UMLS:C0033687 - FACTA Search

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 highly atherogenic lipoprotein(a) [Lp(a)] is significantly elevated in patients with renal disease. It is discussed controversially whether Lp(a) concentrations decrease after renal transplantation and whether the mode of immunosuppressive therapy influences the Lp(a) concentrations. In a prospective study the Lp(a) concentrations before and on average 48 months after renal transplantation were measured in 145 patients. The determinants of the relative changes of Lp(a) concentrations were investigated in a multivariate analysis. Patients treated by CAPD showed a larger decrease of Lp(a) than hemodialysis patients, reflecting their markedly higher Lp(a) levels before transplantation. The relative decrease of Lp(a) was higher with increasing Lp(a) concentrations before transplantation in combination with an increasing molecular weight of apolipoprotein(a) [apo(a)]. That means that the relative decrease of Lp(a) is related to the Lp(a) concentration and the apo(a) size polymorphism. With increasing proteinuria and decreasing glomerular filtration rate, the relative decrease of Lp(a) became less pronounced. Neither prednisolone nor cyclosporine (CsA) had a significant impact on the Lp(a) concentration changes. Azathioprine (Aza) was the only immunosuppressive drug which had a dose-dependent influence on the relative decrease of Lp(a) levels. These data clearly demonstrate a decrease of Lp(a) following renal transplantation which is caused by the restoration of kidney function. The relative decrease is influenced by Aza but not by CsA or prednisolone.
Atherosclerosis 1999 Jun
PMID:Lipoprotein(a) plasma concentrations after renal transplantation: a prospective evaluation after 4 years of follow-up. 1040 99

Brain vascular diseases are ranked the third as the cause of morbidity and mortality in majority of the countries of the world. In about 80% of the cases of vascular brain diseases, it is ischemic brain disease (IBD). Atherosclerosis of main cerebral arteries is most frequently responsible for the occurrence and development of IBD. In recent years it was reported for the first time of the association of atherosclerosis and/or its complications and proteinuria. Assuming that there exists the significant association between the degree of proteinuria and clinical parameters of IBD, the aim of this study was to investigate the frequency and patterns of the association of proteinuria and clinical IBD parameters. The study was performed in 180 patients with IBD of atherothrombotic origin and 60 patients with the diseases of non-vascular origin, as the control group. In all patients quantitative determination of proteinuria was performed, and in the patients with IBD was determined the degree of IBD and afterwards the degree of functional and neurologic impairment prior to and at the end of treatment in acute phase using the standardized scales. The results of the study revealed the existence of significant frequency of proteinuria in the patients with IBD, as well as the significant association between the degree of proteinuria and severity of IBD. It was concluded that proteinuria in patients with IBD was probably associated with the atherogenic processes and physiopathologic processes of IBD, respectively, which could have predictive value for the outcome of the disease in the early stage.
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PMID:[Significance of proteinuria in patients with acute ischemic brain disease]. 1043 17

Lecithin: cholesterolacyltransferase (LCAT) transacylates the fatty acid at the sn-2 position of lecithin to the 3beta-OH group of cholesterol forming lysolecithin and the majority of cholesteryl ester found in plasma. LCAT participates in the reverse cholesterol transport pathway in man where it esterifies tissue-derived cholesterol following efflux from peripheral cells into HDL. Only 38 unique mutations in the human LCAT gene have been reported worldwide. Our French female proband presented with corneal opacity and no detectable plasma LCAT activity using either endogenous or exogenous assays. Her total plasma cholesterol and HDL cholesterol were low (2.34 mmol/l and 0.184 mmol/l, respectively) with a very high cholesterol/cholesteryl ester molar ratio (10.9:1). Plasma triglycerides were 0.470 mmol/l with low apo B (40.5 mg/dl), apo A-I (14.7 mg/dl), apo A-II (6.8 mg/dl) and apo E (2.1 mg/dl) levels. Plasma lipoprotein analysis by ultracentrifugation showed very low HDL concentrations and a characteristic shift of the lipoprotein profile towards larger, less dense particles. No proteinuria, renal dysfunction or signs of atherosclerosis were noted at age 45. Sequence analysis of her LCAT gene showed a novel homozygous TG-deletion at residues 138-139 that resulted in a frameshift causing the generation of a stop codon and premature termination of the LCAT protein at amino acid residue 144. Western blotting of the patient's plasma using a polyclonal IgY primary antibody against human LCAT failed to demonstrate the presence of a truncated LCAT protein. A 53 bp mismatched PCR primer was designed to generate an Fsp 1 restriction site in the wild type sequence of exon 4 where the mutation occurred. The 155 bp PCR product from the wild type allele produced a 103 bp and 52 bp fragment with Fsp 1 and no cleavage products with the mutant allele thus permitting rapid screening for this novel mutation.
Atherosclerosis 1999 Sep
PMID:Classical LCAT deficiency resulting from a novel homozygous dinucleotide deletion in exon 4 of the human lecithin: cholesterol acyltransferase gene causing a frameshift and stop codon at residue 144. 1048 97

