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)

Microalbuminuria is an established risk factor for renal disease, especially in the diabetic population. Recent studies have shown that microalbuminuria has also a highly relevant predictive value for cardiovascular morbidity and mortality. From normal to overt proteinuria levels, albuminuria shows a continuous marked increase in cardiovascular risk. This association is independent of other "classical" cardiovascular risk factors such as hypertension, hyperlipidemia or smoking. Furthermore it has a predictive value not only for patients with diabetic or renal disease, but also for hypertensive individuals or the general population. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been shown to display not only reno--but also cardioprotective effects. Their unique ability to lower albuminuria by 40% is related to a significant risk reduction in cardiovascular mortality. New clinical trials are needed to define "normal" albuminuria levels and how low we should go.
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PMID:[Microalbuminuria--a new cardiovascular risk factor?]. 1704 69

In recent years, there has been a striking paradigm shift with respect to our understanding of the widespread effects of aldosterone. Whereas the role of angiotensin II in mediating progressive renal disease and heart failure has been documented extensively, more recent evidence has implicated aldosterone as an important pathogenetic factor in addition to angiotensin II in the development of these diseases. The focus of this review is aldosterone and progressive renal dysfunction. The extensive preclinical and clinical evidence supporting the efficacy of aldosterone blockade in abrogating proteinuria is summarized. The frequency and clinical importance of aldosterone "escape" is reviewed. Therapeutic considerations to reduce the incidence of hyperkalemia with aldosterone blockade are discussed. The studies reviewed have several important clinical implications for considering new treatment algorithms for patients with incipient nephropathy. Because full doses of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers attenuate but do not abrogate progression of renal dysfunction, add-on aldosterone blockade therapy may constitute a rational therapeutic strategy for retarding progression of renal disease.
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PMID:Aldosterone blockade: an emerging strategy for abrogating progressive renal disease. 1707 Nov 54

There is clear evidence that pharmacologic blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) reduces proteinuria and slows the progression of renal disease in diabetic and nondiabetic nephropathies, a beneficial effect that is not related to BP control. Some patients exhibit a significant beneficial response, whereas others do not. The absence of response may be explained by the incomplete blockade of the RAS obtained with ACEI. 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 useful. ARB produces a complete blockade of the RAS. Several studies have shown a more marked antiproteinuric effect of the dual blockade of the RAS versus ACEI or ARB alone. A recent study also demonstrated that this more marked antiproteinuric effect is associated with less progression of renal disease in primary nondiabetic nephropathies despite a similar effect on BP. Until now, there has not been any reference to a beneficial effect on progression of the dual blockade in type 2 diabetic nephropathy, which is the most frequent cause of ESRD. A multicenter, prospective, open, active-controlled, and parallel-group trial was designed to compare the effects of an ACE inhibitor versus an ARB or its combination on renal disease progression, proteinuria, and cardiovascular events in type 2 diabetic nephropathy.
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PMID:Dual blockade of the renin-angiotensin system in the progression of renal disease: the need for more clinical trials. 1713 Feb 70

Reducing proteinuria and blood pressure in chronic kidney disease (CKD) decreases rate of progression. Inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers is beneficial in reducing proteinuria but incomplete in suppressing aldosterone production and its renal effects. Adding aldosterone receptor blockers to these other agents may further halt the progression of CKD.
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PMID:Comprehensive suppression of the renin-angiotensin-aldosterone system in chronic kidney disease: covering all of the bases. 1703 49

