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)

We reviewed the initial serological data of 50 patients with biopsy-proven lupus nephritis. As compared with a group of lupus patients without nephritis, patients with nephritis had lower serum complement C3 (p less than 0.05) and C4 (p less than 0.005) levels and higher serum DNA binding activity (p less than 0.001). The frequency of rheumatoid factor, antiphospholipid, anti-ENA, and fluorescent antinuclear antibodies was similar in both groups. We correlated the serological data of the patients with nephritis with the clinical severity of their disease. Using a functional staging system based on the serum albumin and creatinine levels at the time of biopsy, we found that patients with functionally milder disease (proteinuria without nephrotic syndrome or renal failure) had higher C3 (p less than 0.05) and lower DNA binding (p less than 0.005) than patients in the more severe functional classes (nephrotic syndrome with or without renal failure). In contrast, C4 levels were always very low, irrespective of functional severity. We also correlated the serological data with the pathological findings. Patients suffering from diffuse proliferative nephritis had higher DNA binding values than patients with focal proliferative (p less than 0.01) or membranous (p less than 0.001) nephritis. By contrast, complement levels were not correlated with the severity of biopsy changes. Taken together, the data presented here suggest that C3 and DNA binding, but not C4, correlate with the clinical severity of lupus nephritis at presentation whereas DNA binding, but not complement levels, correlates with the severity of pathological changes.
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PMID:Lupus nephritis: the significance of serological tests at the time of biopsy. 193 81

To evaluate renal terminal complement activation in patients with glomerular diseases, we measured terminal complement complexes (TCCs) in plasma and urine with sandwich enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody against a C9 neoepitope expressed on TCC and a polyclonal antihuman C7 antibody. TCCs were detectable in plasma but not in urine in most of normal controls. In plasma, TCC levels were elevated in 4 of 22 patients with lupus nephritis and in 6 of 12 with membranoproliferative glomerulonephritis. However all patients with IgA nephritis, focal glomerulosclerosis, idiopathic membranous nephritis and idiopathic minimal change nephrotic syndrome (MC) showed normal values. In urine, TCCs were detectable in almost all patients with heavy proteinuria (greater than or equal to 100 mg/ml) except MC. The TCCs present in urine were partially purified by gel filtration using Sepharose 6B and were found to contain C5, C6, C7, C8, C9 and S protein by ELISA. Although the molecular weight of TCC is similar to that of IgM, the fractional excretion rate of TCC was about 100 times higher than that of IgM. These results suggest that TCCs detectable in urine contain SC5b-9 complexes and are mostly of renal origin.
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PMID:Urinary excretion of terminal complement complexes in glomerular disease. 194 44

Untreated 16-week-old MRL/MpJ-lpr/lpr (lpr) mice, when compared to congenic MRL/MpJ-+/+ (+/+) mice, are characterized by a systemic lupus erythematosus syndrome, including severe glomerulonephritis, proteinuria and reduction of renal function. We hypothesized that platelet activating factor (PAF), a potent chemotactic and proinflammatory phospholipid mediator synthesized and released by circulating cells, glomerular mesangial and renal medullary interstitial cells, may play a role in the development of renal injury in lupus mice. We assessed renal PAF synthesis in lpr as well as +/+ mice and the effect of treatment with a PAF receptor blocking agent. Treatment with the PAF receptor antagonist L659,989 for four weeks, starting at 12 weeks of age, significantly reduced acute glomerular infiltration and proliferation, and prevented chronic glomerular histological changes; proteinuria and serum creatinine levels were also significantly reduced in treated mice. Renal PAF production was increased in lpr when compared to +/+ mice, and treatment with L659,989 restored renal PAF synthesis to the control levels. Our results support the hypothesis that PAF can be one of the mediators of glomerular injury characteristic of murine lupus nephritis, and indicate the possible therapeutic utility of PAF receptor antagonists in immunologic renal diseases.
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PMID:Platelet activating factor receptor blockade ameliorates murine systemic lupus erythematosus. 196 46

