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)

In order to evaluate the pathogenesis of proteinuria and the charge of immune deposits in lupus nephritis, anionic sites of periodate-lysin-paraformaldehyde (PLP) fixed renal tissue (5 patients with renal pelvic tumor as normal control and 17 patients with lupus nephritis), were stained with the critical electrolyte concentration method. Cuprolinic blue (CB) was used as a cationic probe. Ultra-structural study and semi-quantitative analysis were done. In the normal glomerular basement membrane (GBM), the CB stainable anionic sites appeared as filamentous structure with several short lateral branches. On the basis of electron microscopic observation of isolated proteoglycan, it is suggested that the central filaments are the protein core and the branches are the glycosaminoglycans of proteoglycan molecules. These filamentous anionic sites were located mainly in the laminae larae and lie close to each other forming a mesh-like network pattern. The semi-quantitative analysis of the normal GBM revealed that the number of anionic sites in the lamina rara externa (LRE) was 22.9 +/- 1.9-23.7 +/- 1.4/1000 nm GBM and in the lamina rara interna (LRI) 14.0 +/- 1.6-15.1 +/- 1.5/1000 nm GBM. These findings suggest that the anionic sites composed of heparan sulphate proteoglycan occupy large area of the laminae larae and prevent permeation of anionic molecules. In non-proteinuric 5 patients with class II lupus nephritis, the number of anionic sites of the GBM (LRE; 21.3 +/- 2.0-22.3 +/- 1.8/1000 nm GBM, LRI; 13.5 +/- 2.0-14.2 +/- 2.0/1000 nm GBM) showed no significant difference from that of the normal GBM. In contrast, the GBM of proteinuric patients with class IV (6 patients, LRE; 14.8 +/- 2.7-19.3 +/- 1.8/aooo nm GBM, LRI; 5.8 +/- 1.9-11.3 +/- 2.4/1000 nm GBM) and (V) (6 patients, LRE; 13.0 +/- 2.4-17.9 +/- 2.8/1000 nm GBM, LRI; 12.0 +/- 1.9-13.0 +/- 2.5/1000 nm GBM) exhibited loss of the anionic sites in association with the localization of the immune deposits (ID). From these findings, it is concluded that in severe and active lupus nephritis the failure of charge barrier of the GBM is responsible for the proteinuria. The ID observed in the patients with lupus nephritis were not stained with CB. This finding suggests that net charge of the ID could be cationic and that cationic immune complex and/or antibody could involve in the pathogenesis of lupus nephritis.
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PMID:[Electron microscopic study of the glomerular basement membrane charge barrier and the charge of immune deposits in lupus nephritis]. 178 70

In experimental membranous nephropathy, antibody binding to glomerular epithelial cell membrane antigens results in complement activation and formation of complement C5b-9 membrane attack complexes in glomeruli. During active disease, the C5b-9 complexes are shed into the urine. To test the hypothesis that a similar mechanism might be operative in human membranous nephropathy, we measured urinary excretion of C5b-9 and C5 in 146 proteinuric patients with biopsy-proven glomerular diseases or diabetes mellitus. Urinary excretion of C5b-9 relative to C5 excretion was higher in 40 patients with membranous nephropathy than in 106 patients with proteinuria due to non-membranous glomerulonephritis when analyzed by covariance analysis (P less than 0.0002). Urinary C5b-9 excretion was higher in membranous nephropathy than in membranoproliferative glomerulonephritis (N = 13, P less than 0.05), minimal change-focal sclerosis (N = 33, P less than 0.001), mesangial proliferative glomerulonephritis (N = 9, P less than 0.02) and IgA nephropathy (N = 7, P less than 0.025). Urinary C5b-9 excretion was also higher in patients with lupus nephritis (N = 18, P less than 0.02) compared to those with non-membranous glomerulonephritis. The lupus patients with the highest excretion had clinical or pathological features of membranous nephropathy. Nine patients with membranous nephropathy and elevated urinary C5b-9 excretion had a shorter duration of disease (P less than 0.05), lower serum creatinine levels (P less than 0.05) and more proteinuria (P less than 0.02) than the 31 membranous nephropathy patients with normal values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevated urinary excretion of the C5b-9 complex in membranous nephropathy. 178 50

