UMLS:C0033687 - FACTA Search

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)

Arterial hypertension together with proteinuria is one of the most important factors associated with the progression of both diabetic and nondiabetic chronic kidney disease. In this review, the role of hypertension and proteinuria in renal disease progression, the BP target that should be achieved to slow the progression of renal damage, and the influence of baseline and current proteinuria on the renoprotective effects of antihypertensive therapy are discussed thoroughly. The interaction between the renoprotective effects of specific antihypertensive agents--mostly angiotensin-converting enzyme inhibitors and angiotensin receptor blockers--and the level of achieved BP also are evaluated. The body of evidence provided by several studies emphasizes the importance of both lowering BP and inhibiting the renin-angiotensin system as specific goals for renal and cardiovascular protection in chronic kidney disease.
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PMID:Importance of blood pressure control in chronic kidney disease. 1656 57

Hypertension is defined by the Joint National Committee (JNC 7) as blood pressure (BP) > or =Y130/80 mmHg. It affects up to 70% of patients with type 2 diabetes and is twice as prevalent in diabetics as in non-diabetics. Due to its contribution to renal and cardiovascular disease, hypertension increases diabetic mortality four to five-fold. Therefore, a BP goal of 130/80 mmHg or less (125/75 mmHg in patients with proteinuria >1 g/die and increased creatinemia), is recommended. For isolated systolic hypertension, defined as a systolic BP > or =Y180 mmHg with normal diastolic BP, the treatment goal is to reduce systolic BP to <160 mmHg. The evidence from most trials suggests that there are only minimal differences between the various antihypertensive drugs, and that almost all agents are capable of successfully reducing adverse clinical events. Nevertheless, there is evidence that certain drugs are more useful in preventing damage to a specific organ system; and therefore, the selection of the therapy should be guided by the presence of concomitant disease and the protection of the organ system that is most at risk. Beta-blockers and calcium channel blockers are effective antianginals; diuretics, angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are useful for heart failure; ACE inhibitors and angiotensin receptor blockers are especially effective in preserving renal function. Adequate BP control, irrespective of the type of antihypertensive drugs used, should replace the academic debate on what is the best antihypertensive agent.
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PMID:[Antihypertensive drugs in diabetic's hypertension]. 1663 91

IgA nephropathy (IgAN) is an important cause of progressive kidney disease with 25-30% of patients developing end-stage renal disease within 20 years of diagnosis. There is still no treatment to modify mesangial IgA deposition and available treatments are those extrapolated from the management of other patterns of chronic glomerulonephritis. There remains no consensus on the use of immunosuppressive agents for treatment of progressive IgAN and this is compounded by the relative lack in IgAN of randomized controlled trials relevant to current clinical practice. Patients with recurrent macroscopic hematuria or isolated microscopic hematuria and proteinuria <1 g/24 h require no specific treatment. Those with nephrotic syndrome and minimal change on renal biopsy should be managed as for minimal change nephropathy. There is no evidence to support the use of corticosteroids for nephrotic IgAN outside this group of patients. Patients presenting with acute renal failure require evaluation to distinguish acute tubular necrosis, which requires supportive therapy only, from crescentic IgAN, for which treatment with cyclophosphamide and corticosteroids in a regimen similar to that for renal small vessel vasculitis is indicated in the absence of significant chronic histologic injury. Patients at greatest risk of progressive renal impairment are those with hypertension, proteinuria >1 g/24 h, and reduced glomerular filtration rate at diagnosis. All such patients should be treated to a blood pressure of 125/75 mm Hg with dual blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibition and angiotensin receptor blockade. At present, there is insufficient evidence for the additional use of immunosuppressive agents, antiplatelet agents, or anticoagulants.
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PMID:Treatment of IgA nephropathy. 1705 Dec 61

The objective of the present study was to retrospectively examine whether the addition of minoxidil to patients who were already treated with maximum doses of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers but who had not achieved target blood pressures, has any detrimental effect on proteinuria or renal function or whether its effect on blood pressure prove salutary. The clinical records of the patients seen at the Hypertension, Nephrology, Dialysis and Transplantation Clinic from June 1982 through May 2005 were reviewed to identify 54 patients (78% men, 82% African-American) who had taken minoxidil (with and without angiotensin inhibition and blockade) and who had documented 24-hour urines for creatinine clearance and quantification of proteinuria before the initiation of minoxidil and after the blood pressure had stabilized on its final dose. The study was done at the Hypertension, Nephrology, Dialysis and Transplantation Clinic, the regional referral center for renal problems in eastern Alabama, USA. Minoxidil, whether alone or in combination with maximum doses of ACEIs and ARBs, was very successful in reduction of mean arterial pressure, but there was a tendency towards an increase in proteinuria. When minoxidil was given alone, patients demonstrated a trend towards reduction of proteinuria associated with blood pressure reduction; however, when minoxidil was added after the maximal doses of ACEIs and ARBs had been reached there was a significant increase in proteinuria (p = 0.017) on paired comparison in the same patients whose proteinuria had already demonstrated a significant decrease (p = 0.02) on the ACEI and ARB alone despite further significant reduction of blood pressure with the minoxidil (p = 0.003). Renal function deterioration to end stage renal disease correlated with increase in proteinuria (p = 0.03). We conclude that minoxidil was very effective in lowering systemic blood pressure but when given to patients already on maximum doses of ACEI and ARBs, there was an increase in proteinuria which could be interpreted as a detrimental effect having in mind that the blood pressure was significantly lowered.
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PMID:Does the hyperfiltration of minoxidil result in increased proteinuria and loss of renoprotection conferred by angiotensin inhibition? 1664 3

