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)

Although the precise etiologic incitant of the minimal lesion idiopathic nephrotic syndrome of childhood is not known, it is likely that a host mechanism mediates the permeability alterations of the glomerular capillary wall resulting in massive proteinuria. As a first step in examining the possibility that local kinin release may account for the proteinuria in this disorder, two parameters of the plasma kinin-generating system, plasma prekallikrein and kallikrein inhibitor, were assayed during 27 nephrotic episodes in 21 corticosteroid-responsive children. Plasma kallikrein was assayed by means of its esterase activity on a synthetic arginine ester substrate, N-alpha-tosyl-L-arginine methyl ester (TAMe), after activation of Hageman factor by kaolin. This activity, after subtraction of spontaneous arginine esterase activity (i.e., TAMe esterase activity measured in plasma not exposed to kaolin) is derived from prekallikrein. Plasma prekallikrein activity in 11 normal children was 99.6 +/- 2.9 mumol TAMe hydrolyzed/ml plasma/hr (mean +/- SEM). Kallikrein inhibitor was quantified in arbitrary units. Kallifrein inhibitor activity in 11 normal children was 0.94 +/- 0.04 units. During the overt nephrotic syndrome, before initiation of intensive daily corticosteroid treatment, mean values were: prekallikrein, 58.5 +/- 7.24 mumol/ml/hr; and kallikrein inhibitor, 0.35 +/- 0.06 units. After corticosteroid-induced remission occurred, mean values were: plasma prekallikrein, 118.6 +/- 3.2 mumol/ml/hr; and kallikrein inhitor, 0.78 +/- 0.03 mumol/ml/hr. Both parameters were again assayed in 14 of the 21 children after complete cessation of corticosteroid treatment. Plasma prekallikrein was normal, 99.6 +/- 4.8 mumol/ml/hr; but kallikrein inhibitor was still somewhat depressed, 0.84 +/- 0.03 units. A subset of 9 patients had marked depression of plasma prekallikrein to levels less than 20 mumol/ml/hr and essentially undetectable inhibitor activity. Serum alpha-2 macroglobulin was elevated in nephrotic patients: mean value during relapse, 862 +/- 29 mg/100 ml; during corticosteroid-maintaining remission, 615 +/- 29 mg/100 ml. After cessation of corticosteroids, mean serum level was 481 +/- 20 mg/100 ml. The proportional reduction of plasma prekallikrein and kallikrein inhibitor suggested that an enzyme-inhibitor complex formed in vivo, perhaps at a local site of activation in proximity to the glomerular basement membrane. These data suggest that the plasma kinin-generating system may be the host effector mechanism subserving the increased glomerular capillary permeability in the minimal lesion nephrotic syndrome of childhood.
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PMID:A study of the plasma kinin-generating system in children with the minimal lesion, idiopathic nephrotic syndrome. 5 8

Main components of kinin system, the arginine-esterase activity and proteinase inhibitors were estimated in blood serum of patients with nephrotic syndrome of various etiology (glomerulonephritis, amyloidosis, systemic lupus erythematous) and also in patients with latent nephritis and in healthy donors. Content of all the kinin system components (kallikreinogen, kininogen and kininase 1) proved to be increased in all the forms of nephropathy studied. Free kallikrein was found in blood serum of patients with nephrotic syndrome as distinct from healthy persons and patients with latent nephritis. The arginine-esterase activity, which shows the level of trypsin-like proteinases, was altered dissimilarly, depending on the nephrotic syndrome etiology: it was maximally increased in nephrotic syndrome of amyloid genesis and decreased in patient with systemic lupus erythematosus. High content of kallikrein and kininase I with simultaneous decrease in kininogen was typical for patients with severe form of nephrotic syndrome. Impairment of kidney in nephrotic syndrome was also characterized by an increase in alpha1-antitrypsin and in the total antitryptic activity, which reached the maximal value in nephrotic syndrome of the I degree and decreased at the II degree of the disease. In nephrotic syndrome content of alpha2-macroglobulin was maximally increased at the II degree of nephrotic syndrome and decreased in severe form of the disease. The primary alteration in content of proteinase inhibitors and high level of kinin system components were assumed to determine the conditions for activation of kinin system in blood serum and to impair the nephrotic syndrome pathogenesis, which was complicated by systemic manifestations. High content of kinin system components was apparently determined by the increased synthesis in liver tissue in response to inflammation and massive proteinuria; kininase I and alpha2-macrolgobulin, as proteins with high molecular weight, were likely to be selectively retained in blood circulation when the capillary penetration was increased.
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PMID:[State of the kinin system and level of serum proteinase inhibitors in latent nephritis and the nephrotic syndrome of different etiology]. 7 Jan 11