We have investigated the contribution to the autoimmune disease of (NZB x NZW)F1 (NZB/W) mice made by the T cell receptor beta (TcR beta) chain gene complex, or genes linked to it, that are derived from the NZW strain. For this we developed the NZW.TcR beta NZB strain, a NZW congenic line carrying the TcR beta of NZB type, and produced NZB x NZW.TcR beta NZB (NZB/W.TcR beta NZB)F1 mice. We compared the amounts of anti-DNA and anti-histone antibodies and also the severity of lupus nephritis in these mice with those in the original NZB/W F1 mice. We obtained evidence for significantly lower serum levels of autoantibodies to double-stranded and single-stranded DNA and histone, and a later onset and a lower incidence of proteinuria in the NZB/W.TcR beta NZB F1 mice than in the original NZB/W F1 mice. These findings clearly indicate that the gene(s) within or closely linked to the TcR beta chain gene complex on chromosome 6 of the NZW strain acts to intensify the feature of systemic lupus erythematosus in the NZB/W F1 strain. The significant relationship of this finding to the strict dependency of NZB/W F1 disease on the H-2d/H-2z heterozygosity is discussed.
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PMID:Contribution of the gene linked to the T cell receptor beta chain gene complex of NZW mice to the autoimmunity of (NZB x NZW)F1 mice. 182 67

We investigated the effects of YM-13650, 2-(m-carboxyacetoxyphenyl) imidazo [2, 1-b] benzothiazole, on BSA-immune complex nephritis in rats and lupus nephritis in NZB/W F1 mice. In preventative experiments on immune complex nephritis in rats, YM-13650 (10 approximately 100 mg/kg, p.o.) dose-dependently inhibited the increase in urinary protein, serum cholesterol, and urea nitrogen. Histopathological observation showed striking hypercellularity and mesangial widening in nephritic control; however, glomerular injury was reduced in YM-13650-treated animals. In therapeutic study, control rats maintained high levels of urinary protein, serum cholesterol and urea nitrogen throughout the experimental period. These variables were lower in YM-13650-treated rats. In preventative experiments in lupus mice treated from 8 weeks of age, YM-13650 in comparison with the control group showed a lesser degree of proteinuria throughout the experimental period. It also significantly prolonged or tended to prolong the life span of NZB/W F1 mice compared with the control. In therapeutic experiments conducted after the onset of lupus nephritis in mice, the drug also inhibited an increase in urinary protein and tended to prolong the life span. These results show that YM-13650 has preventative and therapeutic effects on experimental nephritis in rats and mice, and it may prove valuable as an anti-nephritic drug.
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PMID:[Effects of YM-13650 on experimental nephritis in rats and mice]. 183 34

Two-hundred and sixty-five patients with asymptomatic proteinuria and/or haematuria were studied at the Department of Medicine, Universiti Kebangsaan Malaysia and Department of Nephrology, General Hospital Kuala Lumpur. They represented 25.4% of all the renal biopsies performed during the period 1980-88. All the three races were affected with 71.3% occurring between the ages of 20-39 years and 41.1% were detected during routine medical examination. Excluding those patients with lupus nephritis, IgA nephropathy was the commonest histological diagnosis (51.7%). The presence of severe and advanced histological changes in a significant number of biopsies emphasises the need for more effective screening and early referral of this group of patients.
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PMID:Asymptomatic proteinuria and/or haematuria in 265 Malaysian adults. 183 19

We analysed the outcome of pregnancy in patients with pre-existing lupus nephritis, seen in a tertiary referral centre for nephrology. Fifty-three pregnancies in 25 patients who already had clinical and histological evidence of lupus nephritis were recorded between January 1970 and June 1989, and data were analysed retrospectively. All 53 pregnancies occurred in patients with more or less stable disease, while three pregnancies during which lupus first presented were excluded. Six pregnancies were ended by therapeutic abortions (four for social reasons), and in eight spontaneous abortion occurred. Thus, 39 deliveries occurred, 28 at 36 weeks or more, while 11 were delivered prematurely, of which one was a stillbirth. After allowance was made for therapeutic abortions, the fetal loss rate (9/47) was 19%. Seventeen Caesarian sections were performed in the 39 completed pregnancies (44%), 11 as emergencies. Although the overall fetal loss, incidence of premature births and Caesarian section rate were all higher than expected for a population of normal women, neither initial histology, treated hypertension, the presence of proteinuria or a nephrotic syndrome showed statistically significant relationships with the outcome of completed pregnancies. In no case was maternal renal function affected irreversibly, although proteinuria increased substantially during pregnancy in six patients, and creatinine clearance fell during pregnancy, also in six patients. No 'flares' in systemic disease were seen, but all patients save five were treated with a brief period of high-dose oral corticosteroids or intravenous methylprednisolone in the postpartum period. No case of neonatal lupus or congenital heart block was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The outcome of pregnancy in women with lupus nephritis. 184 58

