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)

Roughly 40% of all diabetics, whether insulin dependent or not, develop persistent albuminuria, a decline in their glomerular filtration rate, and elevated blood pressure, i.e., diabetic nephropathy. Diabetic nephropathy is the single most important cause of end-stage renal disease in the Western world, accounting for over one-quarter of all end-stage renal disease. Systemic/glomerular hypertension plays a role in the initiation and progression of diabetic glomerulopathy. Angiotensin-converting enzyme (ACE) inhibitors are superior to conventional antihypertensive drugs in preventing the development of glomerular lesions in insulin-treated streptozotocin diabetic rats. Lowering of glomerular hypertension may be the crucial factor involved. Human studies suggest that ACE inhibitors postpone the progression to clinical overt diabetic nephropathy in normotensive diabetic patients with persistent microalbuminuria. ACE inhibitors combined with a diuretic reduce albuminuria and postpone renal insufficiency in hypertensive diabetics with overt nephropathy. No treatment modality other than antihypertensive treatment has yet been proven to be effective in protecting renal function in diabetic nephropathy. All previous reports dealing with the natural history of diabetic nephropathy have demonstrated a cumulative death rate between 50 and 77% 10 years after the onset of proteinuria. Effective antihypertensive treatment has reduced the cumulative death rate to 15-20% 10 years after the onset of nephropathy.
J Cardiovasc Pharmacol 1992
PMID:Renoprotective action of angiotensin-converting enzyme inhibition in diabetes mellitus. 138 60

The mechanism of the antiproteinuric effect of angiotensin-converting enzyme (ACE) inhibitors in diabetic and nondiabetic renal disease is as yet unknown. A meta-analysis of studies on the effects of ACE inhibitors and other antihypertensive drugs on proteinuria, blood pressure, and renal hemodynamics in nondiabetic renal disease revealed that ACE inhibitors lower proteinuria more than other antihypertensives. Moreover, a close correlation (p less than 0.01) between changes in urinary protein loss and in filtration fraction was found, whereas such a correlation could not be detected between changes in proteinuria and in blood pressure. This suggests that, at least in nondiabetic renal disease, the fall in proteinuria during ACE inhibition is the consequence of the intrarenal effect of the drug more than the systemic effect. Data on the mechanism of action of ACE inhibitors in diabetic microalbuminuria and in diabetic overt proteinuria are less consistent. A fall in proteinuria on antihypertensive drugs in these patients can be observed also without a significant fall in blood pressure, and without any change in filtration fraction. We therefore conclude that one should be cautious in extrapolating the data from studies in diabetic renal disease to patients with nondiabetic nephropathies. Moreover, we argue also that nonhemodynamic effects of ACE inhibitors also could be involved in the antiproteinuric effect of these drugs.
J Cardiovasc Pharmacol 1992
PMID:The antiproteinuric effects of blood pressure-lowering agents: differences between nondiabetics and diabetics. 138 62

Hypertension is frequently associated with insulin-dependent diabetes mellitus, but the mechanism of the hypertension is unknown. An animal model of insulin-dependent diabetes mellitus hypertension could be helpful in determining the mechanism, but experimental insulin-dependent diabetes mellitus has been infrequently and irregularly associated with hypertension. In an attempt to develop a dependable model of insulin-dependent diabetes mellitus hypertension, we studied seven series of rats receiving either streptozotocin, surgical reduction of renal mass, or both. We found that superimposing streptozotocin 65 mg/kg body weight on 25% reduced renal mass regularly produced insulin-dependent diabetes mellitus and low-renin volume-expanded hypertension and that the animals remained healthy and hypertensive for as long as followed (13 weeks). Microalbuminuria correlated temporally with blood pressure. We used this dependable model to examine the role of endogenous digitalis-like substance in the development of hypertension in insulin-dependent diabetes mellitus. Plasma levels of digoxin-like immunoreactive factor (DIF), determined with a digoxin radioimmunoassay, were significantly higher in these hypertensive rats than in normotensive control rats (two-kidney diabetic rats, 25% reduced renal mass rats receiving vehicle for streptozotocin). This increase in plasma DIF was associated with a decrease in Na+, K(+)-ATPase activity in microsomes prepared from left or right ventricle. Microsomal 5'-nucleotidase, a plasma membrane marker, was unchanged. The plasma DIF level correlated inversely with myocardial Na+, K(+)-ATPase activity and positively with systolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1993
PMID:Role of digitalis-like substance in experimental insulin-dependent diabetes mellitus hypertension. 750 18

