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 metabolic syndrome is a main cause for cardiovascular disease and for the accelerating epidemic of chronic renal failure. Previous studies show that 2-hydroxyestradiol (2-HE), an estradiol metabolite with little estrogenic activity, decreases obesity and arterial blood pressure and attenuates the development of renal disease in young, obese, diabetic ZSF1 rats. In humans, however, diabetic renal disease is more frequent and severe in older patients. In vivo, 2-HE is readily converted to 2-methoxyestradiol (2-ME), an estradiol metabolite with no estrogenic activity. Accordingly, one purpose of this study was to determine whether 2-ME would provide benefit in aged rats with a very severe form of diabetic renal disease. Another objective was to determine whether synthetic analogs of estradiol metabolites might be beneficial in diabetic renal disease. To achieve these objectives we examined the effects of 2-ME and its analog 2-ethoxyestradiol (2-EE) in aged (35-week-old), obese ZSF1 rats. Animals were treated for 9 weeks with vehicle (PEG-400, 0.5 microL per hour), 2-ME or 2-EE (18 microg/kg per hour). Metabolic and renal function were measured at weeks 0, 3, 6, and 9, and renal hemodynamics and excretory function were assessed at week 9. Aged ZSF1 rats had elevated levels of glycosylated hemoglobin; increased renal cortical expression of proliferating cell nuclear antigen (PCNA), nuclear factor kappa B (NF-kappaB), and vascular endothelial growth factor (VEGF); glycosuria, hypertension; and proteinuria. 2-ME and 2-EE did not affect obesity or hypertension and had variable effects on glucose homeostasis, yet they attenuated proteinuria; increased renal blood flow and glomerular filtration; and reduced renal cortical expression of PCNA, NFkappaB, and VEGF. We conclude that 2ME and 2EE are strikingly renoprotective even in aged animals with severe diabetic renal disease. The present study warrants further investigation of 2-ME and analogs of estradiol metabolites for treatment of kidney disease associated with the metabolic syndrome.
J Cardiovasc Pharmacol 2007 Jan
PMID:2-Methoxyestradiol and 2-ethoxyestradiol retard the progression of renal disease in aged, obese, diabetic ZSF1 rats. 1726 64

Pregnancy is a metabolic and vascular 'stress test' for women and those who 'fail' are at increased risk of long-term cardiovascular complications. Specifically, women who develop preeclampsia (and/or other manifestations of placental dysfunction) are at increased risk of coronary heart disease, stroke and cardiovascular disease in general. The risk is highest among women who develop both maternal (e.g., hypertension and proteinuria) and fetal (e.g., intrauterine growth restriction) manifestations of abnormal placentation, especially with preterm delivery. Most women who develop a maternal placental syndrome return to a normal clinical state in the weeks following pregnancy and their absolute risk of cardiovascular disease in the short term is very low. However, perhaps having a placentally complicated pregnancy affords women the opportunity to personalize risk and take action. Action is needed. The fact that we, as a population, are getting heavier and more sedentary is an urgent public health issue. The American Heart Association recommends that all women (even those at low cardiovascular risk) pursue dietary and lifestyle changes, in addition to smoking cessation. Engaging women of child-bearing age who may be motivated by a complicated pregnancy would be very valuable, from a public health perspective, given the prevalence and importance of cardiovascular disease in women, and the central role of the woman as caregiver to children, spouses and other family members.
Expert Rev Cardiovasc Ther 2007 Mar
PMID:Preeclampsia and future cardiovascular risk. 1733 72

Insulin resistance (IR) is commonly associated with other cardiovascular risk factors and is considered an independent risk factor for cardiovascular disease and events. The hyperinsulinemic euglycemic clamp technique is considered the gold standard for evaluating IR, but this technique is cumbersome and not easily applicable in large studies. Therefore, there are no long-term follow-up published studies on the relationship between IR determined by this technique and cardiovascular outcome. Thirteen years ago we performed a hyperinsulinemic euglycemic clamp in 31 hypertensive patients, 16 of whom manifested IR and 15 had normal insulin sensitivity. Thirteen years later we were able to re-evaluate or obtain medical records for all these patients. Over these years, 11 of the 16 insulin resistant patients developed cardiovascular disease and events, including two cardiovascular deaths, two myocardial infarctions, one angina pectoris, one peripheral vascular disease, and five carotid plaques or stenosis. Moreover, two patients developed new onset diabetes, one proteinuria and two impaired kidney function. Among insulin-sensitive patients, one developed peripheral vascular disease, one new onset diabetes and one proteinuria. In conclusion, this is the first longitudinal study of the relationship between insulin resistance, measured by the hyperinsulinemic euglycemic clamp and cardiovascular disease and events in a small cohort of patients with essential hypertension. The data suggest that hypertensive patients with IR are at greater risk of developing cardiovascular disease and events than hypertensive patients with normal insulin sensitivity.
Nutr Metab Cardiovasc Dis 2008 May
PMID:Increased cardiovascular events in hypertensive patients with insulin resistance: a 13-year follow-up. 1736 7

