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)

Angiotensin-(1-7) (Ang-[1-7]) is a bioactive component of the renin-angiotensin system, which has depressor, vasodilatory, and antihypertensive actions. In normal pregnancy, we questioned whether the known rise in plasma angiotensin II (Ang II) is counterbalanced by an increase in plasma Ang-(1-7) and whether Ang-(1-7) levels are decreased in preeclampsia and may thus be a factor involved in the development of hypertension. Nulliparous preeclamptic subjects, third-trimester normotensive pregnant subjects, and a nonpregnant group were enrolled (n = 15/group). Preeclamptic subjects had no previous history of hypertension or renal, connective-tissue, or metabolic disease, but at the time of delivery had significant hypertension (159 +/- 3/98 +/- 3 mmHg) and > or = 3+ proteinuria. Plasma Ang-(1-7) was increased by 51% in normal pregnancy (p < 0.05). Plasma Ang I, Ang II, and renin activity were also significantly elevated in normal pregnancy. In preeclamptic subjects, Ang-(1-7) was significantly decreased (p < 0.01) compared with normal pregnant subjects. All other components of the renin-angiotensin-aldosterone system, except serum angiotensin-converting enzyme, were reduced in preeclamptic subjects compared with normal pregnant subjects; only plasma Ang II remained elevated in preeclamptic compared with nonpregnant subjects. These studies demonstrate, for the first time, increased plasma Ang-(1-7) in normal pregnant subjects compared with nonpregnant subjects and decreased Ang-(1-7) in preeclamptic subjects compared with normal pregnant subjects. In preeclampsia the decreased plasma Ang-(1-7) in the presence of elevated Ang II is consistent with the development of hypertension.
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PMID:Angiotensin-(1-7) in normal and preeclamptic pregnancy. 1245 Mar 15

In the past few years diabetes has become the leading cause of end-stage renal disease in all Western countries. A correlation between blood pressure and rate of progression in diabetic nephropathy was noted very early, and increased local activity of the renin angiotensin system was identified as a major pathophysiological mechanism for proteinuria and nephrosclerosis in diabetic patients. Angiotensin converting enzyme (ACE) inhibitors have been shown to slow progression of nephropathy in type 1 diabetic patients. The majority of diabetic patients with nephropathy, however, are suffering from type 2 diabetes and until last year there was no convincing evidence of ACE inhibitors being able to slow progression in type 2 diabetic patients with nephropathy. Three new studies now fill this gap, showing that angiotensin receptor blockers (ARB) are nephroprotective in patients with type 2 diabetes, independently of blood pressure. This review provides an in-depth discussion of the results of these studies and provides recommendations for patient management.
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PMID:Angiotensin receptor antagonists in patients with nephropathy due to type 2 diabetes. 1255 90

Losartan is an orally active, selective, nonpeptide, angiotensin II AT(1) receptor antagonist. Losartan 50 or 100 mg/day was significantly more effective than placebo in reducing the incidence of a doubling of serum creatinine, end-stage renal disease (ESRD) or death (43.5% vs 47.1%, p = 0.02) in a pivotal, well designed trial (Reduction of Endpoints in Non insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan [RENAAL] study) in 1513 patients with type 2 diabetes mellitus and proteinuria. Losartan also significantly reduced the incidence of doubling of serum creatinine level (p = 0.006), ESRD (p = 0.002), ESRD or death (p = 0.01) and doubling of serum creatinine and ESRD (p = 0.01) compared with placebo in the RENAAL trial. There were similar incidences of overall mortality and morbidity and mortality from cardiovascular causes between treatment groups. In addition, data from several nonblind and double-blind studies indicates that losartan effectively reduces the mean albumin excretion rate. Two double-blind studies show that losartan has similar effects to enalapril on kidney function. Data from 4058 patients (3300 with essential hypertension) who have received losartan (10-150 mg/day) in clinical trials indicate it is well tolerated. In the RENAAL study 17.2% and 21.7% of losartan and placebo recipients discontinued treatment because of adverse events, but causality was not determined.
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PMID:Losartan in diabetic nephropathy. 1255 62

Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II (Ang II), AT(1)-receptor blockers (ARB) is the cornerstone of renoprotective therapy. Still, the number of patients with end-stage renal disease is increasing worldwide, prompting the search for improved renoprotective strategies. In spite of proven efficacy at group level, the long-term renoprotective effect of RAAS blockade displays a marked between-patient heterogeneity, which is closely linked to between-patient differences in the intermediate parameters of blood pressure, proteinuria and renal haemodynamics. Of note, the between-patient differences by far exceed the between-regimen differences, and thus may provide a novel target for exploration and intervention. The responsiveness to RAAS blockade appears to be an individual characteristic as demonstrated by studies applying a rotation-schedule design. The type and severity of renal disease, obesity, insulin-resistance, glycaemic control, and genetic factors may all be involved in individual differences in responsiveness, as well as dietary factors, such as dietary sodium and protein intake. Several strategies, such as dietary sodium restriction and diuretic therapy, dose-titration for proteinuria, and dual RAAS blockade with ACE-I and ARB, can improve the response to therapy at a group level. However, when analysed for their effect in individuals, it appears that these measures do not allow poor responders to catch up with the good responders, i.e. in spite of their efficacy at group level, the available measures are usually not sufficient to overcome individual resistance to RAAS blockade. We conclude that between-patient differences in responsiveness to renoprotective intervention should get specific attention as a target for intervention. Unravelling of the underlying mechanisms may allow development of specific intervention. Based on the currently available data, we propose that response-based treatment schedules, with a multidrug approach titrated and adapted at individual responses rather than fixed treatment schedules, may provide a fruitful strategy for more effective renoprotection.
J Renin Angiotensin Aldosterone Syst 2002 Dec
PMID:Between-patient differences in the renal response to renin-angiotensin system intervention: clue to optimising renoprotective therapy? 1258 64

Angiotensin converting enzyme (ACE) inhibitors preserve native kidney function in patients with renal disease better than other antihypertensive drugs, most likely because they more effectively reduce proteinuria. The plasma concentration of the ACE inhibitors target is, at least in part, under genetic control. A polymorphism of the ACE gene based on the presence or absence of a 287 base pair element in intron 16 accounts for 47% of the total phenotypic variance in the plasma ACE levels of healthy individuals. Unfortunately, pharmacogenetic studies performed so far do not provide a clear answer as to whether the efficacy of the reduction of proteinuria by ACE inhibitors is influenced by the ACE genotype - probably because these studies were not primarily designed to answer this question. This paper will try to outline some aspects that should be considered before an appropriate study on this topic is initiated.
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PMID:Pharmacogenomics of angiotensin converting enzyme inhibitors in renal disease--pathophysiological considerations. 1260 49

Risk factors for progression of kidney disease include hypertension, proteinuria, male sex, obesity, diabetes mellitus, hyperlipidemia, smoking, high-protein diets, phosphate retention, and metabolic acidosis. Angiotensin II production upregulates the expression of transforming growth factor-beta1, tumor necrosis factor-alpha, nuclear factor-kappaB, and several adhesion molecules and chemoattractants. In addition to angiotensin, other vasoactive compounds, such as thromboxane A(2), endothelin, and prostaglandins, are upregulated. Treatment with one of several growth factors may ameliorate the progression of kidney disease: insulin-like growth factor-1, hepatocyte growth factor, and bone morphogenetic protein-7.
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PMID:Progression of chronic renal disease. 1261 42

Angiotensin II (ANG II) is intimately involved in normal renal function, and is estimated to exist at a normal physiological range of 6-10 nM within the renal tubules. The potential role that intrarenal ANG II may play in renal disease was assessed by perfusing isolated rat kidneys with or without excess intratubular levels of ANG II, which may mimic changes in the intrarenal RAS under pathological conditions. The effects of increased systemic ANG II were also determined by infusing rats with ANG II by osmotic pump. In isolated perfused kidneys, ANG II significantly and specifically increased the fractional clearance of albumin to clinical levels, as determined by using radiolabelled albumin. This effect was reversible, as removing ANG II from the perfusate caused the albumin fractional clearance to decrease to pre-ANG II exposure levels. The increase in fractional clearance of albumin was not correlated with renal hemodynamic changes, nor glomerular permeability alterations as measured by the fractional clearance of 36 A Ficoll and immunoglobulin G. Immunochemical analysis using anti-alpha-tubulin antibody of perfused kidney sections revealed that ANG II caused a marked disruption of tubular epithelial cytoskeletal components, through disassembly and reorganization of alpha-tubulin. This disruption was reversible. In vivo, osmotic pump delivery of ANG II at less potent dosage caused a proteinuria (Biuret) and an albuminuria (radioimmunoassay) in rats, from as early as 2 days after pump implantation. These results demonstrate that ANG II may reversibly induce clinical levels of albuminuria. These data point to an important role for renal tubules and the intratubular lumen concentrations of ANG II in the renal processing of albumin.
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PMID:Reversible angiotensin II-mediated albuminuria in rat kidneys is dynamically associated with cytoskeletal organization. 1262 71

