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)

Considering the increasing incidence of diabetic nephropathy and its serious complications, the prevention of nephropathy evolution risk in diabetic patients is the subject of several recently initiated studies. In diabetic patients with advanced nephropathy, the lowering of proteinuria by renin angiotensin system blockers induces an evolution risk reduction, which can be further improved by increasing the dose of angiotensin II receptor antagonist (ARA II). Such a synergy can be also obtained with the association of an ARA II and an angiotensin converting enzyme (ACE) inhibitor, provided that the diuretic dose given to the patient is increased. In terms of cardiovascular risk, diabetic patients benefit from this type of treatment, as cardiovascular events increase with the level of proteinuria. In micro-albuminuria patients, sufficient doses of ARA II or ACE inhibitors are needed to avoid relapse after treatment discontinuation. In normo-albuminuria patients also, the treatment with a renin angiotensin system blocker significantly decreases the risk of development of microalbuminuria. Thus, the reduction of proteinuria or the prevention of its appearance with renin angiotensin system blockers is the main therapeutic strategy to prevent the evolution of nephropathy in diabetic patients.
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PMID:[Clinical studies on chronic diabetic nephropathy and recent data concerning prevention of risks of nephropathy and cardiovascular diseases]. 1737 Aug 50

To explore the effects of various antihypertensive regimes on microalbuminuria, an angiotensin II receptor blocker (ARB), valsartan, was substituted for or added to treatment with a calcium channel blocker (CCB). After a 6-month CCB baseline period, 28 Japanese hypertensive patients with incipient diabetic nephropathy (defined as a urinary albumin excretion [UAE] of 30-300 mg/g creatinine), were assigned to two groups according to their blood pressure (BP) levels: in patients with a BP of more than 130/85 mmHg (n=17), valsartan was added to the CCB (Group A), while in patients with a BP <130/85 mmHg, valsartan alone was given (Group B: n=11) for 12 months. UAE was determined before and at 3, 6 and 12 months after the initiation of ARB. Although the initial BP was significantly higher in Group A (150/83 mmHg) than Group B (127/77 mmHg), BP was decreased to 141/78 mmHg in Group A and slightly, but not significantly, increased to 130/82 mmHg in Group B. In both groups, UAE was significantly decreased after ARB treatment (to 89% of the basal value in Group A and to 40.5% of the basal value in Group B) and did not differ each other and the amount of decrease did not differ significantly between the two groups. These results suggest that combination therapy with an ARB and CCB is very effective in lowering BP and UAE in cases in which BP is not well controlled, while, even in patients with a sufficient BP control of <130/85 mmHg, the use of ARB singly resulted in a significant decrease in UAE without a further decrease in BP, implying that the ARB had a renoprotective action independent of changes in BP.
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PMID:Is renoprotection by angiotensin receptor blocker dependent on blood pressure?: the Saitama Medical School, Albuminuria Reduction in Diabetics with Valsartan (STAR) study. 1766 56

To reduce the burden of cardiovascular disease (CVD), management strategies are increasingly focusing on preventive measures following early detection of markers of atherosclerosis. This review focuses on microalbuminuria, which is gaining recognition as a simple marker of an atherogenic milieu. Prospective and epidemiologic studies have found that microalbuminuria is predictive, independently of traditional risk factors, of all-cause and cardiovascular mortality and CVD events within groups of patients with diabetes or hypertension, and in the general population. The pathophysiologic mechanism underlying the association between albumin excretion and CVD is not fully defined. One hypothesis is that microalbuminuria may be a marker of CVD risk because it reflects subclinical vascular damage in the kidneys and other vascular beds. It may also signify systemic endothelial dysfunction that predisposes to future cardiovascular events. Based on this theory, periodic screening for microalbuminuria could allow early identification of vascular disease and help stratify overall cardiovascular risk, especially in patients with risk factors such as hypertension or diabetes. A positive test for urinary albumin excretion could signify the need for an intensive multifactorial intervention strategy, including behavior modification and targeted pharmacotherapy, aimed at preventing further renal deterioration and improving the overall CVD risk factor profile. Data from intervention studies suggest that treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, statins, and/or strict glycemic control (in diabetics) offer significant reductions in cardiovascular and/or renal morbidity in patients with albuminuria. Use of this (old) marker may allow improved use of medications and strategies for secondary prevention.
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PMID:Microalbuminuria and cardiovascular disease. 1769 66

