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)

Diabetic nephropathy is the single most common cause of end-stage renal disease in the United States. Recently, several major therapeutic interventions have been developed and demonstrated to slow or halt the progression of renal failure in patients with diabetes and diabetic kidney disease. The Diabetes Control and Complications Trial demonstrated that microalbuminuria developed in fewer patients in the intensive blood sugar control group than in the conventional therapy group. Similarly, the risk of developing proteinuria was reduced by intensive blood sugar control. Multiple studies have demonstrated that in patients with insulin-dependent diabetes and proteinuria, lowering the systemic blood pressure slows the rate of decline in renal function and improves patients' survival. In the recently completed trial of ACE inhibition in diabetic nephropathy, ACE inhibitors were specifically shown to decrease dramatically the risk of doubling of serum creatinine or reaching a combined outcome of end-stage renal disease or death. In studies in small numbers of patients with insulin-dependent diabetes and established diabetic nephropathy, dietary protein restriction has also been demonstrated to slow the rate of decline of renal function. New potential interventions currently undergoing study include the use of aldose reductase inhibitors, the use of drugs that prevent the formation of advanced glycosylation end-products, and the use of angiotensin II receptor antagonists. Thus, several established benefits have recently been demonstrated to help prevent the development of or slow the progression of diabetic nephropathy, including blood pressure control, blood sugar control, and treatment with ACE inhibitors. Dietary protein restriction may also be of benefit. Multiple new interventions are undergoing clinical trials currently.
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PMID:Medical management of nephropathy in type I diabetes mellitus: current recommendations. 874 76

Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in the United States, and accounts for 35% of all the patients with ESRD entering a dialysis program; 63% of patients with diabetic nephropathy have type II diabetes mellitus. Hypertension is a major risk factor for renal disease and is common in people with diabetes mellitus. Strategies for preventing the progression of renal failure in patients with diabetes mellitus include glycemic control, and control of blood pressure. Blocking the renin-angiotensin system (RAS) slows the progression of established diabetic nephropathy in type I diabetes mellitus, and inhibiting angiotensin II formation retards or impedes the progression from microalbuminuria to established diabetic nephropathy (macroproteinuria) in people with type I diabetes mellitus. The situation could be the same for people with type II diabetes mellitus. The ability of RAS blockade using irbesartan, an AT1 angiotensin II receptor antagonist, to slow the progression in renal failure has been compared with that of the calcium channel blocker amlodipine and placebo in a pilot study. The results suggest that blockade of the RAS, in this case with irbesartan, is at least equivalent to calcium channel blockers with respect to antihypertensive efficacy, but provides better renoprotective benefits.
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PMID:Renoprotection and renin-angiotensin system blockade in diabetes mellitus. 943 77

Increasing worldwide rates of diabetes mellitus, combined with the significant micro- and macrovascular complications that accompany the disease, point to a heightened need to develop simple, rational strategies to protect against end-organ damage, particularly diabetic nephropathy. Although simple strategies do exist, i.e., early diagnosis of microalbuminuria (MAU) followed by nephroprotective therapy with angiotensin-converting enzyme (ACE) inhibitors, the use of these techniques should be increased. This is especially true for primary care physicians, who will continue to handle the majority of diabetic patients. To combat the underuse of this dual approach, this article reviews a stepwise approach to identifying early MAU so that therapeutic measures can be undertaken before the disorder progresses to diabetic nephropathy and, consequently, to end-stage renal disease in the majority of patients. Once a diagnosis of MAU is made, a variety of trials have demonstrated that ACE inhibitor therapy should be considered the standard therapy to retard worsening albuminuria and subsequent renal disease. ACE inhibitors can retard the progression of microalbuminuria and can lower the percentage of patients who progress to end-stage renal disease and death. Significant data indicate that ACE inhibitors should be used in MAU diabetics regardless of the level of blood pressure. In particular, the ACE inhibitor fosinopril may offer advantages because of its dual route of elimination, thus simplifying dosing in renally impaired patients. The newly developed angiotensin II receptor antagonists should be considered in patients intolerant to ACE inhibitors because of the similar effect on the interruption of the renin-angiotensin system.
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PMID:Relationships among diabetes, microalbuminuria, and ACE inhibition. 973 36

