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

Some evidence suggests that long-term angiotensin-converting enzyme (ACE) inhibition may become less effective, thereby increasing angiotensin II levels, which could be inhibited by the addition of an angiotensin receptor blocker. We conducted a meta-analysis of randomized trials with searches of MEDLINE, EMBASE, and Cochrane databases. Overall, the combination of an ACE inhibitor and an angiotensin receptor blocker reduced ambulatory blood pressure by 4.7/3.0 mm Hg (95% confidence interval [CI], 2.9 to 6.5/1.6 to 4.3) compared with ACE inhibitor monotherapy and 3.8/2.9 mm Hg (2.4 to 5.3/0.4 to 5.4) compared with angiotensin receptor blocker monotherapy. Clinic blood pressure was reduced by 3.8/2.7 mm Hg (0.9 to 6.7/0.8 to 4.6) and 3.7/2.3 mm Hg (0.4 to 6.9/0.2 to 4.4) compared with ACE inhibitor and angiotensin receptor blocker, respectively. However, the majority of these studies used submaximal doses or once-daily dosing of shorter-acting ACE inhibitors and, when a larger dose of shorter-acting ACE inhibitor was given or a longer-acting ACE inhibitor was used, there was generally no additive effect of the angiotensin receptor blocker on blood pressure. Proteinuria was reduced by the combination compared with ACE inhibitor and angiotensin receptor blocker monotherapy, an effect that was independent of blood pressure in several studies, suggesting that the combination could have benefits in proteinuric nephropathies. None of the studies was of sufficient size and duration to determine whether there may be safety concerns. In conclusion, although there is a small additive effect on blood pressure with an ACE inhibitor-angiotensin receptor blocker combination, the routine use of this combination in uncomplicated hypertension is not recommended until more carefully controlled studies are performed.
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PMID:Systematic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension. 1580 63

The major challenge for the treatment of hypertensive patients with type 2 diabetes is to achieve the uniformly recommended blood pressure goal of 130/80 mmHg, and 120/75 mmHg in proteinuric patients. Such low target blood pressure levels require the administration of multiple drugs. Angiotensin receptor blockers and the combination of angiotensin receptor blockers with diuretics fulfil the criteria to lower blood pressure effectively with a placebo-like side-effect profile. Beyond pressure control, clinical prospective trials have documented that it does matter what kind of antihypertensive agent is used to control blood pressure. Large-scale follow-up trials have documented blood pressure independent effects of angiotensin receptor blocker on cardiac [left-ventricular hypertrophy (LVH), congestive heart failure] and renal protection (proteinuria, chronic renal failure). Of note, in these trials, angiotensin receptor blockers have been combined with diuretics, and most of the included patients have been on combination therapy comprising two to four antihypertensive agents. In addition to the combination of an angiotensin receptor blocker with a diuretic, the combination of an angiotensin receptor blocker with an angiotensin-converting enzyme inhibitor appeared to be most effective in reducing proteinuria, attenuating chronic renal failure and treating congestive heart failure.
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PMID:Optimizing therapeutic strategies to achieve renal and cardiovascular risk reduction in diabetic patients with angiotensin receptor blockers. 1583 71

Treatment of high blood pressure is a central element in prevention of cardiovascular diseases. The new classification of hypertension takes into consideration the close association between blood pressure level and cardiovascular risk and designates blood pressure between 140/90 and 130/80 mmHg as high-normal so that blood pressure <140/90 mmHg should always be the goal. The targeted blood pressure levels are also defined by the extent of end-organ damage already present. The therapeutic objective in patients with diabetes mellitus is a blood pressure level of 130/80 mmHg and in patients with kidney disease and proteinuria 125/75 mmHg. The five substance groups of diuretics, beta-blockers, calcium antagonists, ACE inhibitors, and angiotensin receptor blockers are recommended for primary treatment. In addition to the antihypertensive properties, substance-specific effects of ACE inhibitors and angiotensin receptor blockers have been described. Primarily, instead of monotherapy low-dose combination therapy can also be judicious.
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PMID:[New guidelines for treatment of hypertension]. 1583 89

