Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0730345 (microalbuminuria)
 4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eplerenone is a new aldosterone receptor antagonist that will be used in the treatment of hypertension. Like spironolactone, it is a compound that can be associated with the development of hyperkalemia. Therefore, the same prescription considerations that are applied to spironolactone should be directed to its use. Unfortunately, the label for eplerenone will place more stringent restrictions on its use than is the case for spironolactone. The basis for the multiple contraindications to the use of eplerenone is primarily that of concern for the development of hyperkalemia. This may occur with eplerenone, as has been the case with spironolactone. The presumption in the prescribing information that certain patient subsets, such as diabetics with microalbuminuria and/or patients with mild renal failure, would be highly prone to developing clinically relevant hyperkalemia with eplerenone is not, however, grounded in fact. The favorable experience with spironolactone is important. It should provide us with the landmarks for advancing knowledge on the role of newer aldosterone receptor antagonists in disease state management and one would think, help in establishing criteria for the safe use of new compounds. New compounds in a drug class typically provide advantages over earlier entries into a drug class but not if regressive labeling has occurred. Time and additional clinical experience with eplerenone will establish its safety profile and determine if the original label for this compound was correct.
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PMID:Eplerenone: a new aldosterone receptor antagonist--are the FDAs restrictions appropriate? 1246 13

Outcome studies in diabetic nephropathy have focused on strategies to prevent progression of diabetic nephropathy, the leading cause of ESRD in the United States. Once diabetics develop overt nephropathy, prognosis is poor. Risk factors for diabetic nephropathy are discussed, and include hyperglycemia, hypertension, angiotensin II, proteinuria, dyslipidemia, smoking, and anemia. Major outcomes as well as outcome studies in diabetic nephropathy for patients with microalbuminuria and macroalbuminuria are reviewed. Furthermore, the role of therapy with angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, and mineralocorticoid receptor antagonists as well as selected combination therapy are discussed. Recommendations for therapy with ace inhibitors and angiotensin II receptor blockers are made based on this evidence.
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PMID:Outcome studies in diabetic nephropathy. 1283 94

Eplerenone is a specific aldosterone receptor antagonist that has been shown to have antihypertensive efficacy and to reduce end-organ manifestations in experimental animal models. Studies in humans have confirmed the blood pressure-lowering efficacy of this agent, as well as providing evidence of benefit in congestive heart failure. The side-effect profile indicates that the specificity of eplerenone for the mineralocorticoid receptor is responsible for the lower incidence of sex hormone- related side-effects than have been seen with other mineralocorticoid receptor blockers. Hyperkalemia is most frequently observed with eplerenone among patients with severe impairment of renal function and in diabetics with microalbuminuria, especially in combination with angiotensin-converting enzyme inhibitors. This agent appears to be a promising and effective new addition for the treatment of hypertension and heart failure with few of the side-effects that have plagued earlier drugs of this class.
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PMID:Eplerenone: a new selective aldosterone receptor antagonist. 1534 28

Albuminuria is recognized in all hypertension guideline statements as a cardiovascular risk factor and indicator of kidney disease. Recent data also demonstrate a strong association between the presence of microalbuminuria and elevations in C-reactive protein. Thus, the increased membrane permeability that generates microalbuminuria may be secondary to an inflammatory process. Progression from microalbuminuria (>30 and < or =300 mg albumin/g creatinine) to macroalbuminuria (>300 mg albumin/g creatinine) indicates a worsening of vascular disease and the presence of kidney disease. Recent outcome trials of kidney disease progression have demonstrated the best results among those with reductions in albuminuria in concert with blood pressure (BP) reduction. Thus, use antihypertensive agents that not only lower BP but also lower or normalize albuminuria levels. All recent guideline statements support the use of agents that block the renin-angiotensin-aldosterone system as part of a regimen to achieve the BP goal. Further lowering of albuminuria may be achieved by adding either a nondihydropyridine calcium antagonist such as verapamil or diltiazem, or aldosterone receptor blockers. Use of an angiotensin receptor blocker added to an angiotensin-converting enzyme inhibitor or vice versa can further lower albuminuria by an additional 30%-40%, which is not true of the additional lowering of BP.
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PMID:Implications of albuminuria on kidney disease progression. 1553 7