Concerns have been raised because of observations of proteinuria associated with rosuvastatin treatment. In this open-label study, a potential dose-dependent effect was investigated of rosuvastatin on urinary protein excretion and renal function parameters in 90 hyperlipidemic patients randomly assigned to rosuvastatin 10 mg/day (n = 45) or 20 mg/day (n = 45). Urinary samples were collected from patients and 40 age- and gender-matched controls to determine electrolyte, uric acid, creatinine, and protein (total, albumin, IgG, and alpha1-microglobulin) levels at baseline and after 12 weeks. A dose-dependent increase in the excretion of alpha1-microglobulin (17.6% in rosuvastatin 10 vs 34.9% in rosuvastatin, 20 mg/day; P = .03 for the comparison between groups) was observed. A trend toward an increase in the estimated glomerular filtration rate was noted in only patients receiving 20 mg/day of rosuvastatin. These findings indicate that rosuvastatin treatment increases the urinary excretion of alpha1-microglobulin urinary excretion in a dose-dependent manner without adversely affecting renal function.
J Cardiovasc Pharmacol Ther 2007 Dec
PMID:Dose-dependent effect of rosuvastatin treatment on urinary protein excretion. 1817 23

The purpose of this study was to describe the indications for and technique of transjugular renal biopsy (TJRB) and evaluate the efficacy and complications of this method. We performed a retrospective review of 59 patients who underwent TJRB using the Quick-core needle biopsy system (Cook, Letchworth, UK) over a 4-year period. The indications for obtaining renal biopsy included acute renal failure, chronic renal failure, nephrotic syndrome, and proteinuria with or without other associated disease. Indications for the transjugular approach included coagulopathy, biopsy of a solitary kidney or essentially single functioning kidney, simultaneous renal and hepatic biopsy, morbid obesity, and failed percutaneous biopsy. All but four cases were performed via the right internal jugular vein. The right, left, or both renal veins were cannulated in 41, 14, and 4 cases, respectively. Combined liver and renal biopsies were obtained in seven cases. Diagnostic biopsy specimens were obtained in 56 of 59 patients (95%). The number and size of tissue cores ranged from 1 to 9 mm and from 1 to 20 mm, respectively. The mean numbers of glomeruli per procedure on light microscopy and electron microscopy were 10.3 and 2.6, respectively. Specimens for immunohistology were acquired in 49 cases, of which 40 were adequate. Of the 56 successful TJRB procedures, 34 (61%) were associated with isolated capsular perforation (19), contained subcapsular leak (10), isolated collecting system puncture (1), and concurrent collecting system and capsular perforation (4). There was a significant increase in capsular perforation with six or more needle passes, although no significant correlation was seen between number of needle passes and complication. Six patients had minor complications defined as hematuria or loin pain. Seven patients developed major complications, of whom five received blood transfusion alone. Two required intervention: in one an arteriocalyceal fistula was embolized and the patient was temporarily dialyzed; the remaining patient required ureteric stenting. In conclusion, TJRB provides an adequate yield for diagnosis. Complication rates are relatively high, but patients are also at high risk from the conventional percutaneous approach. Patient selection and optimization are critical to avoid major complications.
Cardiovasc Intervent Radiol
PMID:Transjugular renal biopsy: our experience and technical considerations. 1826 29