Our aim was to assess the effect of blood pressure treatment on albumin excretion rate (AER) in diabetic patients using two antihypertensive agents with different modes of action: indapamide and captopril. Patients with persistent microalbuminuria on two occasions (AER 20-200 micrograms/min) entered a randomized crossover study of 12 weeks of therapy with a constant dose of either indapamide 2.5 mg daily or captopril 12.5 mg three times daily, with a 4-week washout between therapy periods. Blood pressure was measured using a random-zero sphygmomanometer and AER by radioimmunoassay on a timed urine collection. Results (mean +/- standard deviation) were analyzed by repeated measures of analysis of variance after log transformation of AER data. Twelve patients [nine men; mean age 58 +/- 7.5 years (range 49-73 years), all with non-insulin-dependent diabetes mellitus (NIDDM)] were studied. Both blood pressure [initial mean systolic 144 +/- 14 mm Hg (range 124-166)/initial mean diastolic 85 +/- 6 mm Hg (range 75-96)] and AER [initial 92 +/- 36 micrograms/min (range 36-161)] were significantly reduced below basal levels (at the 0.05 level) at all study intervals by both antihypertensive agents. The results show the importance of blood pressure and its treatment on AER in patients with NIDDM. In this study, indapamide was as effective as an angiotensin-converting enzyme inhibitor in reducing both blood pressure and microalbuminuria.
J Cardiovasc Pharmacol 1993
PMID:Regression of microalbuminuria: results of a controlled study, indapamide versus captopril. 750 65

Physical effort stimulates the reninangiotensin system (RAS). We studied the effect of an angiotensin-converting enzyme inhibitor (ACE inhibitor) in a double-blind placebo-controlled study, on eight volunteers undergoing physical stress on an ergometric bicycle. The effects of captopril (C) (50 mg, three times daily for 3 days) on arterial pressure (AP), O2 consumption (VO2), variations in auricular natriuretic factor (ANF), renin, angiotensin II (AII) plasma levels, as well as glomerular filtration rate (GFR) and microalbuminuria (MA) were evaluated. The different parameters were compared by analysis of variance (ANOVA). The pressure profile and VO2 were not modified by ACE inhibitor. Exercise stimulates release of renin; this action was greater with captopril administration (treatment effect: p < 10(-4), indicating blockade of the RAS. This inhibition was incomplete because AII levels increased markedly when captopril was given (no treatment effect: p < 0.37). Finally, ACE inhibitor resulted in decreased GFR (p = 115 +/- 5.8 ml/mn-1, C = 91.1 +/- 4, p < 0.05) with exercise without modification of MA. ACE inhibitor administration does not modify the physical performance of nonathletic subjects; AII is significantly increased with exercise despite captopril treatment; ACE inhibitor decreases GFR significantly but does not influence MA with prolonged physical effort.
J Cardiovasc Pharmacol 1993 Feb
PMID:Angiotensin-converting enzyme inhibition does not suppress plasma angiotensin II increase during exercise in humans. 767 64