The incidence of end-stage renal disease (ESRD) is rising worldwide, accompanied by corresponding increases in the risk of morbidity and mortality. Underlying this trend are increasing rates of hypertension and diabetes mellitus, the two most common causes of ESRD. In addition to the adverse haemodynamic effects of hypertension on the kidney, elevated blood pressure (BP) can activate components of the renin-angiotensin-aldosterone system (RAAS), which, in turn, activate mediators of inflammation, oxidative stress, cell growth, and matrix accumulation. Lowering BP reduces the risk of cardiovascular events and renal damage. Accumulating evidence from clinical and laboratory studies suggests that interrupting the RAAS with therapies such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and aldosterone receptor blockers can interfere with the mechanisms that promote diabetic and non-diabetic renal damage. Moreover, clinical trials of RAAS blockade have demonstrated reductions in microalbuminuria, a predictor of increased cardiorenal risk and overt nephropathy in patients with and without diabetes and/or hypertension. In this way, agents that block the RAAS should be considered the drugs of first choice as they provide enhanced renoprotection compared with other classes of antihypertensive agents such as calcium channel blockers and beta-blockers.
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PMID:Evidence for renoprotection by blockade of the renin-angiotensin-aldosterone system in hypertension and diabetes. 1645 96

Increasing evidence suggests that circulating aldosterone per se contributes directly to renal and cardiovascular diseases. We sought to evaluate the effects of a three-month treatment with 25 mg spironolactone, an aldosterone receptor antagonist, on nephron function in 20 type II diabetic patients with persistent microalbuminuria, despite at least six months' use of an ACEi or ARB (combination group), and in eleven type II diabetic patients with persistent microalbuminuria who have never used an ACEi or an ARB (spironolactone group). In the combination group, urinary protein excretion (UPE, p = 0.015), urinary albumin excretion (UAE, p = 0.010), and the urinary albumin to creatinine ratio (ACR, p = 0.007) decreased, and serum potassium (sK(+), p = 0.004) was significantly elevated. ACR (p = 0.016) decreased significantly in the spironolactone group. In 31 patients given spironolactone (all patients group), UPE (p = 0.019), UAE (p = 0.002), and ACR (p = 0.011) decreased, and serum creatinine (sCr, p = 0.025) and sK(+) (p = 0.002) were significantly elevated. Changes in albuminuria showed a positive correlation with changes in GFR (p = 0.002) and a negative correlation with changes in sCr (p = 0.007), and changes in ACR showed a negative correlation with changes in sCr (p = 0.004) in all patient groups. In our study, we observed that spironolactone, both alone and in combination with ACEi/ARB treatment, was well tolerated, and that it slowed down the progression of diabetic nephropathy with a marked antialbuminuric effect. Our results showed that the antialbuminuric effect developed by the decrease of intraglomerular pressure, particularly in patients with persistent microalbuminuria despite long-term ACEi/ARB treatment; adding aldosterone blockers to treatment was beneficial.
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PMID:The effects of spironolactone on nephron function in patients with diabetic nephropathy. 1901 50

Primary aldosteronism is the most common cause of secondary hypertension, accounting for about 10% of all forms of high blood pressure. Life-time pharmacological therapy is the treatment of choice for primary aldosteronism due to idiopathic adrenal hyperplasia (IHA), while adrenalectomy is effective in curing most patients with an aldosterone producing adenoma (APA). Far from being a benign form of hypertension, primary aldosteronism is characterized by the development of cardiovascular renal and metabolic complications, including left ventricular hypertrophy, myocardial infarction, atrial fibrillation and stroke, microalbuminuria, renal cysts as well as metabolic syndrome, glucose impairment and diabetes mellitus. We review recent clinical experience with the above mentioned complications and long-term outcomes of blood pressure normalization and cardiac, renal and gluco-metabolic complications in patients with primary aldosteronism, after medical treatment with mineralocorticoid receptor antagonists and surgical treatment. We conclude that removal of adrenal adenoma results in normalization of the renin-angiotensin-aldosterone system (RAAS) and of kalaemia and improvement of blood pressure levels in all patients. Complete resolution of hypertension is achieved in nearly half of treated patients. Moreover, unilateral adrenalectomy is the best treatment to have the regression of cardiovascular, renal and metabolic complications in patients with APA. On the other hand, targeted medical treatment with aldosterone antagonists improves blood pressure control and appears able to prevent the progression of cardiac and metabolic complications in patients with IHA.
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PMID:Management of primary aldosteronism: its complications and their outcomes after treatment. 1935 5