Angiotensin II type 1 (AT(1)) receptor antagonists (blockers) [ARBs] are highly selective for the AT(1) receptor and block the diverse effects of angiotensin II. When high BP is not controlled by low-dose ARB monotherapy, physicians need to employ another strategy, either high-dose ARB monotherapy or combination therapy with calcium channel antagonists (blockers) [CCBs], diuretics, or other agents. High-dose ARB monotherapy is more effective for decreasing proteinuria than low-dose ARB monotherapy or CCBs. Although the ARB valsartan has been shown to prevent coronary restenosis in a clinical study (Val-PREST [Valsartan for prevention of restenosis after stenting of type B2/C lesions]), it is still unclear whether ARBs help to prevent restenosis. The results reported by Peters in this issue highlight the relative efficacies of low- (80 mg/day) and high-dose valsartan (160-320 mg/day) for the prevention of in-stent restenosis after the implantation of bare-metal stents, and suggest that high-dose valsartan can reduce the in-stent restenosis rate, target lesion revascularization and target vessel revascularization rates, late lumen loss, and major adverse cardiac events rate more effectively than low-dose valsartan. A better understanding of the differences in the efficacies of high- and low-dose ARBs could be useful in the treatment of patients with cardiovascular disease and may resolve the issue of whether ARBs prevent coronary restenosis. Clinical benefits may be induced by complete blockade of the renin-angiotensin system using high-dose ARB monotherapy. Therefore, physicians need to select a strategy carefully; i.e. either high-dose ARB monotherapy or combination therapy.
Am J Cardiovasc Drugs 2008
PMID:Which strategy is more effective for the treatment of cardiovascular disease: high-dose angiotensin II type 1 receptor antagonist monotherapy or combination therapy? 1842 91

Renal pathophysiology is elicited by activation of angiotensin II type 1 (AT(1)) receptors at all stages of renovascular disease. Angiotensin receptor blockers (ARBs) that specifically block the AT(1) receptor offer the potential to prevent or delay progression to end-stage renal disease independently of reductions in blood pressure. Proteinuria--an early and sensitive marker for progressive renal dysfunction--is reduced by ARB use in patients with type 2 diabetic nephropathy and microalbuminuria or macroalbuminuria. Retrospective analysis of data available from early trials has confirmed this finding and has shown that albuminuria reduction is associated with lessening of cardiovascular risk. The ARB telmisartan is equivalent to enalapril in preventing glomerular filtration rate decline, and equivalent to valsartan in reducing proteinuria. Telmisartan is more effective than conventional therapy in lowering the risk of transition to overt nephropathy in hypertensive and normotensive patients. An additive effect has been seen in smaller studies when telmisartan has been added to lisinopril therapy, and high-dose telmisartan reduces albuminuria better than low-dose telmisartan. Similar data were obtained with other ARBs such as candesartan, losartan, valsartan, or irbesartan. These data support the proposition that blockade of the renin-angiotensin system beyond that required for maximum blood pressure reduction provides optimum renal protection.
Nat Clin Pract Cardiovasc Med 2008 Jul
PMID:Reduction of proteinuria with angiotensin receptor blockers. 1858 Aug 65

The metabolic syndrome, also known as the cardiometabolic syndrome (CMS), is a state of metabolic and vascular dysregulation that is associated with activation of the renin-angiotensin-aldosterone system (RAAS). Clinical components of the CMS include central or visceral obesity, hypertension (HTN), dyslipidemia, insulin resistance/hyperinsulinemia, and microalbuminuria that collectively convey increases in oxidative stress, inflammation, and subsequent endothelial dysfunction. The cardio-renal inflammation and oxidative stress enhanced in the CMS increases the risk for cardiovascular disease (CVD) and renal disease end-points such as stroke, congestive heart failure, and chronic kidney disease (CKD). The development of proteinuria is known to herald progressive kidney disease (e.g. CKD) and both are now well accepted as CVD risk factors. Evidence suggests a role for visceral obesity, insulin resistance/hyperinsulinemia, HTN, and other components of the CMS lead to an increased risk for proteinuria and progressive loss of renal function. Intervention with agents that block the RAAS (e.g. ACE inhibitors and Angiotensin type 1 receptor blockers) have been shown to reduce proteinuria, CKD progression, and CVD events. Herein, we will examine the relationship between RAAS intervention and reductions in CKD and CVD events.
Ther Adv Cardiovasc Dis 2007 Oct
PMID:Renin-angiotensin-aldosterone system intervention in the cardiometabolic syndrome and cardio-renal protection. 1912 93

