UMLS:C0730345 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0730345 (microalbuminuria)
4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated therapeutic effects of a rapid- and short-acting non-sulfonylurea hypoglycemic agent, calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate dihydrate (KAD-1229), on streptozotocin (STZ)-induced non-insulin-dependent diabetes mellitus (NIDDM) rats. The effects exerted by KAD-1229 on the post-prandial plasma glucose rise in STZ-induced mild NIDDM (mNIDDM) rats were different from those of sulfonylureas. When KAD-1229 with liquid meal (10 kcal/kg) was given to the mNIDDM rats, the plasma glucose migration was similar to that of normal healthy rats. On the contrary, glibenclamide had little or no effect on the plasma glucose rise 0.5-1 hr after oral administration, and its effect was only evident 2-5 hr after dosing. Tolbutamide showed similar hypoglycemia to that induced by glibenclamide at 2-5 hr with insufficient efficacy at 0.5 hr. Gliclazide sufficiently suppressed the level of post-prandial plasma glucose. However, its complete inhibition of post-prandial plasma glucose was associated with the extra-hypoglycemia 1-5 hr after oral administration. We also tested the efficacy of KAD-1229 in more severe STZ-induced NIDDM (sNIDDM) rats to elucidate the effects of the drug on the long-term glycemic controls and diabetic complications. When the sNIDDM rats were treated with 10 mg/kg KAD-1229 twice a day for about 17 weeks, increases in fasting plasma glucose and hemoglobin A1c were inhibited. Furthermore, treatment with KAD-1229 suppressed the development of microalbuminuria and cortical cataract. We conclude that the rapid- and short-acting insulinotropic agent KAD-1229 is able to improve the deterioration in the glycemic controls and inhibit the development of diabetic complications in STZ-induced NIDDM rats.
...
PMID:A rapid- and short-acting hypoglycemic agent KAD-1229 improves post-prandial hyperglycemia and diabetic complications in streptozotocin-induced non-insulin-dependent diabetes mellitus rats. 888 29

The objectives of this study were to evaluate the effects of an ACE inhibitor (fosinopril) and a calcium antagonist (amlodipine) on the urinary albumin and transferrin excretion and their relationship to the blood pressure in essential hypertension. Twenty-four never-treated patients (mean age, 46.4 +/- 8.9 years) with a diastolic blood pressure between 90 and 114 mm Hg and normal renal function, randomly received amlodipine or fosinopril and, if the diastolic blood pressure was not normalized, doxazosin was added to the therapy. Twenty-four-hour ambulatory blood pressure monitoring and 24-h urine collection for albumin and transferrin measurements were performed before and after 3 and 6 months of therapy. Diastolic blood pressure was normalized in 23 patients (96%). Before treatment, microalbuminuria was present in 50% of patients. In the amlodipine and fosinopril group, antihypertensive therapy significantly decreased blood pressure and, only in the fosinopril group, albuminuria. Transferrinuria did not change significantly in both groups. Fosinopril lowered albuminuria in all patients, whereas amlodipine only in half of patients. Albuminuria, but not transferrinuria, was significantly correlated to the ambulatory blood pressure. This correlation was more pronounced for systolic than for diastolic pressure. In essential hypertensive patients with normal renal function, a high prevalence of microalbuminuria can be observed. Albuminuria appears to correlate with ambulatory blood pressure, particularly with systolic pressure. Intrarenal hemodynamic changes seem to play a more important role than systemic blood pressure decrease in the reduction of albuminuria. Transferrinuria does not seem a useful marker to follow-up nondiabetic hypertensive patients with early signs of glomerular dysfunction.
...
PMID:Albuminuria and transferrinuria in essential hypertension. Effects of antihypertensive therapy. 893 31

