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)

Nephrotoxic nephritis (NTN) is characterized by an influx of leukocytes into the glomerulus, with accompanying glomerular dysfunction and a marked increase in glomerular eicosanoid production. We examined the relationship between the glomerular inflammatory cell infiltrate and the concomitant metabolic/functional changes in this model of renal disease using a combination of in vivo immunologic strategies to both decrease [X-irradiation and cobra venom factor (CVF)] and increase (preimmunization with rabbit immunoglobulin G or accelerated NTN) the inflammatory cell infiltrate. With the use of these manipulations, a close correlation between glomerular leukocytes and the proteinuria of NTN was observed. The ablative strategies (X-irradiation and CVF) also attenuated the increase in leukotriene B4 (LTB4) generation seen with NTN and virtually completely prevented the increase in thromboxane B2 (TxB2) production (basal and angiotensin II elicited). Accelerated NTN, in contrast, increased and prolonged the rise in glomerular LTB4 production and exacerbated the increase in TxB2 production. Glomerular prostaglandin E2 production was not altered by the induction of nephritis nor any of the aforementioned immunologic manipulations. Regression analysis established that glomerular TxB2 production correlated significantly with the leukocyte influx at both 3 and 24 h. Glomerular LTB4 production correlated only with the presence of leukocytes at 3 h. Both glomerular TxB2 and LTB4 production were closely correlated with the renal dysfunction as assessed by proteinuria. These data suggest that leukocytes play a direct critical role in both the functional and metabolic alterations that occur in the setting of NTN. They further imply that leukocytes are crucial to the observed increase in glomerular eicosanoid production.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of leukocytes in metabolic and functional derangements of experimental glomerulonephritis. 187 46

Nonsteroidal anti-inflammatory drugs, especially indomethacin, have variable effects on proteinuria when used alone, but can dramatically reduce proteinuria if combined with diuretics and sodium restriction. Reduction of angiotensin II concentrations in plasma and kidney following angiotensin-converting enzyme inhibition also reduces proteinuria, not only in nephrotic conditions but also in diverse diseases, including diabetes mellitus, glomerulosclerosis following subtotal nephrectomy, and membranous nephropathy. The reduction of proteinuria appears independent of decrements in blood pressure since other hypotensive agents do not alter proteinuria in these conditions.
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PMID:Prostaglandins, angiotension II, and proteinuria. 211 84

This study was designed to contrast the effects of prolonged treatment with a thromboxane (Tx) synthase inhibitor (UK 38485 or SC 41156) and a Tx receptor antagonist (SQ 29548) on the development of angiotensin II (Ang II)-salt-induced hypertension. Ang II infusion (125 ng/min i.p. for 12 days) in rats drinking 0.15 M NaCl resulted in severe hypertension accompanied by proteinuria, reduction of urinary creatinine excretion and augmentation of urinary TxB2 excretion and TxB2 release from aortic rings and renal cortex slices. In saline-drinking rats undergoing Ang II infusion, the concomitant administration by gavage of UK 38485 (100 mg/kg/day) or SC 41156 (25 mg/kg/day) reduced serum and urinary TxB2 and TxB2 release from aortic rings and/or renal cortex slices, but it was without effect on the development of hypertension. In contrast, concomitant infusion of SQ 29548 (4.2 mg/24 hr s.c.) significantly attenuated the increase of blood pressure produced by the infusion of Ang II in saline-drinking rats. This effect of SQ 29548 may be the consequence of blockade of the actions of one or more endogenous eicosanoids that increase blood pressure by a mechanism(s) involving interaction with TxA2 receptors. This implies that pressor eicosanoids play a contributory role in the development of severe Ang II-salt hypertension.
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PMID:Contrasting effect of thromboxane synthase inhibitors and a thromboxane receptor antagonist on the development of angiotensin II-salt-induced hypertension in rats. 213 70

The existence of tissue renin angiotensin system (RAS) has been widely suggested in the recent literature by 2 main approaches: first, a dissociation between antihypertensive effects of angiotensin converting enzyme (ACE) inhibitors and the levels of stimulation of the circulating RAS; secondly, by the demonstration of the presence of the 3 key-proteins of the system (angiotensinogen, creatinine, and converting enzyme) within the 3 main target-organs of hypertension (i.e. kidney, heart and vessels). Those organs are capable to synthetize locally angiotensin II. Ramipril, a new ACE inhibitor (Triatec), which possesses a high affinity for tissue CE of those organs, according to previous publications by Unger, has been used as a tool for the investigations of the inhibition of those systems in human hypertension: a decrease of micro proteinuria has been without antihypertensive effects. In binephrectomized patients, ramipril has been shown to possess an antihypertensive effect. Finally, an important improvement of myocardial hypertrophy has been shown in hypertensive patients. Furthermore, this effect has been observed in animals (rats with aortic stenosis) even with low doses without antihypertensive effects. Further studies with new methodological approaches are still necessary.
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PMID:[Tissue renin-angiotensin system. Physiology and physiopathological value of their inhibition by ramipril]. 214 94