We examined the renal hemodynamic modifications induced by a selective angiotensin II (AII) AT1 receptor antagonist, losartan, in 10 patients with essential hypertension. In this single-blind study, renal hemodynamic parameters were determined twice (patients were their own controls) first after a 15-day single-blind placebo run-in period and again after a 1-month losartan period. The dosage of losartan was 50 mg/day. Glomerular filtration rate (GFR, inulin clearance), renal plasma flow [RPF; para-aminohippurate (PAH) clearance], microalbuminuria, sodium excretion, proximal sodium tubular reabsorption (lithium clearance), and acid uric metabolism were measured. After 1-month losartan treatment, systolic and diastolic BP (SBP, DBP) decreased significantly throughout the 210-min recording whereas heart rate (HR) was unchanged. GFR (100 +/- 19 vs. 96 +/- 17 ml/min/1.73 m2) and RPF (471 +/- 118 vs. 468 +/- 108 ml/ min/1.73 m2) were not altered by losartan. Rather than occurrence of any modification in filtration fraction (FF), a significant decrease in microalbuminuria was evident (57 +/- 77 vs. 40 +/- 59 mg/24 h, p < 0.05). Urinary sodium excretion was not modified, but an almost significant (p = 0.07) decrease in proximal sodium reabsorption was observed (72.9 +/- 7.7 vs. 68.1 +/- 6.4% of filtered sodium). The increase in renal uric clearance accounted for the significant decrease in serum uric acid (195 +/- 49 vs. 183 +/- 43 microM; p < 0.05). After 1-month losartan treatment, renal function was well preserved; the decrease in uric acid may be of clinical interest when adjuvent diuretic therapy is required.
J Cardiovasc Pharmacol 1996 Aug
PMID:Effects of losartan on renal function in patients with essential hypertension. 885 82

Microalbuminuria is a predictor of overt diabetic nephropathy and macrovascular disease. Thirty-one diabetic patients with persistent urinary albumin excretion rate (AER) of 20-200 mu g min-1 were randomised to receive indapamide 2.5 mg or captopril 37.5 mg daily for 12 weeks. After a 4-week washout, patients received the alternate agent for 12 weeks. Resting blood pressure (BP), AER, cholesterol, triglycerides, and HbA1c were measured at baseline, after 6 and 12 weeks of each treatment, and after a 4-week washout period following each treatment arm. Results from patients who completed at least one treatment arm were analysed by repeated-measures analysis of variance (ANOVA). AER (median value and interquartile range) decreased significantly from baseline after treatment with indapamide and captopril [60(27-106) vs. 40(14-112) and 33(17-100); p < 0.005], but there was no difference between the effects of the two agents. Mean systolic BP (SBP) was also significantly reduced with treatment, and no difference was noted between the effects of the two agents. No correlation between changes in AER and SBP was noted with either agent. Diastolic blood pressure (DBP), cholesterol, triglycerides, and HbA1c did not change during the study. These results suggest that indapamide is an effective alternative to angiotensin-converting enzyme (ACE) inhibitors in the treatment of diabetic patients with microalbuminuria.
J Cardiovasc Pharmacol 1996 Mar
PMID:Indapamide is as effective as captopril in the control of microalbuminuria in diabetes. 890 5

This paper reviews the effects of antihypertensive drugs on various aspects of renal function such as renal hemodynamics, sodium excretion and microalbuminuria. The discussion also includes the renin-angiotensin system. It is concluded that most agents reduce renal vascular resistance, at least in patients who respond with a drop in blood pressure. Microalbuminuria usually also falls, although this effect may be variable. Changes in renin and sodium excretion depend upon the type of drug used. With the present state of knowledge, it is not possible to define which type of treatment is most beneficial for the kidney in the long term.
Cardiovasc Drugs Ther 1997 Jan
PMID:Effects of antihypertensive drugs on various aspects of renal function. 911 Jan 25

In summary, carvedilol lowers blood pressure effectively. There is a decrease in left ventricular mass. Carvedilol has a good metabolic profile and seems to improve insulin sensitivity. Through its effects on the endothelial function and its antioxidative properties carvedilol has positive effects on the atherosclerotic process. Carvedilol also decreases microalbuminuria. In several aspects carvedilol differs from the conventional beta-blocking drugs, and some of these effects are now being investigated in new studies.
Scand Cardiovasc J Suppl 1998
PMID:Betablockers: old concept in a modern approach. 954 Jan 34

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.
J Cardiovasc Pharmacol 1998
PMID:Relationships among diabetes, microalbuminuria, and ACE inhibition. 973 36


1 2 3 4 5 6 Next >>