Hypertension and proteinuria are risk factors for renal disease progression. There is clear evidence that pharmacological blockade of the RAS with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) reduces proteinuria and slows down the progression of renal disease in diabetic and non diabetic nephropathies, a beneficial effect not related to blood pressure control. However, not all patients respond similarly to these treatments. Some patients exhibit a significant beneficial response while others do not. The absence of response may be explained by the incomplete blockade of the RAS obtained with ACEI, which are unable to block completely the formation of AII, some generation of AII is produced via other non ACE pathways. In the search of new alternatives that could improve the antiproteinuric and nephroprotective effects of RAS blockers, the association of ACEI and ARB might prove to be useful. ARB produces a complete blockade of the RAS and stimulates the vasodilating and non-proliferative actions of AII via the AT-2 receptor. Furthermore, ACE inhibitors but not ARB; inhibit the metabolism of kinins, which increases the level of bradykinin, a potent vasodilator. Recently, several authors have shown a more marked antiproteinuric effect of the dual blockade of the RAS versus ACEI or ARB alone in spite of a similar effect on blood pressure. A recent study also has demonstrated that this more marked antiproteinuric effect is associated with a less progression of renal disease in primary, non diabetic nephropathies. Furthermore, at least two studies have shown that, treatment with ARB postpones end-stage renal disease and reduces the rate of decline in renal function in patients with type 2 diabetes and nephropathy, but until now, there is not any clear evidence of a superior beneficial effect of dual blockade versus maximal recommended dose of ARB regarding renal progression in type 2 diabetic nephropathy, which is the most frequent cause of end stage renal disease. Long-term clinical trials are needed and encouraged to further establish the significant role of dual blockade in renal protection particularly in diabetic nephropathy.
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PMID:The reno-protective effect of the dual blockade of the renin angiotensin system (RAS). 1585 85

Both the prevalence and incidence of end-stage renal disease have been increasing in the United States over the past two decades. Diabetes and hypertension are the attributable causes for more than three fourths of all new cases of end-stage renal disease. The overwhelming majority of diabetics with nephropathy are hypertensive, and lowering blood pressure is indicated in all patients with chronic kidney disease because of the increased risk for cardiovascular morbidity and mortality. Multiple studies indicate that reaching goal systolic blood pressure in patients with chronic kidney disease generally requires three to four antihypertensive agents. A number of medication combinations can effectively reduce blood pressure in the chronic kidney disease patient. In this regard, adding a calcium channel blocker to an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker helps in reaching goal blood pressure while preserving renal function in both diabetics and nondiabetics with proteinuria.
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PMID:Management of hypertensive chronic kidney disease: role of calcium channel blockers. 1585 98

Increasing number of diabetic patients develop different stages of renal failure. However, often an inappropriate parameter, the serum creatinine is measured as a marker of glomerular function. Calculated glomerular filtration rate or endogenous creatinine clearance are suggested to be used for the estimation of the glomerular function. Important structures preventing proteinuria in the kidney are glomerular basement membrane, podocytes and proximal tubular cells. In diabetes mellitus loss of nephrin of podocytes can play a role in the development of microalbuminuria, and podocyte desquamation may result in the progression to proteinuria. In diabetes mellitus there is an increased formation of advanced glycation endproducts (AGE), of which the only elimination organ is the kidney. The AGE induce proteinuria and atherosclerosis. Therefore, in diabetes mellitus a vicious circle develops due to proteinuria, nephron loss and accumulation of AGE, which play a role in the initiation and progression of diabetic nephropathy and atherosclerosis. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers having antiproteinuric effect may decrease the risk of diabetic nephropathy and atherosclerosis. Improvement of carbohydrate metabolism with a consequential decrease in the formation of AGE is an important contributor to the prevention and treatment of diabetic nephropathy and atherosclerosis.
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PMID:Prevention and treatment of diabetic nephropathy. 1595 73

Glomerular diseases, including diabetes and various forms of glomerulonephritis, account for more than 70% of patients undergoing renal transplantation. Among these patients, more than 40% develop significant proteinuria, and around 15% develop persistent nephrotic syndrome. The most common cause of posttransplantation proteinuria is chronic allograft nephropathy (60%), followed by recurrent (15%) and de novo (10%) glomerulonephritis. Persistent proteinuria is associated with a significantly reduced rate of graft survival but often can be controlled with non-disease-specific therapy including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers with favorable effects on long-term prognosis. Recurrent or de novo glomerulonephritis occurs in 6%-20% of patients overall and is more common in patients transplanted with glomerulonephritic organs. Glomerulonephritis in the allograft is also associated with a reduction in long-term (5-year) graft survival (40% vs 70%). The most common diseases associated with allograft glomerulonephritis and their recurrence rates in transplantation patients are idiopathic focal glomerular sclerosis (20%-30%), IgA nephropathy (25%), membranoproliferative glomerulonephritis (type 1, 25%; type 2, 80%), membranous nephropathy (30%), and hemolytic-uremic syndrome (classic, 10%; atypical, 40%; familial, 60%). This article reviews new developments in the understanding of 3 of these diseases-focal glomerular sclerosis, membranous nephropathy, and hemolytic-uremic syndrome-as they relate to the incidence of recurrence, the effects of recurrence on graft survival, risk factors for recurrence, and management issues for nephrologists caring for patients with renal allografts. Proper donor selection, early diagnosis in high-risk patients, and appropriate management can prolong graft survival and improve long-term outcomes.
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PMID:Recurrent glomerulonephritis in the renal allograft: an update of selected areas. 1598 71