A case is described in which a patient developed TT prolongation and bleeding during CMV hepatitis following successful renal transplantation. Bence-Jones proteinuria was noted, but there was no other evidence of myeloma. Bence-Jones proteinuria, TT prolongation, and bleeding abated as hepatitis resolved. In vitro, a protein isolated from the patient's urine was capable of prolonging the TT markedly, but it did not impair thrombin esterase activity. The effect of the protein seemed to be inhibition of fibrin polymerization. Sephadex gel filtration revealed a single TT-prolonging peak at 11,000 daltons, containing kappa, lambda, and delta antigens. By radioimmunoassay, virtually all the protein present reacted as beta2-microglobulin. Incubation with anti-beta2-microglobulin antiserum markedly attenuated anticoagulant activity. The paraprotein observed transiently in this patient's urine during hepatitis had potent anticoagulant activity and may well have accounted for his abnormal TT and bleeding diathesis; this paraprotein was not distinguishable from beta2-microglobulin.
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PMID:Impaired fibrin polymerization in viral hepatitis. Report of a case: probable identity of the inhibitor with beta2-microglobulin. 21 57

We have investigated the pathogenesis of glomerular hypercellularity seen in acute serum sickness nephritis induced in rabbits with bovine serum albumin (BSA). The increase in cellularity began with the first stages of immune clearance of BSA, with a peak cellularity occuring at the time of onset of proteinuria. Although there was a significant increase in the fraction of glomerular cells incorporating [3H]thymidine, first seen at the onset of proteinuria, this increase occurred too late and was too small to explain the observed rate of increase in glomerular cellularity. On the other hand, a striking monocytic infiltration of the glomeruli was documented by electron microscopy and by staining for nonspecific esterase. This monocytic infiltration paralleled the observed course of glomerular hypercellularity and was quantitatively sufficient to explain the total increase seen. It appears, therefore, that glomerular hypercellularity seen in this model is principally a result of monocyte infiltration.
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PMID:The role of monocytes in serum sickness nephritis. 47 58

Monocytes have been demonstrated to play an important role in acute serum sickness (AcSS) nephritis. Because accumulation of monocytes within the glomeruli could be the result of local lymphokine production, we studied migration inhibition factor (MIF) activity in supernatants from glomerular cultures, analyzed its temporal relationship with monocyte and lymphocyte accumulation, and tested the effect of anti-T lymphocyte monoclonal antibody on local MIF production. AcSS was induced in 12 rabbits, and one additional rabbit had antigen elimination without proteinuria. Single nephrectomy was performed at the time of antigen elimination in all animals; the remaining kidney was removed four days (4 rabbits) or 14 days afterwards (5 rabbits). In glomerular cross sections (gcs), lymphocytes were identified using monoclonal antibody M108, and monocytes by nonspecific esterase stain (ES). MIF activity was determined in supernatants of cultures of isolated glomeruli by the agarose microdroplet method. Peak of MIF activity (84.3 +/- 2.6%, SEM) was observed the first day of proteinuria in association with peak of lymphocyte infiltration (1.15 +/- 0.1 lymphocytes/gcs) and monocyte infiltration (2.4 +/- 0.3 mean ES score/gcs). MIF activity diminished by day 4 (66.0 +/- 6.3%) and reached control levels by day 14 (12.8 +/- 3.2%). There was a significant correlation between lymphocyte infiltration and MIF activity (r = 0.776, P less than 0.0001) as well as between MIF activity and monocyte accumulation (r = 0.858, P less than 0.0001). In five additional rabbits with AcSS, glomeruli were isolated, treated successively with M108 and normal rabbit serum, and supernatants harvested from 24-hour cultures were tested for MIF activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Migration inhibition factor in acute serum sickness nephritis. 207 55

The ability of a urinalysis reagent strip to predict the presence of formed elements in the sediment was evaluated. The sensitivity of individual biochemical analytes varies from 0.51 to 0.85; however, the combined sensitivity of positive reactions for either protein, nitrite, leukocyte esterase, and/or hemoglobin is 0.95. Leukocyte esterase activity becomes detectable at a concentration of 15 white blood cells per high-power field (WBCs/HPF). Proteinuria is nonspecifically related to pyuria and detects a minimum concentration of 6 WBCs/HPF, and the hemoglobin reaction detects 6 red blood cells/HPF. Most false negative reactions are associated with bacteriuria. A positive chemical reagent strip test can be safely and effectively used as a prerequisite for routine urine microscopic examination.
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PMID:Eliminating unnecessary urine microscopy. Results and performance characteristics of an algorithm based on chemical reagent strip testing. 230 Dec 96

The present study provides a histochemical analysis of the macromolecular and cellular composition of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) in the rat with special reference to the different types of lipids present and to the participation of monocytes. FSGHS was induced in male Wistar rats by unilateral nephrectomy (UN) or puromycin aminonucleoside (PAN) injections. Histochemical analysis of glomeruli with FSGHS in both models after 20 weeks of proteinuria revealed massive deposits of lipids. These lipid accumulations were shown to consist mainly of free and esterified cholesterol; triglycerides and phospholipids were present in small amounts. Monocytes, identified by the alpha-naphthyl acetate method for non-specific esterase activity were scanty in glomeruli affected by FSGHS with an average glomerular count of 0.1 in UN- and 0.2 in PAN-treated rats. When present, no preferential localization of monocytes in the lesions was observed. The progressive glomerular damage occurring once the process of hyalinosis and sclerosis has started may be related to the paucity of "scavenging" monocytes. Cholesterol may be one of the substances involved in the development of these glomerular changes.
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PMID:Glomerular sclerotic lesions in the rat. Histochemical analysis of their macromolecular and cellular composition. 287 25