The subjects of the study were 29 men (mean age 37.7+/-9.3 years) suffering from abdominal obesity without carbohydrate exchange disturbances or signs of chronic renal diseases. The results of the study show that the surplus of leptin, typical of obese patients, leads to the development of intrarenal vascular endothelial dysfunction, which is manifested by microalbuminuria, the growth of endothelin-1 serum level, and endothelium-dependent vasodilatation impairment, leading to unfavorable changes in renal filtration. Administration of angiotensin II receptor blockers results in the elimination of microalbuminuria and the recovery of endothelium-dependent vasodilatation in obese patients.
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PMID:[Endothelial dysfunction and renal lesion in obesity]. 1778 69

Microalbuminuria is a strong, consistent and independent risk factor for cardiovascular and renal disease in patients with diabetes and/or hypertension and in the general population. Several randomized trials have shown the efficacy of inhibiting the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) to prevent cardiovascular events and the progression of kidney disease. These 2 classes of drugs are equally effective for renal outcomes in patients with diabetic nephropathy, but only ACEIs have been found to significantly impact the risk of all-cause mortality, predominantly cardiovascular, in patients with diabetic nephropathy. Studies on the cardiorenal efficacy of combined therapy with ACEIs and ARBs in individuals with microalbuminuria or macroalbuminuria and other cardiovascular risk factors have been inconclusive. The Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) study aims to address existing questions in this setting. This is a phase III, randomized, comparative, pragmatic trial with prospective randomized open blinded endpoint (PROBE) design. It will evaluate the comparative efficacy of combined therapy with ACEIs and ARBs versus monotherapy with either ACEIs or ARBs in improving cardiovascular and renal outcomes in microalbuminuric or macroalbuminuric individuals at cardiorenal risk. The study will enroll 2,100 patients, selected in a network of internal medicine, diabetology or nephrology outpatient clinics. Patients will be randomly allocated to ACEIs, ARBs or their combination. The study has been approved and funded by the Agenzia Italiana del Farmaco (A.I.F.A.) within the 2005 funding plan for independent research on drugs.
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PMID:Protocol of the Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) randomized trial. 1804 66

Proteomic methods have found broad applications in kidney disease research and more specifically in diabetic nephropathy (DN) research. Proteomic methods such as 2-dimensional gel electrophoresis have been used to gain insight into glomerular and tubular nephropathies including DN. At the protein level, differences in high-abundant proteins in DN have been shown to reflect primarily differentially posttranslationally modified plasma proteins. Higher-sensitivity proteomic methods (eg, liquid chromatography-mass spectrometry) have pushed the boundaries on the known urinary proteome to include more than 1,500 proteins. These same high-sensitivity methods have been applied toward profiling urinary peptides, which has resulted in methods to diagnostically screen urine to differentiate between type-2 diabetes mellitus and type-1 diabetes mellitus urine, normal versus microalbuminuria, or by angiotensin II receptor blocker treatment. Proteomic methods are being used to show response to insulin gene therapy in an animal model or alterations in the renal cortex mitochondrial proteome with the development of the diabetic phenotype. Proteomic methods continue to aid in the discovery of new mechanisms of diabetic pathology and understanding of the etiology of diabetic complications.
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PMID:Proteomics and diabetic nephropathy. 1806 45

Despite the huge amount of studies looking for candidate genes, the ACE gene remains the unique, well-characterized locus clearly associated with pathogenesis and progression of chronic kidney disease, and with response to treatment with drugs that directly interfere with the renin angiotensin system (RAS), such as angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA). The II genotype is protective against development and progression of type I and type II nephropathy and is associated with a slower progression of nondiabetic proteinuric kidney disease. ACE inhibitors are particularly effective at the stage of normoalbuminuria or microalbuminuria in both type I and type II diabetics with the II genotype, whereas the DD genotype is associated with a better response to ARA therapy in overt nephropathy of type II diabetes and to ACE inhibitors in male patients with nondiabetic proteinuric nephropathies. The role of other RAS or non-RAS polymorphisms and their possible interactions with different ACE I/D genotypes are less clearly defined. Thus, evaluating the ACE I/D polymorphism is a reliable tool to identify patients at risk and those who may benefit the most of renoprotective therapy with ACE inhibitors or ARA. This may guide pharmacologic therapy in individual patients and help design clinical trials in progressive nephropathies. Moreover, it might help optimize prevention and intervention strategies at population levels, in particular, in countries where resources are extremely limited and 1 million patients continue to die every year of cardiovascular or renal disease.
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PMID:Angiotensin converting enzyme insertion/deletion polymorphism and renoprotection in diabetic and nondiabetic nephropathies. 1855 Jun 51