MRL-lpr/lpr mice develop T cell lymphadenopathy, polyclonal activation of B lymphocytes, autoantibodies and lupus nephritis. B and T cell populations, the dysfunctions of which play a role in the pathophysiology of the mouse disease, represent potential targets for lupus treatment. MRL-lpr/lpr mice are treated from the age of 19 weeks, i.e. after the onset of renal disease and lymphoproliferation, with Cyclosporin A which acts at the T cell level, or with DIAM4 which can down modulate polyclonal activation of B lymphocytes. DIAM4 induces the disappearance of the lymphoproliferation, the increase in C3 levels and the decrease in anti-DNA antibody, immunoglobulin and urea levels, and proteinuria. Cyclosporin A reduces lymph node hyperplasia, but has no effect on other parameters of the disease.
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PMID:Treatment of end stage MRL-1pr/lpr mouse lupus disease by a cyclophosphazene derived drug and by cyclosporin A. 196 44

Platelet activating factor (PAF) is present in urine from humans and experimental animals in normal conditions. Very little is known about changes in PAF urinary excretion under pathologic conditions and no data are available about the origin of PAF in the urine. In the present study we explored the possibility that immunologic renal disease is associated with an increase in PAF urinary excretion using gas chromatography-mass spectrometry technique. To clarify the renal or extrarenal origin of urinary PAF we evaluated whether exogenously administered PAF (1-[1', 2'-3H]alkyl) is filtered through the glomerulus and excreted in the urine. The results show that: 1) urine from mice with lupus nephritis in the early phase of the disease contained amounts of PAF comparable to those excreted in normal mouse urine, 2) PAF levels increased when animals started to develop high grade proteinuria, 3) after intravenous injection of [3H] PAF in nephritic mice, a negligible amount of [3H] ether lipid, corresponding to [3H]1-alkyl -2-acyl-3-phosphocholine (alkyl-2-acyl-GPC), was recovered from the 24 h urine extract.
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PMID:Increased urinary excretion of platelet activating factor in mice with lupus nephritis. 201 Oct 46

Patients with diffuse, proliferative lupus nephritis (DPLN) were subjected to differential solute clearances (n = 22) and serial renal biopsy (n = 11) before and again after 6-12 mo of immunosuppressive therapy. Glomerular sieving of dextrans of graded size was analyzed with a heteroporous membrane model. This revealed active DPLN to be associated with 1) a reduction of overall pore density accompanied by a 53% depression of glomerular filtration rate (GFR), and 2) appearance of a subset of large, nondiscriminatory pores, which accounted for the observed nephrotic level of proteinuria. Morphometric analysis of biopsy tissue provided evidence of reduced filtration surface area due to global or segmental occlusion of capillary loops in glomerular tufts. Activity of DPLN resolved posttreatment. A computed increase in pore density was associated with a 24% increment in GFR; a marked reduction in the fraction of shuntlike pores was accompanied by a parallel reduction of proteinuria into a subnephrotic range. Repeat biopsy revealed diminished glomerular cellularity, fewer immune deposits, and an ensuing increase in the fraction of tuft area occupied by patent loops. Epithelial filtration slit frequency also increased. Neither functional nor structural recovery was complete, however. Residual pore density approximated only 23-35% of that in healthy controls, and corresponding shuntlike pores were threefold more prominent. We conclude that severe DPLN is only partially reversible by current modalities of treatment and that the ensuing residual injury is far more severe than suggested by conventional tests of renal function.
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PMID:Extent of glomerular injury in active and resolving lupus nephritis: a theoretical analysis. 203 58

