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 prevalence of bacteriuria as well as bacterial virulence and host factors were studied in 514 diabetic outpatients and 405 nondiabetic controls. The prevalence of bacteriuria was not significantly higher in diabetic women (15/239, 6.3%) than in age-matched nondiabetic women (8/236, 3.4%). In diabetic and nondiabetic men, the prevalence was also similar but lower than in women. E. coli was found in 55% of urine cultures with significant growth from diabetic patients, while in 91% of positive cultures from nondiabetic controls. Most E. coli strains lacked ability of P-fimbriae-mediated adhesion and aerobactin-mediated iron uptake, indicating low bacterial virulence. Long-term metabolic control (HbA1c), prevalence of retinopathy, neuropathy and previous foot ulcers were similar in bacteriuric and nonbacteriuric diabetic patients, matched according to gender, age, and duration of diabetes. Renal function was also similar, though the frequency of proteinuria and elevated blood pressure tended to be higher in the bacteriuric than in the noninfected group. Eight-three percent of the bacteriuric patients reported previous urinary tract infections but only 61% of nonbacteriuric patients (p = 0.07). As compared to non-diabetic women, diabetic women reported significantly more previous urinary tract infections (p < 0.01). In conclusion, the prevalence of bacteriuria in diabetic outpatients was not significantly higher than in non-diabetic outpatients or healthy volunteers. No studied host factor was clearly associated with bacteriuria in diabetic patients, although proteinuria and hypertension tended to be more common. The infecting E. coli strains were of low virulence.
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PMID:Bacteriuria, bacterial virulence and host factors in diabetic patients. 836 92

Diabetic patients, as compared to non-diabetic subjects, run an increased risk of acquiring Gram-negative bacteraemia. We therefore studied the prevalence and coexpression of seven bacterial virulence markers of 69 Escherichia coli strains isolated from 64 bacteraemic patients with diabetes mellitus and 67 E. coli strains from faeces of healthy controls. The strains were analyzed for haemolysin (HLY) production, aerobactin-mediated iron uptake (AMI), cytotoxic necrotizing factor (CNF) production, expression of cell surface hydrophobicity, P-fimbriae, mannose-resistant haemagglutination (MRHA) and mannose-sensitive haemagglutination (MSHA). All bacterial properties were significantly more common among the bacteraemic strains (P < 0.02 vs. controls). Correlations between HLY and CNF (P < 0.0004) and between P-fimbriae and MRHA (P < 0.0001), MSHA (P < 0.0002) or AMI (P < 0.05), as well as between MRHA and MSHA (P < 0.0005) were observed. In patients with proteinuria, as sign of diabetic complications in the urinary tract, HLY-negative strains, P-fimbriae-negative strains, and strains which were both HLY-/CNF-negative, were more common (P = 0.04, P < 0.01 and P = 0.048, respectively). Using a multivariate statistical analysis, production of HLY and the expression of P-fimbriae were the two virulence factors with the highest discrimination between bacteraemic and control strains. In conclusion, all virulence factors studied were more prevalent in bacteraemic than in control strains, although HLY and P-fimbriae were shown to be of greatest and independent importance. Low virulent strains (P-fimbriae-, HLY- and CNF-negative) were more prevalent in diabetic patients with signs of renal complications.
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PMID:P-fimbriation and haemolysin production are the most important virulence factors in diabetic patients with Escherichia coli bacteraemia: a multivariate statistical analysis of seven bacterial virulence factors. 852 28

A 9-year-old boy with typical features of congenital erythropoietic porphyria who had received more than 50 blood transfusions developed the steroid-resistant nephrotic syndrome in the presence of normal glomerular function and glucosuria. Renal biopsy showed focal segmental glomerulosclerosis and widespread iron deposits. Magnetic resonance scanning revealed advanced siderosis of liver and kidneys. During a 4 year treatment by desferrioxamine the serum ferritin level was reduced, proteinuria dropped and serum proteins increased whilst glomerular filtration decreased slowly. It is suggested that the nephrotic syndrome may be a consequence of renal siderosis amenable to iron-chelating therapy.
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PMID:Congenital erythropoietic porphyria associated with nephrotic syndrome and renal siderosis. 858 Jun 39

The cause of the relentless progression of chronic renal failure of diverse origins remains unknown and is likely to be multifactorial. Numerous studies have now demonstrated a correlation between the degree of proteinuria and the rate progression of renal failure, which has led to the hypothesis that proteinuria may be an independent mediator of progression rather than simply being a marker of glomerular dysfunction. This article reviews the evidence underlying this hypothesis and the mechanisms by which particular proteins may cause renal pathology. The abnormal filtration of proteins across the glomerular basement membrane will bring them into contact with the mesangium and with the tubular cells. There is evidence to support a role of lipoproteins on mesangial cell function, which ultimately could contribute to glomerular sclerosis. The proximal tubular cells reabsorb proteins from the tubular fluid, which leaves them particularly vulnerable to any adverse effects proteins may have. It has been postulated that the sheer amount of protein to be metabolized by these cells may overwhelm the lysosomes and result in leakage of cytotoxic enzymes into the cells. In addition, the increased metabolism of proteins may result in production of ammonia, which can mediate inflammation through activation of complement. Specific proteins that have been shown to be cytotoxic are transferrin/iron, low-density lipoprotein, and complement components, all of which appear in the urine in proteinuric states. Other specific proteins have been shown to stimulate production of cytokines, chemoattractants, and matrix proteins by tubular cells and thus may stimulate interstitial inflammation and scarring. The mechanisms by which the presence of proteins in the tubular fluid alters tubular cell biology is yet to be determined.
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PMID:The role of proteinuria in the progression of chronic renal failure. 865 Dec 39

