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)

Renin plays a major role in the control of blood pressure and water and electrolyte metabolism and it is clear that blocking of this system is particularly effective in the treatment of essential hypertension and heart failure. A large number of converting enzyme inhibitors have been synthesized. Converting enzyme inhibitors are remarkably active in heart failure and they reduce microalbuminuria and possibly maintain glomerular function. Blocking of the renin-angiotensin system by converting enzyme inhibitors is not accompanied by hypotension or reflex stimulation of the sympathetic nervous system. Converting enzyme inhibitors represent a major therapeutic advance in the field of cardiovascular and renal disease but the long-term effects of decreased angiotensin II levels are unknown. There are other ways to inhibit the renin-angiotensin system. The recent discovery of orally-active non-peptide angiotensin II antagonists opens a range of fascinating prospects. Another approach consists in inhibiting the reaction of renin on angiotensinogen, which is remarkably selective. Although it is too early to know whether these new approaches will be less active, more active or as active as current converting enzyme inhibitors, they may constitute a progress in relation to currently available treatments.
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PMID:New therapeutic prospects of renin-angiotensin system inhibition. 269 Nov 25

Atrial natriuretic peptide (ANP) and the renin-angiotensin-aldosterone system are important regulatory hormones in sodium homeostasis. We have measured these hormones during volume expansion produced by water immersion in diabetic subjects without and with microalbuminuria or frank proteinuria and compared the response with normal controls. Diabetic subjects excreted about half the amount of sodium that was excreted by the normal subjects (39 vs 21 mmol) over 4 h. Diabetic subjects and normal ones showed a twofold rise in ANP during immersion and a marked suppression of both plasma renin activity and aldosterone. There was no difference in the hormonal response between diabetic and normal subjects or between those diabetic subjects with and those without incipient (microalbuminurics) or established nephropathy.
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PMID:The relationship of the renin-angiotensin-aldosterone system to atrial natriuretic peptide and the natriuresis of volume expansion in diabetics with and without proteinuria. 297 18

The hyperfiltration induced by an acute response to an oral protein and water load was investigated to ascertain whether it can modify the urinary albumin excretion (UAE) in the microalbuminuric range by further increasing the glomerular filter permeability. To this end, six patients with a single kidney selected as having microalbuminuria on a regular diet without the clinical or laboratory data of overt renal disease and eight healthy subjects received a short-term protein and water load (150 g of meat-derived protein and 1 liter of water). In patients with one kidney, mean basal UAE values were significantly higher than in control subjects (p less than 0.006), whereas endogenous creatinine clearance values were only slightly lower (p greater than 0.05). One hour after the protein and water load, an abrupt increase in microalbuminuria levels was found in patients with one kidney and mean UAE values were significantly higher than in control subjects (p less than 0.002), whereas mean creatinine clearance values were significantly lower in patients than in control subjects (p less than 0.01). High UAE (p less than 0.002) and low creatinine clearance (p less than 0.002) values were maintained over the following four hours in patients with one kidney. These data suggest that in the single kidney with reduced renal functional reserve, an oral protein and water load magnifies the pre-existing loss of glomerular permselective properties due to chronic hyperfiltration as manifested by a further increase in microalbuminuria.
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PMID:Single kidney function: effect of acute protein and water loading on microalbuminuria. 304 9

Recent studies have shown that both in hypertensives and in offspring of hypertensive parents there exists an altered renal functional reserve (RFR). The aim of this research was to study the RFR in newly diagnosed essential hypertensives, and to evaluate if any influences are played on RFR by circulating renin-angiotensin-aldosterone system, catecholamines, and plasma endothelin-1. In 16 essential hypertensives (EH) and in 10 healthy controls (C), on the 24-hour urine collection and on urine specimens taken after both an oral water load and an amino acids (AAs) infusion (4.16 ml/min for two hours), Ccr, microalbuminuria (AER) and its fractional clearance, and sodium excretion (Nau) were evaluated. Furthermore, both in basal condition and after the AAs load, blood samples were obtained to assay plasma renin activity (PRA) and aldosterone concentrations (PAC), circulating norepinephrine (NE) and endothelin-1 (ET-1). The C-group showed a mean increase in Ccr of 35%. No significant modifications in AER and in circulating hormones were observed. Among the 16 EH, thirteen subjects showed a significant increase in Ccr after the AAs load, with a mean increase of 32.5%. In the whole group of EH there were no significant differences in AER when comparing basal with after-load values, and Nau resulted significantly decreased after AAs infusion. The analysis of the hormonal pattern pointed out not significant changes in the behaviour of PRA, NE and ET-1, while a significant decrease in PAC was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The renal functional reserve in recently diagnosed essential hypertension. 802 14