Converting enzyme inhibitors (CEIs) are widely used in treatment of essential hypertension. Large-scale clinical studies have shown that CEIs are well tolerated and cause fewer side effects than most other antihypertensive agents. The latter observation is fundamental for compliance with long-term treatment. There do exist, however, some side effects which although rare are not negligible. It is necessary though to distinguish between side effects linked to the class of therapeutic agents and those associated with particular structural features. Three types of side effects have been seen: 1) manifestations linked to inhibition of angiotensin II with systemic vasodilation (hypotension, vertigo) and decreased glomerular pressure (functional renal impairment) with preferred onset in renovascular hypertension; 2) potentiation of the bradykinin-prostaglandin system which causes cutaneous eruptions and for reasons still poorly understood a cough which may justify discontinuance of treatment: 3) side effects for which the sulfydryl group is essentially responsible (rash, dysgeusia, neutropenia, proteinuria) and which basically appear to be linked to the use of high doses of captopril. In general terms, and bearing in mind the frequently dose-dependent character of the side effects, it is advisable to prescribe low doses of CEIs, and this therapeutic approach is strengthened by the possibility of concomitant use of a thiazide diuretic allowing improved antihypertensive effects, coupled to better reciprocal tolerance of the drugs. The end result is a better quality of life for the hypertensive subject, and hence improved compliance with long-term treatment.
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PMID:[Quality of life of patients with hypertension treated with converting enzyme inhibitors]. 218 15

Angiotensin (Ang) II and prostaglandins, especially prostaglandins E2 and I2, regulate the glomerular filtration of albumin. Albuminuria can be induced by angiotensin II and possibly by prostaglandins. Angiotensin converting enzyme inhibition with captopril, enalapril or lisinopril reduces albuminuria and glomerular injury in experimental and clinical renal diseases, especially diabetes mellitus. Inhibition of prostaglandin synthesis with non-steroidal anti-inflammatory drugs reduces albuminuria in nephrotic patients regardless of the aetiology of the nephrosis. Judicious clinical use of either class of therapy can result in sustained reductions (50-75%) in proteinuria and possible attenuation of the rate of decline of glomerular function.
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PMID:The roles of angiotensin II and prostaglandins in the regulation of the glomerular filtration of albumin. 218 53

The effects of angiotensin-converting enzyme (ACE) inhibitors on renal hemodynamics vary widely depending on the preexisting physiologic and pathologic state of the kidneys. Although some studies of ACE inhibitors in primary essential hypertension have demonstrated increases in glomerular filtration rate (GFR) and effective renal plasma flow in patients with renal impairment, other studies have not shown these same beneficial results. The difference may involve the choice of ACE inhibitor used in the investigations, but controlled comparison trials are needed to determine whether this is the case. The use of ACE inhibitors in renovascular hypertension remains controversial. ACE inhibition can interfere with the autoregulation of GFR mediated by angiotensin II and may lead to deterioration of renal function, especially in patients with bilateral renal artery stenosis or stenosis of a solitary kidney. Additionally, ACE inhibitors have been shown to cause a decline in GFR in the kidney affected by the stenosis, whether or not clinically apparent renal insufficiency occurs. Although the functional impairment associated with ACE inhibitors in renal artery stenosis has generally been reversible following removal of the drug, the consequences of a long-term reduction in GFR are unknown. Treatment of stable congestive heart failure (CHF) with ACE inhibitors can result in enhancement of GFR and reduction of sodium and fluid retention, thus improving the clinical state. However, in patients with decompensated cardiac failure, renal perfusion pressures may already be at or near the autoregulatory breakpoint and ACE inhibition may cause deterioration of renal function. In general, ACE inhibitors can be used safely in CHF if they are initiated cautiously, with adjustment of ACE inhibitor and diuretic dosages to avoid systemic hypotension and sodium and fluid depletion. In studies comparing the agents, enalapril and lisinopril have both been shown to cause higher incidences of renal function deterioration than has captopril. These findings suggest that the more complete or sustained ACE inhibition seen with the longer-acting agents may be detrimental to renal function in patients with CHF. The use of ACE inhibitors in the treatment of proteinuria is the newest area of research with these agents. At present it appears that ACE inhibitors reduce urinary protein excretion the most effectively in diabetic patients with mild proteinuria and in hypertensive patients with renal insufficiency and proteinuria due to glomerular disorders. More study is needed to determine whether these agents can reduce the rate of renal failure progression and to define the patient populations expected to benefit most.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Angiotensin-converting enzyme inhibitors and renal function. 218 38