The current pandemic of diabetes mellitus will inevitably be followed by an epidemic of chronic kidney disease. It is anticipated that 25-40% of patients with type 1 diabetes and 5-40% of patients with type 2 diabetes will ultimately develop diabetic kidney disease. The control of blood pressure represents a key component for the prevention and management of diabetic nephropathy. There is a strong epidemiological connection between hypertension in diabetes and adverse outcomes in diabetes. Hypertension is closely linked to insulin resistance as part of the 'metabolic syndrome'. Diabetic nephropathy may lead to hypertension through direct actions on renal sodium handling, vascular compliance and vasomotor function. Recent clinical trials also support the utility of blood pressure reduction in the prevention of diabetic kidney disease. In patients with normoalbuminuria, transition to microalbuminuria can be prevented by blood pressure reduction. This action appears to be significant regardless of whether patients have elevated blood pressure or not. The efficacy of ACE inhibition appears to be greater than that achieved by other agents with a similar degree of blood pressure reduction; although large observational studies suggest the risk of microalbuminuria may be reduced by blood pressure reduction, regardless of modality. In patients with established microalbuminuria, ACE inhibitors and angiotensin receptor antagonists (angiotensin receptor blockers [ARBs]) consistently reduce the risk of progression from microalbuminuria to macroalbuminuria, over and above their antihypertensive actions. The clinical utility of combining these strategies remains to be established. In patients with overt nephropathy, blood pressure reduction is associated with reduced urinary albumin excretion and, subsequently, a reduced risk of renal impairment or end stage renal disease. In addition to actions on systemic blood pressure, it is now clear that ACE inhibitors and ARBs also reduce proteinuria in patients with diabetes. This anti-proteinuric activity is distinct from other antihypertensive agents and diuretics. Although there is a clear physiological rationale for blockade of the renin angiotensin system, which is strongly supported by clinical studies, to achieve the optimal lowering of blood pressure, particularly in the setting of established diabetic renal disease, a number of different antihypertensive agents will always be needed. In the end, the choice of agents should be individualised to achieve the maximal tolerated reduction in blood pressure and albuminuria. Ultimately, no matter how it is achieved, so long as it is achieved, renal risk can be reduced by agents that lower blood pressure and albuminuria.
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PMID:Blood pressure lowering for the prevention and treatment of diabetic kidney disease. 1713 4

Despite the worldwide epidemic of chronic kidney disease complicating diabetes mellitus, current therapies directed against nephroprogression are limited to angiotensin conversion or receptor blockade. Nonetheless, additional therapeutic possibilities are slowly emerging. The diversity of therapies currently in development reflects the pathogenic complexity of diabetic nephropathy. The three most important candidate drugs currently in development include a glycosaminoglycan, a protein kinase C (PKC) inhibitor and an inhibitor of advanced glycation. In targeting primary mechanisms by which hyperglycaemia contributes to diabetic complications, these drugs could provide risk reduction complementary to the partial reduction proven for ACE inhibitors and angiotensin II receptor antagonists (angiotensin receptor blockers). Glycosaminoglycans act to restore glycoproteins present in reduced amounts in the glomerular basement membrane and mesangium of diabetic animal models. Components of the drug sulodexide prevent pathological changes and proteinuria in diabetic rats. Reductions in albuminuria, a hallmark of early diabetic kidney disease, have been reported in initial human trials. In the US, a multicentre phase II study has been completed, with an interim analysis indicating reduction in urinary albumin losses. Pivotal phase II trials have begun in patients with type 2 diabetes. A second metabolic pathway of diabetic complications is overexpression of PKC. Several activators of this family of intracellular kinases have been identified and PKC activation may result in tissue damage through a variety of mechanisms. In animal models, the inhibitor ruboxistaurin reduces albuminuria, diabetic histological changes and kidney injury. Like sulodexide, drug development of ruboxistaurin has reached completion of a phase II evaluation with mixed results. The third metabolic target is the nonenzymatic formulation of advanced glycation end-products (AGEs) through well described biochemical pathways. Multiple pathways lead to AGE accumulation in tissues in diabetes and diverse AGE products are formed. AGE deposition has been implicated in animal models of diabetic nephropathy. The leading AGE inhibitor currently in development is pyridoxamine, which has multiple actions that inhibit glycation. Pyridoxamine is an efficient AGE inhibitor in experimental diabetes. A phase II study in diabetic patients with nephropathy reported mixed efficacy results and a favourable safety profile. Phase III evaluation of pyridoxamine has not begun. These three classes of potential therapies, if successfully developed, will confirm that diabetic kidney disease has entered the era of biochemical treatments.
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PMID:New potential agents in treating diabetic kidney disease: the fourth act. 1718 72

The presence of proteinuria is a well-known risk factor for both the progression of renal disease and cardiovascular morbidity and mortality, and decreases in urine protein excretion level were associated with a slower decrease in renal function and decrease in risk of cardiovascular events. Increased blood pressure has a major role in the development of proteinuria in patients with either diabetic or nondiabetic kidney disease, and all recent guidelines recommend a blood pressure goal less than 130/80 mm Hg in patients with proteinuria to achieve maximal renal and cardiovascular protection. Drugs interfering with the renin-angiotensin system, ie, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, should be used as first-line antihypertensive therapy in patients with proteinuria because they seem to have a blood pressure-independent antiproteinuric effect, and if blood pressure levels are still out of goal, a diuretic should be added to this regimen. A combination of an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker or other classes of medications shown to decrease protein excretion, such as nondihydropyridine calcium antagonists or aldosterone receptor blockers, should be considered to decrease proteinuria further. This review provides an extended summary of current evidence regarding the associations of blood pressure with proteinuria, the rationale for currently recommended blood pressure goals, and the use of various classes of antihypertensive agents in proteinuric patients.
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PMID:Antihypertensive therapy in the presence of proteinuria. 1718 42