During the last few years there has been a renewed interest in blood-pressure (BP)-induced kidney damage, owing to a progressive increase in the incidence and prevalence of hypertension and vascular diseases as a cause of end-stage renal disease (ESRD). The need to prevent ESRD demands continued efforts so as to identify early those people with hypertension who are at risk and to provide them with effective antihypertensive therapy. This review analyses what is needed in terms of surrogate endpoints for monitoring kidney damage and what is known about the impact of antihypertensive treatments in reducing the BP burden on the kidney in non-diabetic subjects. Although glomerular filtration rate (GFR) and proteinuria are useful surrogate endpoints for patients with nephropathy and GFR below or close to the threshold value for renal insufficiency, it is clear that monitoring changes in either GFR or proteinuria does not provide a sensitive endpoint for subjects with the mildest forms of renal disease, e.g. essential hypertensive patients who are at risk of developing kidney damage. In this case microalbuminuria may be useful, although unequivocal evidence demonstrating that microalbuminuria is a risk marker for developing renal insufficiency in non-diabetic renal diseases has not existed until now, and whether a decrease in microalbuminuria is of prognostic significance in patients with essential hypertension remains to be demonstrated. The beneficial effects of the antihypertensive agents on microalbuminuria are also proportional to BP reduction. If a large enough BP reduction is achieved there seem to be, at most, only minimal differences among the antihypertensive drug classes. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have additional beneficial effects on microalbuminuria independent of the BP reduction, owing to their direct role in glomerular haemodynamics. The heterogeneity in the changes in urinary albumin excretion during antihypertensive treatment may be related to the different factors involved in the presence of microalbuminuria or structural end-organ damage, or both.
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PMID:Renal protection by antihypertensive drugs: insights from microalbuminuria studies. 988 2

The objective of this study was to analyze the relationship of polymorphisms of the angiotensin II AT1 receptor gene with microalbuminuria in a group of young adults with essential hypertension. Essential hypertensives, less than 50 years old, never previously treated with antihypertensive drugs, and in absence of diabetes mellitus were included. Office blood pressure (BP), 24-h ambulatory BP monitoring, urinary albumin excretion (UAE) measurements, and DNA analysis were performed. Polymorphisms of the angiotensin II AT1-receptor gene (A1166C and C573T) were studied by polymerase chain reaction and single-strand conformation polymorphism techniques. One hundred eighty-three patients, 49 (27%) microalbuminurics, were included. Office and ambulatory BP values were significantly higher in the microalbuminuria group. No differences in the presence of microalbuminuria were observed among the genotypes of either A1166C or C573T polymorphisms of the angiotensin II receptor AT1 gene, or in the allele frequency of the A1166C or the C573T polymorphism. LogUAE was significantly different among genotypes of the C573T polymorphism [CC 1.30(1.15-1.45), CT 1.14(1.00-1.28), and TT 0.94(0.68-1.20), P < .05]. Both office and ambulatory blood pressure and the TT/C573T genotype were independently related to logUAE, and, at the same BP values, UAE was lower in subjects with this genotype. We have found that the C573T polymorphism is on linkage disequilibrium with A1166C, as the 573T allele is closely linked to the presence of the 1166A allele, but not vice versa. Haplotype analysis among subjects with the AA genotype for the A1166C polymorphism confirms the influence of the TT genotype of the C573T polymorphism on the UAE in hypertensives. The C573T polymorphism of the angiotensin II receptor AT1 gene seems to be a genetic protective factor for UAE in a population of essential hypertensives.
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PMID:Angiotensin II AT1 receptor gene polymorphism and microalbuminuria in essential hypertension. 1133 83