Treatment of minimal change disease, like most glomerulonephritides, is empirical because underlying mechanisms that cause glomerular injury are not known. We examined a pathogenic role of 'catalytic' iron in a model of minimal change nephrotic syndrome induced by injection of puromycin aminonucleoside (7.5 mg/100 g body wt) to rats. Although there was no significant change in non-heme iron content in glomeruli, the bleomycin-detectable iron (capable of catalyzing free radical reactions) was markedly increased in glomeruli from nephrotic rats when compared to control. In contrast, despite a marked and significant increase in the non-heme iron content in tubules, there was no significant change in the bleomycin-detectable iron in tubules from nephrotic rats. In a separate in vivo study, the iron chelator, deferoxamine, prevented the increase in the bleomycin-detectable iron in glomeruli and provided complete protection against proteinuria. Taken together, our data suggest an important pathogenetic role for glomerular catalytic iron in the puromycin aminonucleoside-induced minimal change nephrotic syndrome.
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PMID:Role of 'catalytic' iron in an animal model of minimal change nephrotic syndrome. 882 19

Clinical and experimental data have indicated that heavy proteinuria in renal glomerular diseases is associated with the formation of tubulointerstitial fibrosis and contributes to the progression of renal failure. In recent years studies have focused on the possibility that albumin and other proteins that accumulate in the lumen of proximal tubular cells as a consequence of glomerular permeability dysfunction, are a direct cause of tubular cell injury. Specific proteins that have been shown to be cytotoxic are transferrin/iron, lipoproteins and complement components, all of which appear in the urine in proteinuric states. As an additional pathway of injury one may consider the effects of lipids bound to albumin and lipoproteins, including oxidized low density lipoproteins, which, by inducing an oxidative stress to tubular cells, are potent cytotoxic molecules. Moreover, reabsorption of high molecular weight proteins activates proximal tubular cells to produce matrix proteins, cytokines, chemoattractants and vasoactive mediators that may-converge in stimulating interstitial inflammation and scarring. Given the functional toxicity of filtered proteins on the kidney, pharmacological and dietary manipulations aimed at reducing glomerular protein traffic may have a beneficial impact on the deterioration of renal function in progressive nephropathies.
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PMID:Role of increased glomerular protein traffic in the progression of renal failure. 935 Jun 74

1. Proximal tubular cell dysfunction in chronic glomerular disease (CGD) has been ascribed, in part, to reabsorption of transferrin-iron from tubular fluid and subsequent cytosolic peroxidative injury. To investigate a possible role for altered mitochondrial function in tubular cell injury in CGD, renal cortical mitochondrial respiratory function was examined in rats with adriamycin nephrosis. 2. State 4 (resting) respiration was increased in adriamycin nephrosis in comparison with control (51 +/- 2 vs 43 +/- 2 ng atoms oxygen (O)/min per mg protein, respectively; P < 0.02). 3. Mitochondrial iron concentration was increased in nephrotic rats compared with control (9.52 +/- 0.70 vs 5.97 +/- 0.26 nmol Fe/mg protein, respectively; P < 0.001) and rates of state 3, state 4 and uncoupled respiration and the severity of proteinuria correlated with mitochondrial iron concentration. 4. To further define the relationship between mitochondrial iron accumulation and altered respiratory function, rats were loaded with iron. 5. In comparison with control, acute iron loading of normal rats impaired creatinine clearance (1.48 +/- 0.02 vs 0.40 +/- 0.29 mL/min), increased kidney weight (1.33 +/- 0.07 vs 1.74 +/- 0.14 g) and impaired mitochondrial enzyme activity (e.g. cytochrome oxidase 185.0 +/- 46.6 vs 362.0 +/- 32.8 delta log [cytochrome C]/min per mg protein; P < 0.05), but had no significant effect on rates of mitochondrial respiration or on mitochondrial fragility. 6. Mitochondrial iron concentration was not increased by iron loading, despite a similar increment in cytoplasmic iron to that seen in rats with adriamycin nephrosis. 7. In summary, resting mitochondrial respiration is increased in nephrotic rats in proportion to mitochondrial iron accumulation. Changes in mitochondrial oxygen consumption do not appear to be a primary event in the tubular cell injury of iron loading.
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PMID:Mitochondrial function in rat renal cortex in response to proteinuria and iron. 940 56