The incidence of end-stage renal disease (ESRD) has been increasing, and within a 10-year period it is predicted that it will increase by 40 %. The main cause of death in this population of more than 50,000,000 individuals worldwide is cardiovascular disease. Increased urinary albumin is a predictor of renal failure, type 1 and type 2 diabetes; it correlates closely with mean arterial pressure in hypertensive subjects, predicts cardiovascular events and has a strong association with the metabolic syndrome. Treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers can reduce progressive renal damage, the beneficial effect being partially independent of the blood pressure lowering actions. Various therapies have proved effective in reducing microalbuminuria and progressive renal damage, demonstrating that the risk factor associated with a clinical outcome decreases with appropriate treatment. Cardiovascular events are the main cause of death in most patients with chronic renal disease. Diabetes, hypertension, obesity and smoking further increase the likelihood of vascular damage. Screening target populations of people with diabetes or hypertension is well recognized. Studies in several countries that have tested for albuminuria in unselected populations have demonstrated associations between microalbuminuria and deteriorating renal function, with the risk of developing ESRD and cardiovascular outcomes. There is some evidence for the use of urinary albumin as a marker of kidney involvement in unselected populations, but this needs to be strengthened and it may be cost effective compared with no screening. This has the potential to have a major impact in developing countries facing the challenges of chronic kidney disease, diabetes and cardiovascular disease.
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PMID:Evidence for the use of urinary albumin as marker of kidney involvement in unselected populations. 1856 65

The Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) study previously showed that treatment with telmisartan, an angiotensin II receptor blocker, effectively reduced the transition from incipient to overt nephropathy in Japanese type 2 diabetic patients. However, that large study included both normotensive and hypertensive patients. In the present post hoc analysis, we aimed to assess whether or not telmisartan elicits beneficial effects on the progression of microalbuminuria in normotensive patients. We randomized 163 microalbuminuric (urinary albumin-to-creatinine ratio: UACR of 100 to 300 mg/g creatinine) normotensive type 2 diabetic patients to treatment with telmisartan (40 or 80 mg once daily) or placebo over 52 weeks. The patients treated with either dose of telmisartan showed lower transition rates from microalbuminuria to overt nephropathy compared to the placebo group. In addition, more patients on telmisartan reverted to normoalbuminuria (UACR<30 mg/g creatinine): 15.5% of the 40 mg group, 19.6% of the 80 mg group, and 1.9% of the placebo group. In normotensive patients treated with telmisartan, changes in UACR were not significantly correlated with changes in blood pressure. Side effects did not differ among the groups. The present study demonstrates that telmisartan prevents the progression of microalbuminuria (in some cases induces remission of albuminuria) in normotensive Japanese patients with type 2 diabetes. Telmisartan is shown to be safe and well tolerated in these patients.
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PMID:Microalbuminuria reduction with telmisartan in normotensive and hypertensive Japanese patients with type 2 diabetes: a post-hoc analysis of The Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) study. 1863 77

Azelnidipine has been reported to have antioxidant effects and attenuates tubulointerstitial ischemia. The aim of the present study was to determine whether azelnidipine exerts additional renoprotective effects to angiotensin II receptor blockers (ARBs) in hypertensive patients with diabetic nephropathy and microalbuminuria. 45 hypertensive patients with diabetes mellitus and microalbuminuria who were already being treated with ARBs were enrolled in this study. Azelnidipine was added to the drug treatment of 30 patients (8 mg/day, n = 15, or 16 mg/day, n = 15) whilst the remaining 15 control patients were not treated with azelnidipine. In all patients, urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and urinary liver-type fatty acid-binding protein (L-FABP) levels were significantly correlated (r = 0.587, p = 0.0006). However, urinary albumin excretion (UAE) was not correlated with the levels of urinary 8-OHdG (r = 0.1975, p = 0.2956) or urinary L-FABP (r = 0.2057, p = 0.2759). Azelnidipine significantly reduced UAE, urinary 8-OHdG and urinary L-FABP after 6 (p < 0.05) and 12 months (p < 0.05). Although blood pressure was comparable between the azelnidipine doses of 8 and 16 mg/day, the UAE (p < 0.05 after 12 months), urinary 8-OHdG (p < 0.05 after 6 and 12 months) and urinary L-FABP (p < 0.05 after 6 and 12 months) levels were more significantly reduced in patients receiving the higher dose of 16 mg/day. These data may suggest that the addition of azelnidipine treatment to therapy with ARBs has dose-dependent antioxidant and renoprotective effects beyond blood pressure-lowering effects in hypertensive diabetic nephropathy patients.
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PMID:Additional renoprotective effects of azelnidipine combined with angiotensin receptor blockers in patients with diabetic nephropathy. 1900 May 38


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