin-angiotensin-aldosterone system (RAAS) play a major role in the development and progression of chronic kidney disease attributed to diabetes mellitus. Moreover, drugs that inhibit angiotensin II synthesis or block the angiotensin II type I receptor lower blood pressure, reduce proteinuria, and improve outcomes in patients with chronic kidney disease caused by diabetes. This article highlights improvements in the current management of diabetic nephropathy afforded by agents that inhibit the RAAS, discusses their limitations, and considers novel strategies to prevent onset and progression of diabetic nephropathy. Current opinions concerning combination drug therapy with agents that block the RAAS at multiple sites, as well as combining calcium channel blockers with either angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, are also discussed.
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PMID:Appropriate drug therapy for improving outcomes in diabetic nephropathy. 1264 62


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