Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 'discovery' of losartan represents three separate discoveries: (1) losartan as the unique biphenyltetrazole molecule and the first of a new chemical class; (2) losartan as a tool to identify AT1-subtype receptors; and (3) losartan as a specific probe for exploring the multiple roles of angiotensin II (Ang II) in normal physiology and pathologic states. Losartan is the first nonpeptide orally active Ang II receptor antagonist to reach clinical trials. Losartan was selected for its affinity for Ang II receptors, functional antagonism of Ang II, lack of agonist properties, and oral anti-hypertensive effects. Losartan has been widely used to define the distribution and function of AT receptor subtypes. Although possible roles of the AT2 subtype have been reported, virtually all of the known effects of Ang II are blocked by losartan. Specific AT1 receptor blockade has been broadly compared with ACE inhibition. Possible differences on the basis of AT1 selectivity, bradykinin potentiating effects and Ang II formed by non-ACE pathways are discussed. Losartan blocks the vascular constrictor effect of Ang II, the Ang II-induced aldosterone synthesis and/or release, and the Ang II-induced cardiovascular 'growth' in vitro and in vivo. In various models of experimental hypertension, losartan prevents or reverses the elevated blood pressure and the associated cardiovascular hypertrophy similar to ACE inhibitors. Likewise, in models of renal failure (for example reduced renal mass, puromycin, ochratoxin), losartan, like ACE inhibition, markedly reduced the elevation in blood pressure, proteinuria or sclerosis. In aortocaval shunt, coronary ligation and ventricular pacing models of heart failure, losartan demonstrated a pathological role for Ang II by reversing the associated haemodynamic findings. In SHR-stroke prone, losartan dramatically increased survival while having a limited effect on blood pressure, suggesting a non-pressure dependent effect of Ang II. These collective data show that Ang II exerts complex pathological effects in experimental models of vascular, cardiac, renal and cerebral disease. The effectiveness of losartan in experimental models of heart failure supports its evaluation in clinical trials with patients with heart failure.
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PMID:Discovery of losartan, the first angiotensin II receptor antagonist. 858 79

Recent studies indicated that polymorphonuclear leukocytes (PMNL) were primed to produce superoxide (O2-) in various types of glomerulonephritis with a particular importance in IgA nephropathy (IgAN). In this study, we have examined O2- production and receptor expression for the Fc portion of IgA (Fc alpha R) in monocytes to evaluate their incorporation in IgAN, since infiltration of these cells in the glomeruli are more commonly observed than that of PMNL. Similar to PMNL, monocytes obtained from IgA nephropathy (IgAN) seemed to be primed both non-specifically and specifically, as increased O2- generation was observed to N-formyl methionyl leucyl phenylalanine (FMLP) and phorbol myristate acetate (PMA), as well as IgA aggregates stimulants, respectively. Monocytes O2- generation to IgA aggregates was comparatively higher in amount than in PMNL, and showed a correlation with the severity of proteinuria in IgAN patients. Flow cytometric assessment showed an increased expression of Fc alpha R on circulating monocytes in IgAN patients which showed a linear correlation with the amount of IgA-induced O2- generation. Comparing with the previous literature on PMNL, inflammation-related substances such as cytokines/immune complexes, particularly IgA immune complexes which present in the circulation of IgAN, can prime the phagocytic cells in the circulation for a burst of O2- generation to a second stimulus. The increased expression of Fc alpha R appears to be associated with the increase in priming and the degree of priming can be reflected in the severity of proteinuria/hematuria, although it can not be defined as a cause or consequence of this disease.
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PMID:Monocyte superoxide generation and its IgA-receptor in IgA nephropathy. 861 50