To evaluate the role of macrophages in glomerulonephritis, the relationship between the existence of macrophages and proteinuria in the long course of glomerulonephritis was studied in accelerated Masugi nephritis in the rat. Non-specific esterase staining was used as a marker of macrophages and the kinetics of glomerular macrophages was analysed by an image processor. Macrophages became detectable 48 hours after nephrotoxic serum injection and their accumulation reached a maximum level at 5 days. At 1 month, they had clearly decreased. At 3 months, however, many macrophages were found within the capsular drop-like lesions and crescents. Urinary protein excretion took roughly the same time course as the number of macrophages for 2 weeks. However, at 1 month, whereas macrophages had decreased, the proteinuria kept a persistently high level. At 3 months it showed a tendency to decrease. The correlation between the rate of appearance of macrophages and the urinary protein excretion assessed in 20 cases exhibited no significance. In addition, discrepancy in their time course was evident at 1 month. Although macrophages may happen to contribute to the tissue injury resulting in proteinuria in the early phase of nephrotoxic serum nephritis, factors other than macrophages should be considered in the subsequent duration of proteinuria in this model.
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PMID:Macrophages in glomerular injury. I. The kinetics of macrophages in accelerated Masugi nephritis in the rat. 315 78

In order to investigate the validity of urinary kallikrein (KAL) measurement, comparative studies were performed among the values obtained by various methods of urinary KAL measurements. Daily urine samples were collected from 37 hospitalized normal subjects (NS, 21 essential hypertensives without complications (EHT) and 20 patients with renal diseases associated with proteinuria (PU). Urinary KAL excretions were determined by direct radioimmunoassay (RIA), kininogenase assay (K-genase), TAMe esterase assay (TAMe), and PPA-MCA (MCA) and PPA-NE amidase assay (NE). By the desalting procedure, urinary KAL levels showed significant changes in TAMe, MCA and NE, but not in d-RIA and K-genase in all three groups. In TAMe, MCA and NE, the recovery of added KAL in urine was significantly lower in non-desalted samples in both EHT and PU, but not in NS. Impaired recovery and correlations between d-RIA or K-genase and TAMe, MCA or NE in non-desalted samples were improved by desalting. Although good correlations were observed between d-RIA or K-genase and TAMe, MCA or NE in desalted samples, the slopes of curves were steeper in EHT and PU than in NS, suggesting that the synthetic substrate methods still have some problems in the KAL measurement in these pathological states, KAL inhibitor, aprotinin and gabezate mesilate did not suppress the esterclytic and amidolytic activities completely, but suppressed K-genase activity completely in PU urine samples, suggesting that certain kinds of non-KAL esterases might remain in PU urine samples. Thus, d-RIA and K-genase appear to be the most reliable methods in the measurement of urinary KAL quantity and activity, respectively.
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PMID:A comparative study of the measurement of urinary kallikrein by various methods in patients with essential hypertension and patients with proteinuria. 364 32

Glomerular monocyte infiltration was evaluated by histochemical means (nonspecific esterase) and/or electron microscopy in 305 renal biopsies belonging to a wide variety of human renal diseases. Significant monocyte infiltration was never observed in a first group of nepropathies (minimal change disease, nephrotic syndrome with IgM deposits, focal segmental glomerulosclerosis, membranous GN, Berger's GN, healed GN, dense deposit disease, chronic non specific GN, benign familial haematuria, Alport's disease, renal amyloidosis, arteriosclerotic kidney, light chain GN). Conversely, it was present at varying frequency in a second group of nephropathies including: acute GN (58.3%), persistent GN (10%), membranoproliferative GN (25.2%), eryoglobulinaemic GN (82.6%), lupus GN (36%), extracapillary proliferative GN (50%) and Schoenlein-Henoch GN (40%). The results indicate: 1) there is an evident association between monocyte infiltration and the subendothelial site of deposits; 2) the presence of monocytes is not affected by the size and extension of subendothelial deposits; 3) monocytes were more frequently observed when IgG, IgM and fibrinogen were present in the subendothelial deposits, Conversely, complement fractions do not seem to affect monocytic activity; 4) polymorphonuclear leukocyte exudation is less frequently found and mostly associated with monocyte infiltration; 5) in some GNs (persistent GN, cryoglobulinaemic GN and membranoproliferative GN), proteinuria was significantly higher in patients with than in those without monocyte infiltration, giving support to the hypothesis that in human beings as in experimental animals monocytes play a role in the pathogenesis of proteinuria.
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PMID:Glomerular monocyte infiltration in human nephropathies: prevalence and correlation with clinical and morphological variables. 392 Aug 20


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