There is experimental evidence that loss of renal parenchyma results in hyperfiltration in the remnant glomeruli followed by development of glomerulosclerosis. Microalbuminuria, i.e., a urinary albumin excretion rate of 20-200 micrograms/min, is considered to be an early predictor of diabetic glomerulosclerosis. Hypothetically, increased urinary albumin excretion in patients with pyelonephritic scarring may also indicate glomerulosclerosis, with risk for future deterioration of renal function. This study was performed to determine the incidence of increased albumin excretion in children with mild to moderate pyelonephritic scarring, and to relate the information to glomerular filtration rate (GFR; clearance of inulin) and effective renal plasma flow (clearance of para-aminohippuric acid), as well as to the degree of scarring. The functional investigations were performed under water diuresis. Fifty-seven children, aged 1.7-17.9 years, with pyelonephritic renal scarring were included in the study. Nine young healthy adults were used as controls. The GFR was significantly lower in the children with pyelonephritic scarring than in the controls (median 93 ml/min per 1.73 m2, range 48-133 vs. 111 ml/min per 1.73 m2, range 89-121, P < 0.05), and the urine albumin excretion was significantly higher (median 20 micrograms/min per 100 ml GFR, range 0.8-170 vs. 9.2 micrograms/min per 100 ml GFR, range 3.3-21, P < 0.05). An inverse correlation was found between urine albumin excretion and GFR. Increased urine albumin excretion was found in 70% of the children with a GFR below 90 ml/min per 1.73 m2 compared with 41% of the children with a GFR above this level. Increased urine albumin excretion (> 20 micrograms/min per 100 ml GFR) was found in 51% of the children with pyelonephritic scarring, while only 14% had increased age-adjusted serum creatinine concentrations. The high incidence of microalbuminuria in children with pyelonephritic scarring indicates long-term follow-up until the ultimate outcome has been better defined.
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PMID:Incidence of microalbuminuria in children with pyelonephritic scarring. 897 84

Relatively little is known of the chronic effects attributable to the ingestion of inorganic components such as uranium and silicon. Although ingestion of large amounts of U can cause acute renal damage through a chemical effect, studies on humans have typically considered inhalation the route of exposure. We investigated the association between drinking water concentration levels of U and Si, and microalbuminuria, a sensitive biological indicator of renal dysfunction. Linear regression analysis revealed a statistically significant association between U cumulative exposure index and albumin per mmol creatinine (P = 0.03). No such significant relationship appeared for Si, although a positive trend was witnessed. Since normal but increasing levels of microalbuminuria were observed at U concentration levels below the Canadian Maximum Allowable Concentration (MAC), it is suggested that further study be undertaken.
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PMID:Inorganic components of drinking water and microalbuminuria. 897 22

Proximal tubular dysfunction may be implicated in the pathogenesis of diabetic nephropathy. An investigation of proximal tubular function was carried out by assessing proximal tubular sodium-reabsorption and low molecular weight protein excretion in a group of patients with type 1 diabetes mellitus. Normoalbuminuric [group A, n = 6, albumin excretion rate (AER) mean (range) 4 (0-10) micrograms/min], and microalbuminuric [group B, n = 6, AER 88 (35-198) micrograms/min] patients with type 1 diabetes were compared with matched controls. Simultaneous lithium and growth hormone (GH) clearance and urinary beta 2-microglobulin excretion were assessed. Fasting plasma glucose at the start of the study was [median (range)] 13 (10.2-15.1), 9.3 (5.9-15) and 4.1 (4.0-5.0) mmol/l in groups A, B and controls, respectively, with a mean coefficient of variation during the study of 3.9% (group A) and 5.2% (group B). There was no significant difference in plasma glucose levels between patients in groups A and B. Urinary GH excretion was raised in the patients with microalbuminuria (group B; P < 0.05), although there was no difference in serum GH clearance rate between the patient groups and controls. Urinary GH correlated with B 2-microglobulin in the diabetic subjects (r = 0.665, P < 0.05) and with the degree of microalbuminuria in group B patients (r = 1, P < 0.01). Urinary GH was also greater than 10 microU, the median value observed in the controls, in 5 of 6 (83%) patients in group A. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) measured by constant infusion of 51Cr-ethylene diamine tetra-acetic acid (EDTA) and I125-para-amino hippuric acid (PAH), respectively, showed relative hyperfiltration in the normoalbumiruric group compared with controls (P < 0.05) and group B (P < 0.05). Absolute proximal reabsorption of sodium and of water (APRNa and APRH2O) was significantly higher in group A patients (P < 0.05). Although GFR was significantly higher in group A patients, no differences were found in fractional proximal reabsorption of sodium and water (FPRNa+H2O) or end proximal delivery between the patient groups and controls. Therefore, the measurement of protein reabsorptive capacity provides a more sensitive marker of renal tubular impairment in type 1 diabetes than sodium/fluid reabsorptive capacity. In patients with microalbuminuria, both glomerular and tubular damage may coexist. Our results stress the usefulness of markers of renal tubular function in monitoring the course of diabetic nephropathy. This study also shows that assessment of GH clearance has promise as a marker of renal tubular protein reabsorptive capacity.
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PMID:Proximal tubular reabsorption of growth hormone and sodium/fluid in normo- and microalbuminuric insulin-dependent diabetes mellitus. 913 54