Renal disease in elderly diabetic patients is costly in terms of morbidity, mortality and medical payments. Therefore, prevention of diabetic nephropathy has become a prominent goal in the treatment of diabetic patients. Preventive treatment should begin not later than at the stage of persistent microalbuminuria, and regular screening for microalbuminuria is recommended for both elderly and younger diabetic patients. Improved metabolic control, through diet and hypoglycaemic therapy, has been demonstrated to lower urinary albumin excretion. The target level of glycated haemoglobin is < 8%, or < 2% higher than the upper limit of normal in nondiabetic people. Insulin therapy has no adverse effects on renal indices, unless it increases bodyweight and consequently raises blood pressure. To preserve renal function in elderly diabetic patients, blood pressure should be kept well below 140/90 mm Hg. Treatment with ACE inhibitors may be the 'gold standard' intervention, and should be initiated at the lowest possible dosage and then titrated until the maximum tolerated dosage has been reached. Nonchronotropic calcium antagonists have been shown to be as effective as ACE inhibitors with regard to their effects on blood pressure, renal haemodynamics and urinary albumin excretion. Most dihydropyridines have been found to increase or to have no effect on urinary albumin excretion despite significant blood pressure reduction. A renoprotective action of diuretics is generally unlikely, with the possible exception of indapamide. Although beta-blockers are effective antihypertensive agents, they may not adequately preserve kidney function in diabetic patients. Because beta-blocker treatment may mask the symptoms of hypoglycaemia, they should be reserved for patients with coronary artery disease or arrhythmias.
...
PMID:Chemoprophylaxis of diabetic nephropathy in the elderly. 897 44

This study aimed to investigate the relationship between microalbuminuria and office blood pressure (BP) as compared with ambulatory BP in patients with diabetes mellitus under everyday practice conditions. It was also undertaken to assess the effect of the angiotensin converting enzyme inhibitor cilazapril on diabetes-associated albuminuria. Ambulatory BP was recorded during daytime in 54 patients with type II diabetes mellitus at the end of a 4-week period during which they received no vasoactive drug. The difference between office and ambulatory BP was unpredictable in the individual patient. There was no significant correlation between either ambulatory or office BP and urinary albumin/p5eatinine ratio. Fifty-one patients underwent a 40-week treatment with 5 mg/day of cilazapril. There was, in the absence of satisfactory BP control, the possibility of adding the calcium antagonist amlodipine (5 mg/day) from the 10th week onward and 12.5 mg/day of hydrochlorothiazide from the 20th week onward. Office mean BP was significantly reduced after 30 to 40 weeks of therapy in patients with normoalbuminuria (n = 19, -14%, P < .001), in those with microalbuminuria (n = 22, -6.6%, P < .01), as well as in those with clinical proteinuria (n = 9, -11.4%, P < .01). During the same time, the urinary albumin/creatinine ratio was not modified in normoalbuminuric patients (n = 19, +24.6%, P = .72) as well as in those with clinical proteinuria (n = 9, -29.4%, P = .09). On the other hand this value was significantly reduced for the group with microalbuminuria (n = 23, -24.3%, P < .05). In the overall population, as well as in hyperalbuminuric patients (patients with microalbuminuria + patients with clinical proteinuria), the reduction of the albumin/ creatinine ratio was also significant (n = 51, -7%, P < .01 and n = 32, -25,7%, P < .01, respectively). In conclusion, the findings of this study performed by practicing physicians show that ambulatory BP may differ greatly from office BP in diabetic patients. They also indicate that urinary albumin excretion is poorly correlated with office and ambulatory BP in type II diabetics. Finally, they demonstrate the antiproteinuric action of prolonged treatment with the angiotensin converting enzyme inhibitor cilazapril, whether given alone or combined with amlodipine.
...
PMID:Albuminuria in diabetes mellitus: relation to ambulatory versus office blood pressure and effects of cilazapril. 897 94