Declining kidney function predicts increasing cardiovascular risk in people with hypertension. Microalbuminuria is a marker for cardiovascular risk and declining kidney function. Agents that block the renin-angiotensin-aldosterone system (RAAS), notably angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), reduce proteinuria and microalbuminuria, lower blood pressure and slow the progression of proteinuric kidney disease. Evidence is accumulating that the combination of an ACE inhibitor and an ARB is the optimal means of RAAS blockade in this setting, slowing the progression of nephropathy independently of blood pressure lowering to a greater degree than can be achieved using maximum approved doses of either agent alone. However, the emerging therapeutic potential of ACE inhibitor/ARB combination therapy in hypertensive kidney disease requires further characterization. The Irbesartan in the Management of PROteinuric patients at high risk for Vascular Events trial aims to determine definitively whether the combination therapy of an ARB, irbesartan and an ACE inhibitor, ramipril, is more effective than ramipril alone in reducing the urinary albumin excretion rate in patients at high cardiovascular risk with hypertension and proteinuria or microalbuminuria.
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PMID:Rationale and design of a study to evaluate management of proteinuria in patients at high risk for vascular events: the IMPROVE trial. 1671 Feb 87

Blockade of the renin-angiotensin system with either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) was shown to decrease urinary protein excretion and slow the progression of both diabetic and nondiabetic proteinuric renal disease. The safety and efficacy of combined ACE-inhibitor and ARB therapy is not well established. We conducted a systematic review and meta-analysis of randomized trials evaluating the combination of an ACE inhibitor and an ARB in patients with chronic proteinuric renal disease. Twenty-one randomized controlled studies (n = 654 patients) were identified using MEDLINE, EMBASE, and Cochrane Central databases. Five trials had a parallel-group design and 16 trials used a crossover design. Combination therapy with an ACE inhibitor and an ARB resulted in a small, but significant, increase in serum potassium levels (weighted mean difference, 0.11 mEq/L [0.11 mmol/L]; 95% confidence interval [CI], 0.05 to 0.17) and a nonsignificant decrease in glomerular filtration rate (weighted mean difference, 1.4 mL/min [0.02 mL/s]; 95% CI, -2.6 to 0.2). Addition of an ARB resulted in a further decrease in proteinuria (weighted mean difference, 440 mg/d; 95% CI, 289 to 591) compared with an ACE inhibitor alone. This effect was observed in patients with diabetic (210 mg/d; 95% CI, 84 to 336) and nondiabetic (582 mg/d; 95% CI, 371 to 793) renal disease. In conclusion, the combination of ACE-inhibitor and ARB therapy in patients with chronic proteinuric renal disease is safe, without clinically meaningful changes in serum potassium levels or glomerular filtration rates. Combination therapy also was associated with a significant decrease in proteinuria, at least in the short term. Additional trials with longer follow-up are needed to determine whether the decrease in proteinuria will result in significant preservation of renal function.
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PMID:Combination therapy with an angiotensin receptor blocker and an ACE inhibitor in proteinuric renal disease: a systematic review of the efficacy and safety data. 1733 13

Angiotensin-II (Ang-II) type 1 (AT(1)) receptor blockers may delay the progression of chronic allograft nephropathy (CAN). However, neither the optimal time for initiating AT(1) receptor blockade in order to delay CAN potentially nor the role of Ang-II type 2 (AT(2)) receptors under AT(1) receptor blockade is known. Both AT receptors can regulate p53 expression and apoptosis. We investigated what time of initiation with AT(1) blockers most effectively delayed CAN as well as the role of the AT(2) receptor, and how angiotensin receptor blockade affected apoptosis and its regulating factors in this context in a rat model. Kidneys of Fisher (F344) rats were transplanted into Lewis rats. Animals were treated with AT(1) (candesartan) and/or AT(2) (PD123319) receptor antagonists, a calcium channel blocker, or vehicle (treatment periods: day -7 before to week 24 after transplantation (long term), week 12 to week 24 (late), day -7 to day +5 (early)) and observed the animals for 24 weeks. Reduction of proteinuria, grade of CAN, and number of apoptotic cells was most pronounced in animals receiving long-term AT(1) receptor blockade. A combined AT(1)/AT(2) blocker treatment reduced CAN similarly to AT(1) blocker treatment alone. The number of apoptotic cells and the level of p53 mRNA were significantly lower in long-term AT(1) blocker-treated animals. In summary, AT(1) receptor blockade delayed the progression of CAN, particularly in animals treated long term. Reduction of apoptosis could be related to these beneficial effects. The AT(2) receptor does not appear to play an important role in CAN.
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PMID:Angiotensin type 1 and type 2 receptor blockade in chronic allograft nephropathy. 1685 18