A decrease of plasma homocysteine (Hcy) may represent a therapeutic promise for reducing the impact of atherosclerosis. N -Acetyl-cysteine (NAC) is a thiol-containing compound interfering with endogenous thiols, cysteine (Cys) and Hcy, by forming with them mixed disulphides with a possibly more efficient renal clearance. The aim of this work was to assess the effect of NAC intravenous infusion on plasma levels of different forms of Hcy and particularly to verify the effect on Hcy renal excretion. We collected basal blood samples at 0.5, 1, 2, 5, 8 and 24 h after the beginning of NAC infusion (50 mg kg(-1)body wt.) and also 24-h urine samples of the day of NAC infusion and of the day before and of the day after the infusion in ten healthy subjects (mean age 73+/-15). Urinary and plasma thiols (Hcy, Cys and NAC) were assayed by HPLC. Both total plasma Hcy (approx. 69%vs basal values) and Cys (approx. 40%vs basal values) fell progressively, reaching a minimum 5 h after infusion start; total free (i.e. not bound to proteins) Hcy (2.2+/-1.8 down from 4.4+/-4.2 nmol ml(-1)) and Cys (70.4+/-39.8 down from 113. 3+/-61.2 nmol ml(-1)) decreased as well. Reduced (thiolic-free form) Hcy and Cys decreased during infusion, though not as pronounced as for the other forms. Percentagewise, out of the total plasma levels, Hcy and Cys total free form and reduced form tended to increase over infusion as well as their difference (i.e. the plasma mixed disulphide moiety), thus supporting the idea that excess NAC displaces thiols from their plasma binding sites forming mixed disulphides. Urinary total Cys and Hcy excretion significantly increased at the end of the day of NAC infusion (tenfold for Cys and fivefold for Hcy) and reduced appreciably on the following day. Also urinary excretion of the free form of Cys and Hcy increased at the end of the day of NAC infusion, although in a lower amount with respect of total amounts, meaning a reduction of percentage Cys and Hcy excreted as the free form; for none of the patients had proteinuria, the 'free' form of urine thiols has to be identified in the 'reduced' form, the difference between the total and free form reflecting the 'mixed disulphide' moiety. NAC intravenous administration induces an efficient and rapid reduction of plasma thiols, particularly of Hcy; our data support the hypothesis that NAC displaces thiols from their binding protein sites and forms, in excess of plasma NAC, mixed disulphides (NAC-Hcy) with an high renal clearance. This effect may represent the start of an alternative approach in the treatment of hyperhomocysteinaemic conditions.
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PMID:N -Acetyl-cysteine reduces homocysteine plasma levels after single intravenous administration by increasing thiols urinary excretion. 1052 47

Carvedilol is an antihypertensive drug with properties that may be potentially beneficial for kidney graft recipients. The purpose of the study was to investigate if progression of an established chronic rejection may be attenuated or reversed by carvedilol. An open, single-centre, phase II, pilot study, with a 2-yr follow-up, was performed in 25 kidney graft recipients with chronic rejection or accelerated transplant atherosclerosis. Seventeen patients had stable graft function assessed by serum creatinine levels. Eight patients withdrew from the study due to lack of efficacy (increase in serum creatinine 174-477 micromol/L (46-191%) from the initial levels). However. these patients had higher serum creatinine levels and proteinuria already at the start of the study. Both systolic and diastolic blood pressure, as well as heart rate, were stable in all study patients. Low density lipoprotein (LDL)/high density lipoprotein (HDL) cholesterol ratio decreased from 4.7 +/- 1.9 at 1 month to 3.5 +/- 1.2 at 18 months (p < 0.05), and MDA plasma levels decreased from 0.714 +/- 0.119 to 0.493 +/- 0.073 micromol/L after 3 months of carvedilol treatment (p < 0.05). No attenuation of progression of chronic graft rejection by carvedilol treatment was observed in the study. It is suggested that the process of chronic rejection could not be reversed by carvedilol because the patients included in the study already had severe morphological and functional changes of the graft. In conclusion, our study demonstrated that carvedilol provides a good control of blood pressure in renal transplanted patients. Carvedilol treatment had a beneficial effect on lipid pattern and reduced lipid oxidation, but there was no obvious effect on progression of chronic rejection.
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PMID:Carvedilol treatment of kidney graft recipients with chronic rejection. 1061 38