The purpose of this study was to measure components of the renin angiotensin system in patients with type 1 diabetes mellitus, with and without nephropathy, to study the renal sensitivity to angiotensin II in uncomplicated type 1 diabetes and to investigate the short and long-term renal effects of angiotensin II reduction with angiotensin converting enzyme inhibitors in patients with diabetic nephropathy. In patients with type 1 diabetes without complications, plasma renin activity, angiotensin II and aldosterone levels were normal. In patients with diabetic nephropathy, renin levels were elevated, probably partly as a result of diuretic treatment. However, renin levels were also elevated compared to patients with other renal diseases who had similar treatment and degree of azotemia. The renal sensitivity to angiotensin II was normal in patients with uncomplicated diabetes. The reduction in glomerular filtration rate and renal plasma flow and increases in filtration fraction during A II infusion were equal to those in healthy controls. Nine days' captopril treatment in 15 patients with diabetic nephropathy induced an increase in renal plasma flow and a decrease in filtration fraction. The glomerular filtration rate remained unchanged. During 8 weeks' randomised enalapril or metoprolol treatment in 40 patients with diabetic nephropathy, enalapril treatment reduced proteinuria to half the initial value. Metoprolol treatment had no effect on proteinuria. Furosemide was also used and the dosage was adjusted to give equally effective blood-pressure control in both groups. During long-term treatment with captopril in patients with diabetic nephropathy, the rate of decline in kidney function over time was reduced to one-fourth the initial value even though the blood pressure was only slightly reduced. The renin angiotensin system appears to be functionally intact in diabetes mellitus and interruption by ACE inhibition reduces proteinuria both by blood pressure reduction and by an effect independent of systemic blood pressure. Long-term treatment might protect kidney function in diabetic nephropathy to a greater extent than would be expected from the blood-pressure-lowering effect alone.
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PMID:The renin angiotensin system in diabetes mellitus. A physiological and therapeutic study. 219 80

ACE-inhibitors have many positive features, when treating patients with progressive renal failure. These patients have high mortality in cardiac and vascular complications. It is therefore important to treat hypertension in these patients with drugs which do not have negative effects on lipid-, glucose, or electrolyte-metabolism, and ACE inhibition fulfills these requirements. These drugs decrease left ventricular hypertrophy, which is a positive prognostic sign of hypertensive patients, too. Contrary to regular diuretics, ACE-inhibition does not cause the negative effects associated with activation of the renin-angiotensin system. In many patients ACE-inhibitors decrease proteinuria to a higher degree than other antihypertensive drugs, and this may be an important clinical advantage, particularly in nephrotic patients. ACE inhibition might slow progressive renal failure. This effect may be associated with advantageous intraglomerular hemodynamic changes, but may also associate with inhibition of negative effects of angiotensin II on mesangial hypertrophy and matrix proliferation.
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PMID:[ACE inhibitors' effect on kidney function]. 221 87

Captopril, an angiotensin II-converting enzyme inhibitor, ameliorates the renal mesangial lesions associated with subtotal nephrectomy, a process associated with increased mesangial macromolecular flux and injury. In the present study uninephrectomized rats with proteinuria and focal glomerular sclerosis had increased mesangial heat-aggregated human IgG (AHIgG) uptake. However, uninephrectomized rats treated daily with captopril, which failed to develop either glomerular lesions or proteinuria, also had significantly elevated mesangial AHIgG levels. Our results suggest that increased mesangial macromolecular flux may occur independent of altered glomerular permselectivity changes and proteinuria and appears to be related to glomerular hyperfiltration rather than glomerular hypertension. Further, glomerular mesangial sclerosis may not be the direct result of increased mesangial macromolecular flux.
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PMID:Mesangial macromolecular uptake in captopril-treated uninephrectomized rats. 221 17


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