Whether ACE inhibitors (ACEi) differ from other antihypertensives in their efficacy to lower proteinuria is controversial. We therefore performed a meta-analysis of articles on this subject. The secondary objective in our meta-analysis was to study whether there is any difference between diabetic and non-diabetic patients in antiproteinuric response to blood pressure reduction. To identify all articles we performed a computer search using the bibliographic databases. To minimize publication bias, only trials in which a direct comparison was made between an ACEi and another antihypertensive were included. Studies performed both in diabetic and in non-diabetic patients were eligible. Included were 41 studies, comprising 1124 patients, of which 558 had non-diabetic renal disease. The mean antiproteinuric effect of ACEi was significantly greater than that of their comparator drugs: -39.9% (95% confidence interval: -42.8 to 36.8%) versus -17.0% (-19.0 to -15.1%) respectively (difference 24% (19.5 to 28.6%)). The blood-pressure-lowering effect was equal: -12.0% (-12.8 to -11.2%) versus -11.4% (-11.7 to -11.1%) respectively (difference -0.8% (-1.8 to 0.2%)). Thus it may be concluded that ACEIs confer an antiproteinuric effect beyond that attributable to their blood-pressure-lowering effect. A wide interstudy variation in antiproteinuric response to non-ACEI antihypertensives was observed. Multiple variable regression analysis was performed to assess which factors may explain this heterogeneity. From the comparator drugs, the class was of no importance: calcium-channel antagonists (CCA), beta-blockers, and a rest group of other drug types showed a similar response. Patient characteristics such as initial GFR and blood pressure partly explained the variation in response, but most of it appeared dependent on the blood pressure reduction achieved. Furthermore the type of CCA is of importance, with nifedipine having the least effect. A significantly greater antiproteinuric effect of 'non-ACEI' antihypertensives was found in diabetic patients compared to non-diabetics. However, this coincided with a greater blood pressure reduction in diabetics. Adjusted for differences in blood pressure control, diabetics showed even a slightly lesser antiproteinuric response to non-ACEI antihypertensive compared to non-diabetics.
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PMID:Antiproteinuric effect of blood-pressure-lowering agents: a meta-analysis of comparative trials. 864 49

Diabetic nephropathy is the leading cause of uremia in Italy and other industrialized countries: once diabetic nephropathy commences, it advances slowly but inexorably to uremia. Prevention begins with strict control of blood sugar to inhibit or normalize glomerular hyperfiltration, and control of blood pressure to prevent glomerular hypertension and decrease microalbuminuria. Pharmacological measures include ACE-inhibitors and calcium channel blockers, alone or in combination, to reduce proteinuria and preserve renal function. It is believed that some classes of anti-hypertensive drugs have a direct pharmacological depressive effect on cell growth factors that lead to mesangial sclerosis: ACE-inhibitors would thus depress angiotensin II, and the calcium channel blockers would inhibit the increase in intracellular calcium of the mesangial cells which increases gene expression of early growth. Dietary sodium restriction seems to correct the expansion of the sodium pool and related volemic expansion hypertension. A protein-poor diet limits the precapillary glomerular vasodilatation resulting from protein-induced hyperaminoacidemia. The earlier dietetic and pharmacological measures are taken, the more effective they become: while they cannot arrest diabetic nephropathy once it has commenced, they are able to delay evolution of the disease to uremia.
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PMID:[The feasibility and current limits in the prevention of diabetic nephropathy]. 864 29

The pathogenesis of steroid-sensitive nephrotic syndrome (SSNS) is poorly defined. We previously demonstrated that monocytes from SSNS patients with proteinuria were activated to display exaggerated phagocytosis of opsonized particles and paradoxically reduced chemotaxis. In this study, we evaluated the capacity of hydrogen peroxide (H2O2) release from monocytes in 19 patients with SSNS and 13 healthy controls, by exposure to phorbol myristate acetate (PMA), using scopoletin method. Of 19 patients of SSNS, 7 were proteinuric and 12 in remission. The H2O2 release was significantly higher in SSNS patients with proteinuria than those in remission or normal controls [177.49 +/- 94.75 (mean +/- S.D.) vs. 60.67 +/- 58.89 (p < 0.02) or 85.02 +/- 48.62 nmol/90 min/mg cell protein (p < 0.05)]. Follow-up measurements in two SSNS patients showed that H2O2 release was reduced when proteinuric condition was improved to be in remission. Our data suggest that monocytes in SSNS with proteinuria were activated and were prepared to receive some extracellular signaling leading to protein kinase-C activation for releasing H2O2.
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PMID:Capacity of H2O2 release from monocytes in steroid-sensitive nephrotic syndrome. 872 9

Hypertension is both an exacerbating factor for, and a consequence of, diabetic renal disease. In diabetic patients, hypertension is associated with increased total body sodium secondary to impaired renal excretion, and increased vascular reactivity, notably to catecholamines and angiotensin II. The mechanisms causing these changes are discussed. Control of hypertension will slow the progression of diabetic renal disease and the inexorable decline in GFR. A number of studies now suggest that in proteinuric IDDM and NIDDM patients angiotensin converting enzyme inhibitors (ACE-I) may have additional reno-protective effects in addition to their hypotensive action. In addition ACE-I will reduce proteinuria and delay the onset of diabetic nephropathy in normotensive microalbuminuric IDDM and NIDDM patients. Use of ambulatory blood pressure monitoring indicates that such patients may not be truly 'normotensive'. On-going studies seem to suggest that the most reno-protective blood pressure is the lowest one achievable, as long as the patient remains asymptomatic. Further studies are required to assess the impact of blood pressure control, and especially ACE-I, on the incidence of end-stage renal failure. In addition, more direct comparisons between different pharmacological agents in early diabetic renal disease would be useful.
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PMID:The management of hypertension in diabetes: with special reference to diabetic kidney disease. 873 20