Diabetic nephropathy has become the leading cause of terminal renal failure in all Western nations due to a steady increase of patients with the renal complication of type 2 (non-insulin-dependent) diabetes mellitus. A number of modifiable risk factors have been identified that predispose to and/or accelerate renal disease in patients with diabetes mellitus. Among these, the level of blood pressure, even in the range of normotension according to World Health Organization or Joint National Committee definition, is closely related to the rate of progression of diabetic nephropathy. This has been documented in patients with incipient (microalbuminuric) and in patients with manifest (proteinuric) diabetic renal disease. Consequently, the treatment of even normotensive diabetics has been recommended once microalbuminuria is present, and blood pressure values in the low normal range should be aimed for. The selection of antihypertensive agents is also important, however, since a 'renoprotective effect' has been documented for drugs that interfere with the renin-angiotensin-aldosterone system such as angiotensin converting enzyme inhibitors. Recently, a new class of drugs that selectively inhibits this system by specifically targeting the angiotensin II receptor has been developed. These angiotensin II subtype 1-receptor antagonists are efficacious antihypertensive agents with a side-effect profile similar to placebo. Evidence for a renoprotective effect in patients with diabetic nephropathy from a large controlled clinical trial is still awaited, but data generated in animal experiments and in smaller clinical trials are encouraging. Currently, these drugs are a valuable substitute for angiotensin converting enzyme inhibitors in patients who experience side effects such as intractable cough.
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PMID:Angiotensin II subtype 1-receptor antagonists in the treatment of diabetic nephropathy. 1145 Dec 16

Cardiovascular and renal diseases in diabetes stem from an accelerated form of atherosclerosis in both small and large blood vessels. Diabetic nephropathy is a clinical hallmark of microangiopathy and often leads to end-stage renal failure. Significantly, microalbuminuria is an independent predictor of cardiovascular morbidity and mortality in both the diabetic and non-diabetic population. In diabetic patients, it is also strongly associated with proliferative retinopathy, neuropathy and hypertension. Effective blood pressure reduction in patients with type 2 diabetes and diabetic nephropathy is known to reduce albuminuria, delay the progression of diabetic nephropathy, postpone renal failure and improve survival. These benefits have been demonstrated with a variety of blood pressure-lowering agents, including beta-blockers, calcium channel blockers, diuretics and angiotensin-converting enzyme (ACE) inhibitors. Less is known about the renal effects of the newest class of antihypertensive agents, the angiotensin II receptor antagonists (AIIRAs). Irbesartan is an AIIRA that provides antihypertensive efficacy comparable to ACE inhibitors but with superior tolerability. The PRogram for Irbesartan Mortality and morbidity Evaluations (PRIME) is an important morbidity and mortality program encompassing the Irbesartan Diabetic Nephropathy Trial (IDNT) and the IRbesartan MicroAlbuminuria type 2 diabetes mellitus in hypertensive patients (IRMA II) study. PRIME is evaluating the effects of irbesartan in preventing diabetic nephropathy and end-stage renal failure and in reducing cardiovascular events in high-risk hypertensive patients with type 2 diabetes. The trials were completed at the end of 2000.
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PMID:Hypertension and diabetes: the scope of the problem. 1146 14

We compared the efficacy of treatment protocols with an angiotensin converting enzyme (ACE) inhibitor alone (enalapril, 5 mg) or angiotensin II (ATII) receptor blocker (losartan, 50 mg) or both enalapril plus losartan in patients with microalbuminuria in a prospective, randomized clinical trial. Normotensive type 2 diabetic patients with microalbuminuria documented by at least 3 consecutive urinary albumin excretion analyses were recruited for the study. Patients were grouped randomly into one of the protocols which consisted of treatment with 5 mg enalapril daily (group 1; n=12), 50 mg losartan daily (group 2; n=12) or both drugs (group 3; n=10). They were reevaluated with regard to HbA1c levels, lipid profiles, blood pressure and urinary albumin excretion rates (UAER) at 3-month intervals for 12 months. Mean age, duration of diabetes, body mass index, plasma lipid profiles and blood pressure levels were similar at the initial visit. In group 1, UAER returned to normal levels in 10 patients. Normalization of UAER occurred in 8 and 7 patients in groups 2 and 3, respectively. Percentage of reduction in UAERs at the end of 12 months were 58%, 59% and 60% (p=0.0001; p=0.0002; p=0.0003, respectively). The amount of reduction in UAER did not differ significantly among the three groups (p=0.346). ACE inhibitors and angiotensin II receptor blockers have similar efficacy in treating diabetic microalbuminuria, and the combination of the two drugs does not add any further benefit.
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PMID:Efficacy of ACE inhibitors and ATII receptor blockers in patients with microalbuminuria: a prospective study. 1185 93