Using an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI) = 84% +/- 52.8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI = 45% +/- 35.9). Seventy normal human sera had a mean BI of 10% +/- 9.8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (P less than 0.001). AECA levels correlated with low complement levels but not with anti-DNA antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0.68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role of these antibodies as a marker in lupus nephritis is discussed.
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PMID:Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis. 186 5

Idiotypes (Id) of human anti-DNA antibodies, designated as O-81 Id, were specifically detected on the immune deposits of renal glomeruli in 46% of patients with lupus nephritis. Id-binding to anti-Id antibodies was blocked by free O-81 Id and to some extent by free DNA. DNase or acid buffer treatment failed to reveal new Id determinants on the deposits. O-81 Id and NE-1 Id activity were also detected on the renal eluate-derived IgG, but not IgM from the autopsy cases with lupus nephritis. The incidences of O-81 Id were not associated with histological features in the glomeruli, but the distribution patterns were similar to those of IgG deposits. Our study also showed that 65% to 70% of patients with IgG deposits either in the subendothelium or in the subepithelial area of the glomerular basement membrane (GBM) showed positive tests for O-81 Id. It was also noted that most patients with massive proteinuria had O-81 Id in their glomeruli. It is concluded that O-81 Id deposits are relatively specific for active lupus nephritis and that immunofluorescence studies using anti-Id antibodies may be clinically useful for specifying the renal lesions of systemic lupus erythematosus (SLE).
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PMID:Anti-DNA idiotypes deposited in renal glomeruli of patients with lupus nephritis. 186 80

In order to study the role of active oxygen radicals on the progression of the immune-complex (IC) nephritis, we administered superoxide dismutase (SOD), catalase (CAT), and dimethylthiourea (DMTU) to (NZB x NZW) F1 mice from 8 weeks of age, 3 times a week. At 40 weeks of age, the urine protein of the control (n = 23) was 11.4 +/- 4.1 mg/day. SOD (n = 12), CAT (n = 6) and SOD + CAT (n = 5) groups were 1.5 +/- 0.4, 25.4 +/- 14.7, 0.7 +/- 0.1 mg/day, respectively. DMTU group (n = 12) showed significantly less proteinuria (0.6 +/- 0.1 mg/day, p less than 0.05) than control. Even if the injection was begun from the late stage of the disease, some effect was observed. Moreover, by DMTU, urinary excretion ratio of PGF1 alpha/TXB2 0.025 +/- 0.003 was higher than control 0.015 +/- 0.001 (p less than 0.05). These findings suggest that oxygen radicals may play an important role during the progression of lupus nephritis. Among the oxygen radical species, hydroxyl radical is considered to be the most pathogenetic factor in IC-mediated nephritis.
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PMID:[Role of active oxygen on the progression of murine lupus nephritis]. 190 63

Omega-3 polyunsaturated fatty acids are among new treatments being tested for efficacy in immune renal disease. The principal omega-3 polyunsaturated fatty acids are eicosapentaenoic acid and docosahexaenoic acid. They are derived from alpha-linolenic acid, which is found mainly in marine lipids. Eicosapentaenoic acid and docosahexaenoic acid undergo biologic transformation into trienoic eicosanoids that alter inflammatory mediators and vascular reactivity, both of which are important in the pathogenesis of certain glomerular immune diseases. Investigators have shown that proteinuria was prevented and survival was prolonged in autoimmune models of nephritis after dietary supplementation with fish oil. Furthermore, vascular damage may be modified by the influence of eicosapentaenoic acid and docosahexaenoic acid on blood rheology, aggregation of platelets, and plasma lipids. In short-term clinical studies, omega-3 polyunsaturated fatty acids seem to diminish cyclosporine-induced nephrotoxicity and the attendant complication of hypertension, to inhibit inflammatory and atherogenic mechanisms in lupus nephritis, and to preserve renal function and reduce proteinuria in IgA nephropathy. Long-term clinical trials for testing fish oil in these three clinical conditions are under way to confirm or refute these apparent beneficial therapeutic results.
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PMID:Omega-3 polyunsaturated fatty acids: a potential new treatment of immune renal disease. 192 84


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