Obese persons with metabolic syndrome often have associated with salt-sensitive hypertension, microalbuminuria, and cardiac dysfunction, and the plasma aldosterone level in one-third of metabolic syndrome patients is clearly elevated. Hyperaldosteronism, which may be caused at least partially by certain adipocyte-derived factors, contributes to the development of proteinuria in obese hypertensive rats, and salt loading aggravates the proteinuria and induces cardiac diastolic dysfunction because of inadequate suppression of plasma aldosterone level. However, mineralocorticoid receptor (MR) antagonists prevent salt-induced renal and cardiac damage, suggesting that aldosterone excess and a high-salt diet exert an unfavorable synergistic action on the kidney and heart. In Dahl salt-sensitive rats, however, despite appropriate suppression of plasma aldosterone with a high-salt diet, salt loading paradoxically activated renal MR signaling, and the renal injury was markedly prevented by MR antagonists. Accordingly, we discovered an alternative pathway of MR activation in which Rac1, a small GTP-binding protein, activates MRs. Salt loading activates renal Rac1 in Dahl salt-sensitive rats, and Rac1 in turn induces MR activation, which results in renal injury, and the renal injury has been found to be prevented by Rac1 inhibitors. Moreover, several metabolic syndrome-related factors induce Rac1 activation, and one of them, hyperglycemia, activates MRs via Rac1 activation. Consistent with this, Rac1 inhibitors attenuated the proteinuria and renal injury in obese hypertensive animals. Thus, both salt and obesity activate Rac1 and cause MR activation. Abnormal activation of the aldosterone/MR pathway plays a key role in the development of salt-sensitive hypertension and renal injury in metabolic syndrome.
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PMID:Mineralocorticoid receptors, salt-sensitive hypertension, and metabolic syndrome. 2017 94

Women with a history of hypertension in pregnancy are at increased risk of microalbuminuria later in life. Microalbuminuria is a marker of kidney dysfunction frequently related to an inflammatory event. Pregnancy is a dynamic process characterized by immune tolerance, angiogenesis, and hormonal regulation. Menstruation and pregnancy are associated with a physiological inflammation, which is altered in preeclampsia and probably in other hypertensive situations of pregnancy. An imbalance between pro-oxidant factors and the ability to scavenge these factors produces oxidative stress, which has been evaluated in many cells, but leukocytes are the main source of inflammatory cytokines and experimental and clinical evidence support a possible role of aldosterone as a mediator of placental and renal damage mediated by growth factors, reactive oxygen species, and cytokines. Angiotensin-converting enzyme inhibitors and aldosterone receptor blockers are frequently effective in reducing the risk of progression of cardiovascular and renal disease.
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PMID:Microalbuminuria and hypertension in pregnancy: role of aldosterone and inflammation. 2403 53

Primary aldosteronism (PA) has been associated with increased target organ damage (TOD), most likely through mineralocorticoid receptor-dependent endothelial dysfunction, in comparison with essential hypertension (EH). The aim of this study was to evaluate the level of biomarkers of endothelial dysfunction in PA and the relationship with left ventricular hypertrophy (LVH) and microalbuminuria (MAU). A total of 50 PA patients and 51 patients with EH individually matched for age, sex, blood pressure and duration of hypertension participated in this study. Biomarkers of endothelial dysfunction, including von Willebrand factor (vWF), intercellular adhesion molecule 1 (ICAM-1) and oxidized low-density lipoprotein (ox-LDL), were measured. Plasma aldosterone concentration (PAC), MAU and echocardiography were also evaluated. In PA patients, vWF, ICAM-1, ox-LDL, LVH and MAU were all significantly higher than in EH patients (all P<0.05). Furthermore, LVH was positively correlated with PAC (P=0.002), vWF (P=0.013) and ox-LDL (P=0.020). MAU was positively correlated with PAC (P<0.001), vWF (P=0.013) and ICAM-1 (P=0.001). Multiple regression analysis indicated that vWF, ICAM-1 and PAC independently predicted MAU (all P<0.05). Likewise, PAC, vWF and ox-LDL were significant predictors of LVH (all P<0.05). Taken together, our results suggest that endothelial dysfunction may contribute to TOD in PA patients.
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PMID:Endothelial dysfunction in patients with primary aldosteronism: a biomarker of target organ damage. 2455 36


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