Angiotensin (Ang) II plays important roles in the development of hypertension and cardiovascular and renal injury. Pharmaceutical approaches to block its activity led to the development of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Numerous trials have documented their efficacy in controlling blood pressure, minimising left ventricular remodelling, preventing progression to heart failure, ameliorating proteinuria and retarding renal disease progression. Although they are considered safe in general, there remain concerns about the potential for adverse events in certain target populations. Recently, several novel, low molecular weight renin inhibitors without the extended peptide-like backbone of previous renin inhibitors were developed with favourable pharmacokinetic properties. They have been shown to successfully reduce Ang II levels in normal volunteers and to lower blood pressure in patients with mild-to-moderate hypertension. In this review, the authors summarise current knowledge about these renin inhibitors.
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PMID:Potential side effects of renin inhibitors--mechanisms based on comparison with other renin-angiotensin blockers. 1690 53

Intrarenally synthesized angiotensin II (Ang II) may be involved in the progression of glomerulonephritis, leading to irreversible glomerulosclerosis. There is increasing evidence that systemic angiotensin receptor blocker (ARB) treatment has beneficial effect on the prognosis of progressive glomerulonephritis and diabetic nephropathy. However, the cellular and molecular mechanisms behind this therapeutic effect of ARB remain unclear. In this study, we used a novel strategy of local ARB delivery via type-1 collagen sponge, to treat progressive glomerulonephritis that would result in irreversible glomerulosclerosis in our previously established rat model. At days 9 and 14 after disease induction, mild proteinuria, 20.7+/-4.7 and 10+/-1.3 mg/day, was found. Local ARB treatment reduced proteinuria significantly to 3.19+/-3.2 and 5.25+/-0.95 mg/day (P < 0.01), respectively. Scoring of glomerular matrix expansion and sclerotic index revealed that local ARB treatment significantly ameliorated glomerular pathology. Ang II type 1 receptor mRNA expression was remarkably enhanced in the Ang II group and ARB treatment reversed this effect at 14 days. Local delivery of ARB significantly improved glomerular blood flow levels, compared to the untreated disease control group, from 710+/-18.25 to 859.44+/-22.86 microm/s, respectively. Local delivery of ARB into the kidney affected local RAS and thus improved the renal injury and function in the potentially progressive glomerulosclerosis of rat model.
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PMID:Local delivery of angiotensin receptor blocker into the kidney ameliorates progression of experimental glomerulonephritis. 1698 12

Recent studies indicate that adding the mineralocorticoid receptor antagonist spironolactone (SP) to angiotensin converting enzyme inhibitors (ACEI) or ACEI and angiotensin receptor blocker (ARB), which is known as a triple blockade, enhances the more beneficial effects on urinary protein excretion of patients with chronic kidney diseases. In this study, we explored the effects of SP on urinary protein excretion in patients with Alport syndrome featuring persistent proteinuria in spite of the long-term use of ACEI (lisinopril) or both ACEI and ARB (candesartan). Five patients with Alport syndrome were enrolled and SP treatment (25 mg/day) was started. At the start of SP administration, all patients showed good renal function and none of them suffered from hypertension. We decided to assess the effect of SP by determining the morning urinary protein/creatinine ratio (U-P/C) and estimated glomerular filtration rate (EGFR). After SP treatment was started, U-P/C was significantly reduced at 3, 6, 12 and 18 months, while EGFR did not change. The drop in systolic and diastolic blood pressure was statistically significant and serum potassium level was slightly elevated. None of the patients showed signs of severe hyperkalemia (>5.0 mEq/l). These results suggest that aldosterone receptor blockade combined with ACEI and ARB therapy offers a valuable adjuvant treatment for the reduction of proteinuria in patients with Alport syndrome as in those with other chronic kidney diseases. SP can thus be expected to constitute a good renoprotective agent for Alport syndrome. These preliminary data indicate that large-scale trials of this therapy should be done.
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PMID:The effect of aldosterone blockade in patients with Alport syndrome. 1703 34

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