1. Whether an alteration in cell membrane cation transport after exposure to insulin and angiotensin II (two important growth promoters that have been shown to be involved in the pathogenesis of atherosclerosis and hypertension) is present in cells from non-insulin-dependent diabetes patients with microalbuminuria, a known risk factor for cardiovascular and renal disease, is unknown. We therefore examined intracellular pH and calcium changes after acute exposure to insulin and angiotensin II in cultured skin fibroblasts from eight non-insulin-dependent diabetes patients with and eight others without microalbuminuria and from a group of seven matched, normal control subjects. 2. Cultured fibroblasts were loaded with 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester or fura 2-acetoxymethyl ester for continuous monitoring of intracellular pH and free calcium concentrations respectively. 3. In quiescent growth-arrested cells, both intracellular pH and free calcium concentrations were similar in the three groups of subjects. Acutely, insulin induced a gradual alkalinization in all groups of patients. The pH increase was significantly greater in non-insulin-dependent diabetes mellitus patients with microalbuminuria (delta pH +0.24 +/- 0.04 pH units) than in normoalbuminuric patients with non-insulin-dependent diabetes mellitus (0.08 +/- 0.02; P < 0.01) and normal control subjects (0.05 +/- 0.01; P < 0.01). Although the alkalinizing effect of angiotensin II was smaller than that obtained by insulin, intracellular pH increase after angiotensin addition was more pronounced in non-insulin-dependent diabetes mellitus patients with microalbuminuria (delta pH +0.14 +/- 0.04 pH units) than in those without (0.08 +/- 0.02; P < 0.01) and in normal control subjects (0.02 +/- 0.02; P < 0.01). That the increase in intracellular pH was mediated by the sodium-hydrogen antiport was demonstrated by its dependence on the presence of sodium in the medium and its inhibition by amiloride. Whereas insulin addition did not evoke any significant increase in intracellular free calcium levels in fibroblasts from the three groups studied, angiotensin II evoked a fast and transient rise in intracellular free calcium that was higher in fibroblasts from microalbuminuric patients with non-insulin-dependent diabetes mellitus than in cells from normoalbuminuric patients with non-insulin-dependent diabetes mellitus and control subjects. In the whole population of patients with non-insulin-dependent diabetes mellitus, the increase in intracellular pH after exposure to angiotensin II was positively correlated with intracellular free calcium increase (r = 0.53; P < 0.05), suggesting a possible role of intracellular free calcium levels in the activation of the sodium-hydrogen antiport. 4. In conclusion, we have described an association between increased agonist-induced responsiveness of sodium-hydrogen antiport activity and the presence of microalbuminuria in patients with non-insulin-dependent diabetes mellitus. This increased responsiveness, persisting in cultured fibroblasts after several passages in vitro, suggests that in vitro phenotypic characteristics of fibroblasts are likely to be genetically determined and to be, at least in part, independent of the degree of metabolic control in vivo.
...
PMID:Enhanced effects of insulin and angiotensin II on intracellular pH and free cytosolic calcium in fibroblasts from microalbuminuric patients with non-insulin-dependent diabetes mellitus. 897 5

The combination of diabetes and hypertension increases the changes of progressive renal disorder and ultimately renal failure. Roughly 40% of all diabetics, whether insulin dependent or not, develop diabetic nephropathy. Diabetic nephropathy is the single most important cause of end-stage renal disease in the western world and accounts for more than a quarter of all end-stage renal diseases. It is also a major cause of increased morbidity and mortality in diabetic patients. Increased arterial blood pressure is an early and common phenomenon in incipient and overt diabetic nephropathy. The relationship between arterial blood pressure and diabetic nephropathy is a complex one, diabetic nephropathy increasing blood pressure and blood pressure accelerating the course of nephropathy. Calcium antagonists antagonize preglomerular vasoconstriction. Furthermore, additional putative mechanisms include the ability to retard renal growth and possibly to attenuate mesangial entrapment of macromolecules and to attenuate the mitogenic effects of diverse growth factors. Calcium antagonists (except the old short-acting dihydropyridine drugs) reduce microalbuminuria and preserve kidney function in diabetic patients with incipient diabetic nephropathy. Long-term trials using the new long-acting dihydropyridine calcium antagonists for the treatment of patients with incipient nephropathy are still lacking. A recent 1-year randomized double-blind study in hypertensive insulin-dependent diabetic patients with diabetic nephropathy showed a more beneficial effect on the decline rate in the glomerular filtration rate of nisoldipine (long-acting dihydropyridine) than angiotensin-converting-enzyme (ACE) inhibition. The mean arterial blood pressure during the study based on 24-hour recordings was nearly identical, 103 (SD 9) and 101 (SD 11) mm Hg in the two groups. Furthermore, a recent 5-year randomized open study in hypertensive noninsulin-dependent patients with diabetic nephropathy has revealed the same beneficial effect of a calcium antagonist and ACE inhibition on the progression of nephropathy. In a third group treated with sympatholytic drugs, more than 50% of the subjects had a doubling of their creatinine as compared to less than 10% in the two other groups mentioned above. However, long-term studies are needed to consolidate these findings and expand them to insulin-dependent diabetic patients with diabetic kidney disease.
...
PMID:Renal protection in diabetes--an emerging role for calcium antagonists. 939 96