This report examines the correlation between glomerular injury and glomerular dysfunction in murine lupus nephritis. Glomerular filtration rate was measured by the clearance of inulin in conscious NZB/W female mice and shown to vary 12-fold in the animals tested. Detailed morphometric measurements were made on the perfused fixed kidneys. As disease progressed the surface density (Sv) of the open capillary loops decreased by 73%. This drop in Sv correlated with a 4-fold increase in mean glomerular volume (MGV, r = -0.79, p less than 0.0001). The "compensating" increase in MGV maintained or increased filtration surface area despite the loss of some capillary loops to proliferating and/or infiltrating cells. Filtration slit length/glomerulus and the filtration slit number/micron glomerular basement membrane varied 10-fold and were found to correlate directly with glomerular filtration rate (r = 0.64, p less than 0.0007 and r = 0.70, p less than 0.0001, respectively). When linear and multiple regression analyses were applied, all other structural measures, including filtration surface area, correlated with glomerular filtration rate poorly if at all. Glomerular permselective dysfunction (proteinuria) was measured as the fractional clearance of albumin (fractional clearance of albumin) and of IgG. Stepwise multiple regression analysis revealed the percentage of the glomerular basement membrane occupied by dense deposits, slit number/glomerular basement membrane, and glomerular basement membrane thickness statistically explained most (81%) of the variation in fractional clearance of albumin and IgG. These results suggest that epithelial slit length is the most important structural determinant of GFR and that the increase in MGV maintains filtration surface area despite evidence of an extensive inflammatory insult. The mechanism(s) of proteinuria in this model of lupus nephritis are consistent with either a focal increase in GBM permeability due to immune deposits and/or a diffuse increase in permeability due to GBM charge neutralization. The study provides insight as to why previous structure-function reports failed to find correlates of glomerular injury to glomerular dysfunction.
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PMID:Murine lupus nephritis. A structure-function study. 207 65

In this study we evaluated the incidence of chronic renal failure in children with asymptomatic proteinuria and/or hematuria detected by a mass screening program in school and kindergarten. A total of four thousand and three children, aged from 2 to 18 years old was referred to our institute between 1977 and 1990. Of them, 4 cases were AGN, 8 cases Alports' syndrome, 7 cases FGN, 7 cases F(s)GS, 3 cases HSPN, 148 cases IgA nephropathy, 12 cases MN, 24 cases MPGN (including 7 cases of focal type MPGN), 1 case lupus nephritis, and others. Of these children 2 of 8 cases of Alports' syndrome, one of 7 cases of FGS, 6 of 148 cases of IgA nephropathy and none of 24 cases of MPGN developed chronic renal failure. It is true that the incidence of chronic renal failure in children with various kinds of renal disease detected by a mass screening program is lower than that of symptomatic children. However, since we do not have yet any specific treatment in most cases and also since the follow-up period is not long enough, the definite conclusion that a mass screening program can alter the prognosis of children with renal diseases cannot be drawn except for some particular lesions such as MPGN, especially the focal type. Further study including a much larger population of patients is necessary.
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PMID:Screening for proteinuria and hematuria in school children--is it possible to reduce the incidence of chronic renal failure in children and adolescents? 208 74

We studied retrospectively 12 children with lupus nephritis divided in two groups according to the treatment made. The patients in the first group received oral 6-methyl-prednisolone alone, until children in the second received too oral cyclophosphamide. At the moment of the admission, no statistical differences were seen between both groups in terms of age, sex, clinical features, renal function, laboratory values and renal pathology based on the classification of the World Health Organisation. Patients in the second group showed a significantly better evolution in mortality (p less than 0.05), improvement of proteinuria and glomerular filtration rate (p less than 0.01 and p less than 0.05 respectively) and laboratory values, without important adverse effects. It seems that the addition of cyclophosphamide in the treatment of patients with lupus nephritis is useful to improve the prognosis of the illness in our patients.
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PMID:[Lupus nephropathy in children. Based on the authors' caseload]. 209 59

Serum levels of 6 anti-DNA antibody idiotypes were measured in 65 consecutive patients with systemic lupus erythematosus (SLE) and 45 healthy subjects. Five of the 6 idiotypes were elevated in SLE sera compared to the normal controls (p less than 0.005). Analysis of the associations of the idiotypes with clinical, hematological, and serological characteristics revealed that significantly decreased serum levels of 3 idiotypes (103.1, 100, and 1305) were associated with nephritis and that one of these idiotypes (103.1) was also associated with discoid rash. An association of lowered levels of 3 idiotype markers (604, 1305, and 1400) was also observed with the presence of lupus anticoagulant and anticardiolipin antibodies. Serial studies in individual patients with SLE nephritis failed to show a close correlation of serum idiotype levels with the degree of proteinuria, creatinine clearance, anti-DNA antibody, or complement values. The association of decreased levels of specific idiotypes with the presence of nephritis, discoid rash, and antiphospholipid antibodies suggests the participation of these antibodies in the pathogenesis of disease.
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PMID:Association of anti-DNA idiotype markers with clinical and serological manifestations in patients with systemic lupus erythematosus. 210 45


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