Clinical Pharmacology is commonly accepted to be a bridging discipline between basic science observations and clinical practice. Today, it should be a major task of the clinical pharmacologist in academia to provide support in the interpretation of preclinical and clinical study data, to develop evidence-based treatment guidelines and to serve as drug expert supporting all disciplines of clinical medicine with specific pharmacological and therapeutic knowledge. The results of the ONTARGET-trial confront both researchers and clinicians with the unexpected truth that AT(1)-receptor-blockade with an angiotensin-receptor-blocker (ARB) does not seem to have superior therapeutic benefit compared with an ACE-inhibitor (ACE-I) at reducing fatal and nonfatal cardiovascular events. The combination of the two drugs was associated with more adverse events without an increase in benefit. Therefore, the crucial question 'ACE-I, ARB, or both?' requires a new and critical appraisal depending on the medical indication for which these renin-angiotensin-system (RAS)-inhibitors are used: In a population of high-risk patients suffering from cardiovascular disease or diabetes mellitus, the evidence to favor an ARB over an ACE-I is still limited after ONTARGET and because of the higher costs for ARBs one can rather support the old therapeutic advice that ARBs are equally effective as ACE-Is and therefore therapeutic alternatives for patients with ACE-I intolerance. With respect to a very moderate additive BP-lowering effect of dual therapy with an ACE-I and an ARB seen in metaanalysis which was not even clearly attributable to dual RAS-inhibition and the increased adverse event rate in the combination treatment group of ONTARGET, this regimen seems not to be recommendable for the treatment of hypertension. Dual-RAS-blockade using an ACE-I-ARB-combination is an effective therapy to treat proteinuria and might be of therapeutic benefit especially in diabetic patients without concomitant diseases. There may be a therapeutic rationale to prefer ARBs over ACE-Is in well-selected patients with congestive heart failure (CHF) because a considerable amount of angiotensin II (Ang II) is produced independent of angiotensin-conversion-enzyme (ACE) in the failing heart and is therapeutically unaffected by ACE-I treatment. The results of the Val-HeFt and the CHARM-added-study revealed additive effects of an ARB on heart failure related morbidity and mortality when added to existing therapy with an ACE-I suggesting a role for ACE-I-ARB-combination treatment in well selected heart failure patients. Independent of the medical indication for its use, the concept of dual RAS-blockade with an ARB-ACE-I-combination should clinically be used with caution and a close monitoring of potassium levels and kidney function. Although the results of ONTARGET revealed equity of ramipril and telmisartan at reducing fatal and nonfatal cardiovascular events, we should not forget that pharmacologically not all ARBs are the same and the question if the study results of ONTARGET with telmisartan are transferable to the complete class of ARBs still merits further investigation.
Ther Adv Cardiovasc Dis 2008 Aug
PMID:ACE-inhibitor, AT1-receptor-antagonist, or both? A clinical pharmacologist's perspective after publication of the results of ONTARGET. 1912 24

It is estimated that 10% of pregnancies are affected by hypertension worldwide. Approximately one-half of all hypertensive pregnancy disorders are due to preeclampsia, a pregnancy-specific disorder, its distinctive feature being either sudden onset, or worsening of pre-existing proteinuria. It has become increasingly recognized that women with a history of preeclampsia are at increased risk for future cardiovascular disease (CVD), but the mechanisms of this increase in risk are unclear. One possible explanation is that these two conditions share several common metabolic abnormalities as risk factors, including obesity, insulin resistance, and lipid abnormalities that may lead to preeclampsia and CVD at different times of a woman's life. Recent studies have revealed that, similar to CVD, several mediators of endothelial cell dysfunction are up-regulated in preeclampsia. Free radical derived oxidative stress, various inflammatory markers, including neutrophil response, C-reactive protein, and leukocyte adhesion, may contribute to endothelial dysfunction in both preeclampsia and coronary atherosclerosis. Alternatively, preeclampsia itself may induce metabolic and vascular changes that may increase the overall future risk for CVD in affected women. Therefore, at present, it remains unclear whether preeclampsia is a formal risk factor for CVD, or identifies women at increased risk for CVD later in life. Pending large-scale studies aiming to examine the causality of this association, women with a history of preeclampsia should be counseled regarding their increased risks for hypertension and other cardiovascular sequelae later in life, followed closely and treated aggressively for modifiable CVD risk factors.
Ther Adv Cardiovasc Dis 2008 Aug
PMID:Preeclampsia and future cardiovascular risk: formal risk factor or failed stress test? 1912 25


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