There has been increasing interest in the question of whether microalbuminuria can be used in the risk stratification of patients with essential hypertension. A cluster of cardiovascular and/or renal risk factors may be associated with microalbuminuria in hypertension. Despite this, prospective data about the potential role of microalbuminuria as a prognostic marker of cardiovascular and/or renal risk have been sparse and inconclusive until now. Blood pressure values have been considered the most important determinant of microalbuminuria in essential hypertension; however, hyperinsulinaemia--a metabolic component-was noted to be present in conjunction with high blood pressure. Furthermore, 2 other factors may be also related to microalbuminuria: salt sensitivity and renal structural changes (nephrosclerosis). We are now aware that the clinical and physiological implications of abnormal urinary albumin excretion (UAE) are much broader than anticipated, possibly involving haemodynamic, metabolic and vascular components overlapping several clinical syndromes. Achievement of short term UAE reduction with antihypertensive treatment depends on structural abnormalities established in the glomerulus, the extent of blood pressure reduction and the antihypertensive drug class used. In terms of UAE reduction, better results are obtained with ACE inhibitors or angiotensin II antagonists such as losartan and valsartan, than with other antihypertensive classes, although their true impact in preserving renal function needs to be assessed. The capacity of new calcium antagonists, such as amlodipine, lacidipine or mibefradil, to reduce UAE also needs to be assessed further. Thus, microalbuminuria may be seen as an integrated marker of risk and should be assessed in recently diagnosed patients with essential hypertension. In microalbuminuric patients, the target should be to decrease blood pressure < 135/85 mm Hg, reduce salt intake to around 100 mmol/day and prescribe a low-calorie diet if obesity is present. ACE inhibitors or angiotensin II antagonists have more potential benefits than the other classes of antihypertensive drugs in reducing UAE. Finally, a yearly assessment of microalbuminuria is recommended during treatment, to monitor the impact of therapy.
...
PMID:Treatment of patients with essential hypertension and microalbuminuria. 942 93