Disturbances of coronary circulation have been reported in diabetic patients with microvascular complications but without obstructive coronary atherosclerosis. The aim of the present study was to investigate coronary flow reserve in young adult patients with IDDM but without microalbuminuria and diabetic autonomic neuropathy. Coronary flow reserve was determined in 12 nonsmoking male patients with IDDM (age 30.0 +/- 6.6 years) and 12 healthy matched volunteers. Groups were similar with respect to blood pressure and serum lipid concentrations, and no subject had a positive family history of coronary heart disease. The patients with IDDM had normal exercise echocardiography and autonomic nervous function tests. Five patients had minimal background retinopathy, and none had microalbuminuria. Positron emission tomography and [15O]H2O were used to measure myocardial blood flow at rest and after dipyridamole administration. The studies were performed during euglycemic hyperinsulinemia (serum insulin approximately 70 mU/l). The baseline myocardial blood flow was similar in patients with IDDM and in control subjects (0.84 +/- 0.18 vs. 0.88 +/- 0.25 ml x g(-1) x min(-1), NS). The myocardial blood flow during hyperemia was 29% lower in patients with IDDM (3.17 +/- 1.57) compared with the control subjects (4.45 +/- 1.37 ml x g(-1) x min(-1), P < 0.05). Consequently, coronary flow reserve (the ratio of flow during hyperemia and at rest) was lower in diabetic patients than in control subjects (3.76 +/- 1.69 vs. 5.31 +/- 1.86, P < 0.05) and the total coronary resistance during hyperemia was higher in diabetic patients (53.7 +/- 31.5) compared with the control subjects (31.4 +/- 11.6 mmHg x min x g x ml(-1), P < 0.05). The coronary flow reserve was similar in diabetic patients with and without mild background retinopathy. No association was found between the coronary flow reserve and serum lipid or HbA1c values in either group. Coronary flow reserve is impaired in young adult males with IDDM and no or minimal microvascular complications and without any evidence of coronary heart disease. This abnormality cannot be explained by standard coronary heart disease risk factors. The results imply early impairment of coronary vascular reactivity in IDDM patients, which may represent an early precursor of future coronary heart disease or may contribute to the pathogenesis of diabetic cardiomyopathy.
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PMID:Coronary flow reserve is reduced in young men with IDDM. 951 21

Raised plasma concentrations of atrial natriuretic peptide (ANP) have been reported in patients with Type 1 (insulin dependent) diabetes mellitus (DM) who have poor glycaemic control and are associated with the presence of microalbuminuria. To test the hypothesis that elevations in plasma ANP concentration increase urinary albumin excretion in Type 1 DM, we have studied the effects of intravenous infusions of ANP in eight such subjects with established microalbuminuria. Blood glucose was maintained between 4 and 7 mmol l-1 in all subjects for the duration of studies; after euglycaemia had been established, a standard oral water load (20 ml kg-1 plus replacement of urinary losses) was given. Once steady state diuresis was attained, subjects received intravenous infusion of either placebo (0.9% saline), low dose (2.5 pmol kg-1 min-1) or high dose (5.0 pmol kg-1 kg min-1) ANP solution in a randomized, double-blind protocol. Infusion of ANP caused a dose-dependent increase in urinary albumin excretion rate (placebo, 11.3 (SD 8.9) to 8.7 (SD 6.8) micrograms min-1; low dose ANP, 12.4 (SD 9.9) to 26.5 (SD 27.5) micrograms min-1, p < 0.01; high dose ANP 10.3 (SD 7.3) to 36.6 (SD 28.5) micrograms min-1, p < 0.001, ANOVA). Only high dose ANP caused an increase in urine flow. Blood glucose remained unchanged in all studies. We conclude that intravenous infusions of ANP cause a dose-dependent increase in urinary albumin excretion rate in Type 1 DM subjects with microalbuminuria. These data support the hypothesis that ANP has albuminuric actions which may contribute to microalbuminuria in Type 1 DM.
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PMID:Atrial natriuretic peptide increases urinary albumin excretion in men with type 1 diabetes mellitus and established microalbuminuria. 970 72

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE
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PMID:Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. 1085 85


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