Effective management of diabetic patients includes comprehensive control for not only blood sugar, but also other cardiovascular risk factors. We assessed whether haemoglobin A1c (A1C) concentrations, blood pressure, low density lipoprotein (LDL) cholesterol levels and microalbuminuria were regularly measured in 281 patients with type 2 diabetes who received care for over 1 year in the Department of Family Medicine located in an urban area of Korea. Subsequently, in patients with A1C > 7%; blood pressure >130/80 mmHg; LDL cholesterol levels >100 mg/dl; or microalbuminuria, we evaluated the status of management for those cardiovascular risk factors. Physicians were most likely to measure A1C levels (98.6%), but less likely to measure microalbuminuria (56.2%), LDL cholesterol (73.7%), or blood pressure (74.4%). Patients whose A1C levels were above the goal (78.2%) were likely to receive optimal therapy. In contrast, only 21.1% of patients with uncontrolled blood pressure and 5.3% of patients with LDL cholesterol levels above the target range received optimal management. Of the 36 patients with microalbuminuria or overt proteinuria, 66.7% took angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Measurement of parameters indicating cardiovascular risk factors in type 2 diabetic patients was not optimal, particularly regular measurements for microalbuminuria and for controlling LDL-cholesterol and blood pressure. These findings indicate a need for greater education of comprehensive cardiovascular management in type 2 diabetic patients and their physicians.
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PMID:Lack of management of cardiovascular risk factors in type 2 diabetic patients. 1722 79

Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by various combinations of myoclonus epilepsy, ataxia, choreoathetosis and dementia. No specific therapy has been established and renal complication is rare. We report two cases of DRPLA with renal complications. Hematuria and proteinuria had gradually progressed for 2 and 13 years in these patients. Renal biopsy findings revealed focal glomerulosclerosis in one case and end-stage kidney disease in the other case. Angiotensin-converting enzyme inhibitor and angiotensin receptor II antagonist were administered to both patients, resulting in improved proteinuria and preserved renal function in one patient, while renal function continued to deteriorate in the other patient. Although renal complication is rare in patients with DRPLA, the presence of renal disease has to be suspected in patients with persistent proteinuria.
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PMID:Renal complications in two patients with dentatorubral-pallidoluysian atrophy. 1726 99

In Australia the number of patients developing end-stage kidney disease is growing. Almost 70% of new cases of treated end-stage kidney disease are due to diabetes, hypertension or glomerulonephritis. The majority of these patients have a chronic decline of renal function over many years before dialysis is required, even when the initial insult is no longer present. Hypertension and the degree of proteinuria are the most important determinants for this progression and ample evidence suggests that angiotensin II is the key player in sustaining both hypertension and proteinuria. Angiotensin II mediates not only haemodynamic changes but also profibrotic and pro-inflammatory processes. Blockade of the renin-angiotensin system decreases proteinuria and slows the progression of both diabetic and non-diabetic proteinuric renal disease. Angiotensin-converting enzyme (ACE) inhibitors are first-line therapy in patients with type 1 diabetes mellitus and nephropathy, whereas angiotensin receptor blockers (ARB) are first-line therapy in patients with type 2 diabetes mellitus and microalbuminuria or overt nephropathy. Finally, treatment with ACE inhibitors delays the progression of proteinuric nephropathy in non-diabetic patients. Combination therapy with ACE inhibitors and ARB may allow a more complete blockade of the renin-angiotensin system and clinical trials show that ACE inhibitor-ARB combinations have an additive antiproteinuric effect of up to 40% compared with ACE inhibitor or ARB alone, without additional blood pressure-lowering effect. Finally, it is important to emphasize that progressive lowering of blood pressure to 120 mmHg is associated with improved renal outcome and that this effect is independent of baseline renal function.
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PMID:Prescribing angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in chronic kidney disease. 1729 66


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