The prevalence of abnormally elevated albumin excretion rate (> 30 mg/24 h) is approximately 40% in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients. Diabetes has become the leading cause of end-stage renal failure in the US, Japan and Europe. Approximately 90% of the direct and indirect cost of caring for diabetic patients are spent on the complications of diabetes. Identification of patients at high risk of developing diabetic nephropathy is possible by screening for microalbuminuria (30-300 mg/24 h). Elevated urinary albumin excretion rate indicates a substantially increased mortality risk in diabetic patients. Randomised controlled trials in normotensive IDDM and NIDDM patients with persistent microalbuminuria indicate that ACE inhibitors diminish urinary albumin excretion rate, postpone it and may even prevent progression to clinical overt nephropathy. These findings indicate that screening and intervention programs are likely to have life saving effects and lead to considerable economic savings. Systemic blood pressure elevation to a hypertensive level is an early and frequent phenomenon in diabetic nephropathy. Furthermore, nocturnal blood pressure elevation (non-dippers) occurs more frequently in patients with nephropathy. Systemic blood pressure elevation and to a lesser degree albuminuria accelerate the progression of diabetic nephropathy. Effective blood pressure reduction with non-ACE-inhibitors and/or ACE-inhibitors frequently in combination with diuretics: (a) reduces albuminuria; (b) delays the progression of nephropathy; (c) postpones renal insufficiency; and (d) improves survival in IDDM and NIDDM patients with diabetic nephropathy. A specific renal protective effect of ACE-inhibitors in diabetic nephropathy has been demonstrated in IDDM patients with moderately reduced kidney function (s-creatinine > 133 mumol/l) while the data conflict with NIDDM patients. Antihypertensive treatment for diabetic nephropathy simultaneously extends life and saves money. Finally, reduced risk of fatal and non-fatal cardiovascular events have been demonstrated when diabetic patients with isolated systolic hypertension are treated with blood pressure lowering agents. Absolute risk reduction with active treatment compared to placebo was twice as great for the diabetic versus non-diabetic patients (101/1000 versus 51/1000 randomised participants at the 5-year follow-up), reflecting the higher risk of diabetic patients. In conclusion, early detection and aggressive treatment of arterial hypertension with ACE-inhibitors, long acting calcium antagonist and low dose diuretics as first line drugs are highly warranted in diabetic patients with or without diabetic renal disease.
...
PMID:Is antihypertensive treatment the same for NIDDM and IDDM patients? 964 59

Recent trials in hypertensive patients with type 2 diabetes reveal important differences in the risk for major cardiovascular events when individual agents are compared. In the Fosinopril Amlodipine Cardiovascular Events Trial (FACET), 380 patients with hypertension and type 2 diabetes were randomized to fosinopril or amlodipine and followed for up to 3.5 years to assess effects on serum lipids. Although both agents effectively controlled blood pressure, amlodipine caused a significantly greater decrease in systolic pressure. At the end of the trial, serum cholesterol, high-density lipoprotein cholesterol, triglycerides, HbA1c, serum glucose, plasma insulin, serum creatinine, and microalbuminuria were similar in both groups. The patients randomized to fosinopril were significantly less likely to experience the prospectively defined combined outcome of acute myocardial infarction (MI), hospitalized angina, or stroke compared to those randomized to amlodipine (RR 0.49; 95% CI 0.26-0.95). In the Appropriate Blood pressure Control in Diabetes (ABCD) trial, 470 patients with hypertension and type 2 diabetes who were randomized to long-acting nisoldipine had an adjusted sevenfold increased risk for acute MI compared to those randomized to enalapril (RR 7.0; 95% CI 2.3-21.4). In the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) trial, the patients with hypertension and above the median of HbA1c (> or =6.7%) randomized to isradipine had a threefold increased risk for major cardiovascular events compared to those randomized to hydrochlorothiazide (RR 2.81; 95% CI 1.09-7.26). These findings are supported by several observational studies. Therefore, evidence is emerging that angiotensin-converting enzyme inhibitors and low-dose diuretics may be more effective than calcium antagonists for prevention of cardiovascular events in hypertensive patients with diabetes or impaired glucose control.
...
PMID:New evidence on the prevention of cardiovascular events in hypertensive patients with type 2 diabetes. 973 37

The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been investigated. The aim of the present study was to assess long-term renal function in children and adolescents who received at-risk chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg), phosphorus (P), and uric acid] were prospectively performed 5.4+/-2.2 (+/-SD) years after chemotherapy (total cumulative dose: methotrexate 41+/-31 g/m2, ifosfamide 39+/-14 g/m2, cisplatin 674+/-188 mg/m2) in 18 children and adolescents. The results were compared with 13 normal volunteers matched for age and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m2 in all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients. Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion of P, Mg, and uric acid was higher in patients than in controls. Glomerular function was not significantly altered and only mild tubular dysfunction was present. Since renal excretion of P and Mg were increased in patients compared with normal volunteers and hypercalciuria was occasionally seen, divalent ion disorders are the most-likely potential complications.
...
PMID:Long-term nephrotoxicity of cisplatin, ifosfamide, and methotrexate in osteosarcoma. 976 57

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>