The DETAIL (diabetics exposed to telmisartan and enalapril) study will compare the long-term renal outcome of treatment with the angiotensin II receptor antagonist (ARA) telmisartan versus the angiotensin-converting enzyme (ACE) inhibitor enalapril in patients with mild-to-moderate hypertension and diabetic nephropathy. In short-term clinical studies, ACE inhibitors reduce microalbuminuria and, in the longer term, they are superior to conventional therapies in maintaining normal renal function. ARAs also appear to be renoprotective in diabetic animals. In this double-blind, parallel-group study, 252 patients with Type 2 diabetes and concurrent hypertension (mean seated systolic blood pressure < or = 180 mm Hg, on treatment seated diastolic blood pressure < or = 95 mm Hg) have been randomised to once-daily telmisartan 40 mg or enalapril 10 mg; doses are mandatorily titrated to 80 and 20 mg once daily, respectively, after 4 weeks. The primary endpoint will be the change from baseline in glomerular filtration rate (GFR) after 5 years of therapy, using the iohexol method and central laboratory analysis. The secondary endpoints to be evaluated will be: changes in GFR in relation to baseline after 1-4 years of therapy; percentage changes in albumin excretion rate after 1-5 years; and incidences of end-stage renal disease, cardiovascular events, all-cause mortality, and adverse events. The planned date for the completion of the study is 2005.
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PMID:Rationale and design of diabetics exposed to telmisartan and enalapril (DETAIL) study. 1201 88

To evaluate the efficacy of angiotensin II receptor blockers (ARBs) for use in the treatment of diabetic nephropathy, we examined the effects of olmesartan medoxomil (olmesartan), an angiotensin II type 1 (AT1) specific ARB, on the progression of nephropathy in Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. We used 2 doses of olmesartan, a sub-antihypertensive dose and an antihypertensive dose, to specifically examine whether the drug exerts beneficial effects on the kidney without lowering blood pressure. Olmesartan mixed in the diet at a concentration of 0.001% (approximately 0.6 mg/kg/day) or 0.01% (approximately 6 mg/kg/day) was administered for 19 weeks starting from 12 weeks of age, when the animals developed microalbuminuria. Lean non-diabetic rats served as controls. ZDF rats had hyperglycemia, hyperinsulinemia, and moderate hypertension as compared to lean control rats. Plasma glucose and insulin concentrations were not affected by olmesartan, and blood pressure was lowered only by the high dose of olmesartan. Progressive proteinuria in ZDF rats was greatly (about 70%) suppressed by the high dose of olmesartan and moderately (about 30%) suppressed by the low dose that did not significantly lower blood pressure. ZDF rats exhibited hyperlipidemia and hypoalbuminemia, both of which were substantially corrected by treatment with olmesartan. The histological evidence of glomerular and tubular damage in the ZDF rats was also reduced by the drug. These results indicate that AT1 receptor blockade with olmesartan retards the progression of nephropathy associated with type 2 diabetes without affecting glucose metabolism, and that this renal protective effect is at least partly independent of the antihypertensive effect of the drug.
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PMID:Renoprotective effects of blockade of angiotensin II AT1 receptors in an animal model of type 2 diabetes. 1204 43


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