Proteinuria has been invoked as a cause of tubulointerstitial injury in chronic renal disease, and in vivo studies have suggested indirectly the particular nephrotoxicity of one urinary protein holotransferrin (Tf-Fe). However, to date there has been no direct evidence for the nephrotoxicity of Tf-Fe. To examine the potential cytotoxicity of Tf-Fe and the mechanism involved, and to compare this to another urinary protein albumin, rat proximal tubule cells were studied in primary culture. Tf-Fe at pH 6.0 caused functional and ultrastructural injury, but no cytotoxicity was seen with cells exposed to albumin, apotransferrin (transferrin), or Tf-Fe at pH 7.4. The influence of pH on Tf-Fe-induced cytotoxicity was not due to pH per se, but could be explained by an effect on Tf-Fe uptake. At pH 6.0, uptake of 125I-Tf-Fe (3.55 +/- 0.05 versus 1.25 +/- 0.10 fmol/dish, P < 0.01) and intracellular iron concentration (1.14 +/- 0.25 versus 0.46 +/- 0.23 nmol/dish, P < 0.01) were increased compared with values at pH 7.4. In contrast, pH 6.0 did not increase iron uptake from FeCl3. Lysine (100 mM) inhibited Tf-Fe uptake, decreased intracellular iron concentration, and attenuated Tf-Fe-induced cytotoxicity. The iron chelator des-ferrioxamine (200 microM) and hydroxyl radical scavenger dimethylpyrroline N-oxide (32 mM) abolished lactate dehydrogenase leakage induced by Tf-Fe at pH 6.0. Lipid peroxidation, as assessed by production of malondialdehyde, preceded lactate dehydrogenase leakage. In summary, holotransferrin, but not albumin, is toxic to rat proximal tubule cells, a pH-dependent effect involving its uptake into tubule cells, its iron moiety, and its lipid peroxidation.
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PMID:Toxicity of holotransferrin but not albumin in proximal tubule cells in primary culture. 944 90

Heme oxygenase (HO) catalyses degradation of heme to biliverdin, iron and carbon monoxide (CO). Two isoforms exist, a constitutive form and an inducible form (HO-1). Induction of HO-1 may have protective effects in inflammation. We studied heterologous (HNTN) and accelerated (ANTN) nephrotoxic nephritis in Lewis rats. Hemin, an inducer of HO-1, (30 mumol/kg) was administered 18 hours before induction of nephritis and 72 hours later in ANTN. HO-1 was not detected immunohistochemically in normal glomeruli but was present in HNTN and ANTN in cells with the morphology of macrophages. HO-1 induction was confirmed by RT-PCR. In normal rats hemin induced glomerular HO-1 mRNA at 18 hours. In HNTN hemin markedly reduced proteinuria at 24 hours (10 +/- 4 mg/24 hr; control 54 +/- 16; P < 0.05), neutrophil infiltration at two hours (29.8 +/- 1.8 vs. 22.3 +/- 1.5 neutrophils/glomerulus, P < 0.05), and glomerular macrophage number at two hours (2.1 +/- 0.1 vs. 3.1 +/- 0.4 cells/glomerulus, P < 0.05). In ANTN proteinuria was reduced at day 1 and day 4 (36 +/- 11 vs. 60 +/- 15 and 36 +/- 7 vs. 86 +/- 9 mg protein/24 hr, respectively, P < 0.001), glomerular thrombi were reduced by hemin at day 1 and 4 (1.5 +/- 2.7 vs. 2.7 +/- 0.2 and 1.3 +/- 0.01 vs. 2.9 +/- 0.02, respectively, P < 0.001) and glomerular macrophage infiltration was reduced on day 4 (11.2 +/- 0.8 cells/glom; control 15.9 +/- 0.8, P < 0.01). Possible mechanisms by which HO-1 ameliorates disease include anti-complement or anti-oxidant effects of bilirubin and vasodilator and anti-platelet effects of carbon monoxide.
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PMID:Heme oxygenase is induced in nephrotoxic nephritis and hemin, a stimulator of heme oxygenase synthesis, ameliorates disease. 950 13

A 12-year-old girl with a main complaint of sever pain on the both knees was admitted to our hospital in October, 1995. She gave a three year history of recurrent arthralgia and purpuric rashes, and persistent microhematuria and proteinuria. She developed vesicles and purpuric rashes on the hands and auricles, morning stiffness, fever, uveitis and pericarditis. Laboratory findings showed an elevated level of erythrocyte sedimentation rate and iron-deficiency anemia. Serum perinuclear pattern ANCA with antimyeloperioxidase specificity (MPO-ANCA) was positive. A renal biopsy specimen disclosed a focal and segmental necrotizing glomerulonephritis with crescents. Our case fulfills the both diagnostic criteria for polyarteritis nodosa and juvenile rheumatoid arthritis. This is a rare case of MPO-ANCA associated vasculitis in children.
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PMID:[A case of juvenile rheumatoid arthritis with MPO-ANCA associated nephritis]. 956 75


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