The nephrotic syndrome is characterized by metabolic disorders leading to an increase in circulating lipoproteins levels. Hypertriglyceridemia and hypercholesterolemia in this case may depend on a reduction in triglyceride-rich lipoproteins catabolism and on an increase in hepatic synthesis of Apo B-containing lipoproteins. These alterations are the starting point of a self-maintaining mechanism, which can accelerate the progression of chronic renal failure. Indeed, hyperlipidemia can affect renal function, increase proteinuria and speed glomerulosclerosis, thus determining a higher risk of progression to dialysis. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is the rate-limiting enzyme in cholesterol synthesis from mevalonate and its inhibitors, or statins, can therefore interfere with the above-mentioned consequences of hyperlipidemia. Statins are already well known for their effectiveness on primary cardiovascular prevention, which cannot be explained only through their hypolipemic effect. As far as kidney diseases are concerned, statin therapy has been shown to prevent creatinine clearance decline and to slow renal function loss, particularly in case of proteinuria, and its favorable effect may depend only partially on the attenuation of hyperlipidemia. Statins may therefore confer tissue protection through lipid-independent mechanisms, which can be triggered by other mediators, such as angiotensin receptor blockers. Possible pathways for the protective action of statins, other than any hypocholesterolemic effect, are: cellular apoptosis/proliferation balance, inflammatory cytokines production, and signal transduction regulation. Statins also play a role in the regulation of the inflammatory and immune response, coagulation process, bone turnover, neovascularization, vascular tone, and arterial pressure. In this study, we would like to provide scientific evidences for the pleiotropic effects of statins, which could be the starting point for the development of new therapeutical strategies in different clinical areas.
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PMID:Statins in nephrotic syndrome: a new weapon against tissue injury. 1607 7

Nephrotic syndrome is an important chronic disease in children, characterized by minimal change disease in the majority. Research on pathogenesis has emphasized the importance of T lymphocyte dysregulation and vascular permeability factors that might alter podocyte function and permselectivity. While mutations in genes that encode important podocyte proteins have also been identified, a hypothesis unifying available evidence on pathogenesis is yet to be proposed. Patients with nephrotic syndrome are at risk for life threatening infections and thromboembolic episodes. Long-term effects of persistent hyperlipidaemia and prolonged steroid therapy are increasingly recognized. Remission of proteinuria following corticosteroid therapy has greater prognostic value, in relation to long-term outcome, than the precise renal histology. Prospective studies show that prolonged duration of therapy for the initial episode results in sustained remission and reduced frequency of relapses. Treatment with levamisole, cyclophosphamide, cyclosporine and mycophenolate mofetil is beneficial in a variable proportion of patients with frequent relapses or steroid dependence. The management of steroid-resistant nephrotic syndrome is difficult; most patients failing to achieve remission show progressive renal damage. Calcineurin inhibitors (cyclosporine, tacrolimus) are capable of inducing remission in a significant proportion of patients, but at risk of nephrotoxicity. Reduction of proteinuria is also possible, in children, using angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers. Prospective trials are necessary to identify effective and safe therapies for patients with frequent relapses, steroid dependence and resistance.
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PMID:Nephrotic syndrome in children. 1610 86

Proteinuria indicates future renal and cardiovascular morbidity, and, conversely, its reduction is associated with improved outcome. In a randomized, double-blind trial with parallel group design, the antiproteinuric effect of candesartan at high doses was analyzed. Patients with normal or mildly impaired renal function, protein excretion rate of 1 to 10 g/d, and treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for 3 mo were eligible. After a 4-wk treatment with 16 mg/d candesartan, patients (n = 32) were allocated to double-blind therapy with either 32 or 64 mg/d candesartan for 12 wk (including 4 wk of uptitration), followed again by 4 wk of candesartan 16 mg/d. Proteinuria at study entry was similar in both groups (geometric mean [95% confidence interval (CI)]; 32 mg/d candesartan 2.14 g/d [95% CI, 1.45 to 3.17]; 64 mg/d candesartan 2.54 g/d [95% CI, 1.91 to 3.40]; NS). After the double-blind treatment phase, proteinuria was reduced to 1.42 g/d (0.85 to 2.37) in the 64-mg/d group (P = 0.017), without any change in the 32-mg/d group (2.02 g/d [95% CI, 1.26 to 3.26]). The change in proteinuria differed between the two groups in absolute (P = 0.025) and relative terms (-29 +/- 50 versus -0 +/- 26%; P = 0.012). After downtitration to 16 mg/d candesartan, proteinuria increased again to 2.38 g/d (1.57 to 3.62) in the 64-mg/d group (P = 0.001) but remained unchanged in the 32-mg/d group (2.04 g/d [95% CI, 1.17 to 3.57]; NS). No change in BP was noticed in response to the different doses of candesartan. These data indicate an additive antiproteinuric effect of ultrahigh dose of the angiotensin receptor blocker candesartan compared with standard dose.
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PMID:Additional antiproteinuric effect of ultrahigh dose candesartan: a double-blind, randomized, prospective study. 1612 Aug 21


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