Human immunoglobulin A is represented by two structurally and functionally distinct subclasses: IgA1 and IgA2. IgA1, which is almost exclusively present in the mesangial deposits in IgA nephropathy patients, contains in its hinge region three to five O-lined carbohydrate chains. A fraction of IgA1 molecules in the circulation of IgA nephropathy patients exhibits aberrant glycosylation. As a result of changes in glycosylation, the neoepitopes represented by glycans are exposed and recognized by naturally occurring antibodies with antiglycan specifciities, and immune complexes are generated. The deposits of these immune complexes in the glomerular mesangia elicit inflammatory response known as IgA nephropathy. Epidemiological studies have shown that dominant hematuria, either isolated or combined with mild proteinuria, is the most frequent urinary syndrome in glomerulonephritis. The morphologic finding of this syndrome is most frequently IgA nephropathy. Originally considered a benign disease, IgA nephropathy is now recognized as a frequent cause of chronic renal failure. The progression is signalized by increasing proteinuria and hypertension. Therefore, a control of blood pressure and lowering of proteinuria remain the corner-stones of the treatment. Angiotensin converting enzyme inhibitors and AT1 blockers may lower both blood pressure and proteinuria and are now increasingly promoted even for treatment of normotensive patients. Steroids are administered to patients with severe proteinuria. High-doses of fish oil seem to slow down the rate of renal failure.
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PMID:[IgA nephropathy. Significance of immunoglobulin A glycosylation in pathogenesis and clinical presentation]. 1265 29

Renin-angiotensin system (RAS) overactivity has been implied in progressive renal function loss. We investigated whether changes in the renal expression of RAS components are specifically associated with the proteinuric kidney. Unilateral adriamycin-induced proteinuria was obtained by clamping the left renal artery before injection of adriamycin. In control animals, both left and right renal arteries were clamped. Twelve weeks later, mRNA expression of RAS components was determined in both kidneys. In the affected and non-affected kidney of the unilateral proteinuric rat, we demonstrate up-regulation of angiotensin- converting enzyme (ACE) mRNA (213%+22 and 188%+24 of controls, respectively), up-regulation of transforming growth factor beta (TGF-beta) mRNA (956%+229 and 418%+56) and down-regulation of angiotensin type 2 receptor (AT2-R) mRNA (24%+5 and 20%+5). The expression of angiotensin type 1 receptor (AT1-R) mRNA and inositol 1,4,5- trisphosphate receptor type I (IP3R-I) mRNA were unchanged. In conclusion, renal expression of ACE, AT2-R, and AT1-R mRNA is not mediated by protein leakage. Local intrarenal protein leakage did influence renal TGF-beta mRNA expression.
J Renin Angiotensin Aldosterone Syst 2003 Mar
PMID:Role of proteinuria in the regulation of renal renin-angiotensin system components in unilateral proteinuric rats. 1269 52

Prevalence of diabetic nephropathy is increasing. Understanding of pathogenesis and clinical picture helps to manage this disease. Recent data of the research of this disease support that the renin-angiotensin system plays a pivotal role in the pathogenesis. Hyperglycaemia activates the renin-angiotensin system and induces transforming growth factor-beta expression. These both lead to glomerulosclerosis and tubulointerstitial fibrosis. Diabetic nephropathy develops earlier and progress faster in patients with DD or ID genotypes of angiotensin-I-converting-enzyme gene. Angiotensinogen and type 1 angiotensin-II-receptor gene mutations may be also predisposing factors for diabetic nephropathy. All these factors can be responsible for the hyperfiltration, albuminuria, salt sensitivity, and hypertension, which are characteristic features of diabetic nephropathy. According to these, one can suppose that inhibitors of the renin-angiotensin system are effective in the prevention and treatment of this disease. Evidence of clinical studies suggests that angiotensin-I-converting-enzyme inhibitors in type 1 diabetes can prevent overt nephropathy, decrease proteinuria, inhibit the loss of the glomerular filtration and decelerate progression. Angiotensin-II-receptor blockers exert the same effect in type 2 diabetic patients, and presumably angiotensin-I-converting-enzyme inhibitors have similar activity in this group of patients. That is why, in the case of intolerance of one class of drugs, the other should be substituted. Combination therapy of angiotensin-I-converting-enzyme inhibitors with angiotensin-II-receptor blockers can be the choice of treatment in the future.
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PMID:[Role of the renin-angiotensin system in the pathogenesis, clinical picture and treatment of diabetic nephropathy]. 1272 86


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