Microalbuminuria (MA) is a term used for urinary albumin excretion between 20 and 200 micrograms/min. or 30-300 mg/24 h. This definition is not used by all authors. In addition, various methods may influence the results. The significance of MA concerns the prognosis in diabetics. For the juvenile type 1 diabetes nephropathy is the most important complication. In adult type 2 diabetics the prognosis concerns mainly cardiovascular death. The excess mortality to be attributed to MA is several fold in type 1 diabetes, less in the adult onset type variety. MA is the expression of an incipient general disease of blood vessels touching as much the kidney as the heart. According to the presence or absence of other vascular damage. MA develops toward nephropathy or cardiovascular complications. The features leading to or worsening MA are elevated blood pressure, poor glucose control, elevated lipoproteins, diminished insulin sensitivity and probably smoking. Retinopathy is an indicator for particularly sensitive patients responding with the development of MA upon only mildly elevated blood pressure or poor metabolic control. The prevalence of MA is close to 20% for both types of diabetes. Non-diabetic persons under 60 years of age exhibit MA in 2-10%, the elderly in 20-30%. For non-diabetic persons with hypertension MA is reported to be present in 19%. Over a time span of 5 years, 19% of type 1 patients with MA develop proteinuria of more than 300 mg/24 hours. In a third of cases albumin excretion normalises. In the remaining half a small progression of MA occurs. For type 2 patients the increased mortality risk is restricted to the first 5 years, thereafter the survival curves return to those of patients without MA. In these patients the excess mortality is already present at albumin excretion rates above 10 micrograms/min. Higher values have, therefore, to be considered pathological. For the treatment of the syndrome ACE-inhibitors and ev. Ca-antagonists (with the exception of dihydropyridine, nifedipine) are recommended. They reduce albumin excretion by 50%. In a single study (yet) with type 1 diabetes mortality also was reduced by 40-50%. This would imply that the excess mortality could be halved in patients undergoing this treatment.
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PMID:[Microalbuminuria in diabetes mellitus--illness or symptom?]. 873 41

The kidneys play an important role in the development of cardiovascular risk factors. It is well known that heavy proteinuria can induce hyperlipidemia, the uric acid is elevated in some renal deficiencies and that hypertension develops in most end stage renal diseases. In prehypertensive states, specially in subjects with a family history of hypertension, some hemodynamic changes take place, characterized by an increase in renal vasoconstriction with a reduction in renal plasma flow and an elevation of sodium reabsorption. The mechanisms for these alterations are not well understood, but an increase in intracytosolic calcium in vascular smooth muscle cells, a reduction in vasodilatory substances such as nitric oxide and an increased sympathetic nervous activity have been proposed. In normotensive subjects with two hypertensive parents a reduction in sodium diet, an increase in protein intake or in arginine diet could prevent established essential hypertension from developing. In borderline hypertension an early therapy with low doses of calcium antagonists, ACE inhibition or diuretics could be indicated.
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PMID:Can the kidney prevent cardiovascular diseases? 874 38

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

Hypertension is a common finding in patients with renal parenchymatous diseases. Development of hypertension causes increased proteinuria, decline in glomerular filtration rate and reduced life span in experimental models of glomerulonephritis. Hypertension has been shown to reduce glomerular filtration rate in man. It is therefore important to treat hypertension. The blood pressure should be reduced to about 140/80 mm Hg. Reduction of glomerular capillary pressure, inhibition of glomerular permeability, renal hypertrophy and inhibition of mesangial metabolism are the main mechanisms of renal protection during antihypertensive therapy. Autoregulation of the renal blood flow probably has an impact on these mechanisms. Impaired autoregulation is found in kidneys with low glomerular filtration rate and during treatment with calcium channel blockers. Alpha receptor blockers, angiotensin converting enzyme inhibitors (ACE-) and angiotensin II receptor blockers do not interfere with autoregulation. All types of antihypertensive drugs provide similar renal protection when the glomerular filtration rate is reduced. When calcium channel blockers are used in kidneys with normal or slightly reduced function, either blood pressure should be kept strictly at normal levels or these type of drugs should be combined with ACE inhibitors or angiotensin II receptor blockers.
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PMID:[Treatment of hypertension in renal parenchymal diseases]. 876 45


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