OBJECTIVES OF SYMPTOMATIC TREATMENT: The goal is to maintain quality of life, prevent immediate complications (thromboembolic events, infection, drug reactions), prevent late complications related to atherosclerosis, and limit the progression of the chronic renal failure. THERAPEUTIC ARMAMENTARIUM: Six categories can be described. i) A reduction in proteinuria, essential for controlling the intensity of other manifestations, can be improved with a normal protein content (1 g/kg ideal weight/d) low-salt diet, strict blood pressure control, and most importantly, CEI given alone or in combination with AA2. ii) Restoration of a normal extracellular fluid (edema and high BP) can be achieved by low sodium intake and loop diuretics in fractionated increasing doses (sometimes with combination regimens). It is advisable to keep blood pressure below 125/75 mmHg. iii) Prevention of thromboembolic events (risk level dependent on urine protein output) relies on antivitamin K anticoagulants and low-molecular weight heparins. iv) Adapted prescription of protein-bound drugs. v) Lowering LDL-cholesterol, a risk factor for atherosclerosis, with an adapted diet and HMG CoA inhibitors. vi) Prevention of chronic renal failure. The development and course of chronic renal failure depend not only on the histological glomerular lesion and/or the etiology but also on supplementary glomerular and tubulointerstitial damage directly related to the degree of proteinuria. MORE THAN SYMPTOM RELIEF: Symptomatic treatment of nephrotic syndrome must be considered as an integral part of a rigorous goal-oriented therapeutic strategy.
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PMID:[Symptomatic treatment of nephrotic syndrome]. 1073 12

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease marked by immune-complex mediated lesions in small blood vessels of various organs, especially the kidneys, although other factors may also be implicated in the pathogenesis of the disease. This article focuses on the role of lipids in the progression of glomerular, vascular and tubulo-interstitial lesions in two patients with lupus nephritis associated with pronounced hyper- and dyslipidemia. The pathogenesis of progressive glomerulosclerosis in both patients appears to be multifactorial. In addition to immune complex mediated lupus glomerulonephritis, progressively active in the first patient, severe nephrotic-range persistent proteinuria, arterial hypertension associated with hyperfiltration and hyperperfusion injuries and, to a minor extent, hyper- and dyslipidemia were observed. Immunological and non-immunological factors were shown to contribute to the development of tubulo-interstitial lesions. In both patients, in addition to local immune deposits, prominent tubulo-interstitial lipid deposits were probably causally related to both hyperlipidemia and the increased permeability of the glomerular filtration barrier. Tubular lesions were highlighted by intracytoplasmic lipid droplets as well as small cleft-like spaces found to be impacted in the tubular lumina. They were seen to penetrate tubular epithelial cells and eventually lodge in the interstitium, surrounded by mononuclear cell infiltrates and foam cells. In both patients, hypertensive angiopathy and extraglomerular vascular immune deposits were demonstrated. In addition, in the second patient, arteriolar and small arterial hyaline was found at the age of 28 years to be full of lipids and calcium precipitates, suggesting a peripheral atherosclerosis-like process which never occurs as a natural age-related condition. In conclusion, all parts of the nephron may be involved in the pathogenetic process causally related or influenced by hyper- or dyslipidemia. Associated either with endothelial cell injury and consequent insudation of lipids in the vascular walls, glomerular filtration barrier injury with hyperfiltration, or tubulo-interstitial lipid deposition, the mechanism of tissue damage by lipids in all parts of the nephron shares similarities with the pathogenesis of systemic atherosclerosis.
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PMID:Role of lipids in the progression of renal disease in systemic lupus erythematosus patients. 1102 Sep 63

To evaluate the biochemical and molecular mechanisms leading to glomerulosclerosis and the variable development of atherosclerosis in patients with familial lecithin cholesterol acyl transferase (LCAT) deficiency, we generated LCAT knockout (KO) mice and cross-bred them with apolipoprotein (apo) E KO, low density lipoprotein receptor (LDLr) KO, and cholesteryl ester transfer protein transgenic mice. LCAT-KO mice had normochromic normocytic anemia with increased reticulocyte and target cell counts as well as decreased red blood cell osmotic fragility. A subset of LCAT-KO mice accumulated lipoprotein X and developed proteinuria and glomerulosclerosis characterized by mesangial cell proliferation, sclerosis, lipid accumulation, and deposition of electron dense material throughout the glomeruli. LCAT deficiency reduced the plasma high density lipoprotein (HDL) cholesterol (-70 to -94%) and non-HDL cholesterol (-48 to -85%) levels in control, apoE-KO, LDLr-KO, and cholesteryl ester transfer protein-Tg mice. Transcriptome and Western blot analysis demonstrated up-regulation of hepatic LDLr and apoE expression in LCAT-KO mice. Despite decreased HDL, aortic atherosclerosis was significantly reduced (-35% to -99%) in all mouse models with LCAT deficiency. Our studies indicate (i) that the plasma levels of apoB containing lipoproteins rather than HDL may determine the atherogenic risk of patients with hypoalphalipoproteinemia due to LCAT deficiency and (ii) a potential etiological role for lipoproteins X in the development of glomerulosclerosis in LCAT deficiency. The availability of LCAT-KO mice characterized by lipid, hematologic, and renal abnormalities similar to familial LCAT deficiency patients will permit future evaluation of LCAT gene transfer as a possible treatment for glomerulosclerosis in LCAT-deficient states.
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PMID:Analysis of glomerulosclerosis and atherosclerosis in lecithin cholesterol acyltransferase-deficient mice. 1127 14

Lectinlike oxidized LDL receptor-1 (LOX-1), a cell-surface receptor for oxidized LDL (ox-LDL), is proposed to be involved in endothelial dysfunction and in the pathogenesis of atherosclerosis. Preeclampsia is a pregnancy complication diagnosed by hypertension and proteinuria, characterized by endothelial dysfunction, and supposedly caused by compounds from hypoxic uteroplacental tissues. A feature of preeclampsia is formation of foam cells in maternal arterial walls of gestational tissue ("acute atherosis"). Oxidative stress is believed to play a role in the pathophysiology of preeclampsia. 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) is a marker of oxidative stress in vivo, is biologically active in vitro, and is elevated in preeclamptic plasma and gestational tissue. In the present article, we hypothesized that 8-iso-PGF(2alpha) could induce the expression of LOX-1 in trophoblastic cells (JAR). We demonstrated augmented cellular uptake of (125)I-tyraminylcellobiose ox-LDL in JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L) versus control cells. Ligand blots revealed an increased binding of ox-LDL to LOX-1 in JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L). Incubation with 8-iso-PGF(2alpha) (10 micromol/L) also resulted in augmented LOX-1 protein levels (Western blots) and mRNA levels (Northern blots). JAR cells transfected with 3 copies of a nuclear factor-kappaB binding site demonstrated dose-dependent activation of the reporter gene luciferase after incubation with 8-iso-PGF(2alpha) (0 to 10 micromol/L). We also demonstrated increased accumulation of neutral fats in JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L) and ox-LDL compared with controls by oil red O staining. We speculate a potential role of isoprostanes and LOX-1 in preeclampsia in the development of "acute atherosis" of gestational spiral arteries.
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PMID:8-iso-prostaglandin F(2alpha) increases expression of LOX-1 in JAR cells. 1130 22

CS-866 is a new angiotensin II receptor blocker that has demonstrated effectiveness for lowering blood pressure in animal models of hypertension. Given the proposed involvement of the renin-angiotensin system in diabetic nephropathy and atherosclerosis, we have tested CS-866 in animal models of these conditions. The renal protective properties of CS-866 were examined in the Zucker diabetic fatty (ZDF) rat, a model of type 2 diabetes that develops progressive hyperglycemia, glomerulosclerosis, and proteinuria. Treatment of ZDF rats with CS-866 in the diet for 19 weeks resulted in a dose-dependent reduction in urinary protein excretion compared with vehicle-treated control rats, which was independent of changes in blood pressure and glycemic state. The antiatherosclerotic properties of CS-866 were tested in 2 animal models. In the first study, cynomolgus monkeys were fed a high-cholesterol diet for 6 months while receiving CS-866 or vehicle. At the end of this period, CS-866-treated animals had 64% less plaque area in the aorta than controls. CS-866 was also tested in the Watanabe heritable hyperlipidemic (WHHL) rabbit model of atherosclerosis. WHHL rabbits were treated for 32 weeks with CS-866 (1 mg/kg), pravastatin (50 mg/kg), a combination of the 2 drugs, or vehicle. CS-866 had no effect on plasma cholesterol levels and reduced blood pressures minimally. Pravastatin alone reduced serum cholesterol but had no effect on blood pressure or lesion area. In contrast, treatment with CS-866 resulted in a 40% reduction in lesion area compared with vehicle-treated control when given alone and a 50% reduction in combination with pravastatin. On the basis of results from animal models, CS-866 may be a useful treatment for diabetic nephropathy and atherosclerosis.
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PMID:New pharmacologic aspects of CS-866, the newest angiotensin II receptor antagonist. 1133 66

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