UMLS:C0033687 - FACTA Search

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Query: UMLS:C0033687 (proteinuria)
24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic lupus erythematosus (SLE)-prone female MRL-lpr / lpr (MRL-lpr) mice were treated with mouse or rat IFN-gamma under different experimental conditions, both prophylactically in 6- to 8 week-old animals and therapeutically in 12- to 18-week-old SLE-affected mice. It was found that IFN-gamma heterogeneously modulated the course of the disease in MRL-lpr mice. When administered prophylactically, IFN-gamma favorably modulated the histological, serological and clinical signs of the disease. Relative to untreated or PBS-treated control animals, the MRL-lpr mice which received IFN gamma were virtually free of inflammatory infiltration of the kidneys and the lungs, had lower levels of azotemia with reduction of both circulating IgG1, IgG2a and IgG3 and anti-double strand (ds) and single strand (ss) DNA antibodies, milder skin vasculitis, significantly reduced enlargement of their lymph nodes and lower weight of the spleens. IFN-gamma also lowered the rate of mortality of MRL-lpr mice. In contrast to these findings, therapeutically administered IFN-gamma worsened the course of the disease in MRL-lpr mice, which exhibited increased proteinuria, higher levels of IgG2a and IgG3 and anti-ds and -ss DNA antibodies, more aggressive nephritis and died at an earlier age than PBS-treated control mice. The dichotomic effect of IFN-gamma on disease manifestation in MRL-lpr mice offers new insights into the complex role of this cytokine in the regulation of systemic autoimmunity such as SLE.
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PMID:Dichotomic effects of IFN-gamma on the development of systemic lupus erythematosus-like syndrome in MRL-lpr / lpr mice. 1067 Nov 99

Thirty years of clinical studies have shown that a correct therapeutic approach to human glomerulonephritides with nephrotic syndrome requests the evaluation of three important parameters such as renal biopsy, long monitoring of daily proteinuria and renal function. In addition, age and clinical manifestations should be considered. Corticosteroids, alkylating agents (cyclophosphamide, chlorambucil) and purine analogues are currently used in the treatment of primary glomerulonephritis (minimal-change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous (MGN) and membranoproliferative glomerulonephritis (MPGN)), however results are different. Patients with nephrotic syndrome in MCD when treated with corticosteroids and/or cytotoxic drugs have complete or partial remission in a more than 90% of cases. On the contrary, nephrotic FSGS remits completely or partially only in 50% of treated cases when a more aggressive and prolonged immunosuppressive therapy is carried out. Data from clinical trials in MGN patients are controversial, however it is evident that a greater percentage of patients with stage 1 and stage 2 renal lesions benefit from corticosteroids in association with immunosuppressive drugs. Finally, no encouraging data have been obtained by clinically controlled trials in patients with MPGN. Future perspectives suggest the use of other drugs such as receptor blockade of cytokines and growth factors, administration of cytokine antagonists, intracellular signalling blockade and gene therapy with antisense oligonucleotides. Unfortunately, until specific therapies become available, we have to use unspecific or only symptomatic therapy.
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PMID:Primary glomerulonephritides with nephrotic syndrome. Limitations of therapy in adult patients. 1068 12

Macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory cytokine that also counter-regulates glucocorticoid action. We investigated whether immunoneutralization of MIF could reverse established experimental crescentic glomerulonephritis and if this treatment could modulate endogenous glucocorticoid levels. Accelerated anti-GBM glomerulonephritis was induced in six littermate pairs of rats. Once crescentic disease was established on day 7, one animal in each pair was given a daily injection of neutralizing anti-MIF antibody (Ab) or irrelevant isotype control Ab for 14 days and then killed on day 21. In addition, a group of 6 animals was killed on day 7 of disease without any treatment. Animals receiving the control Ab exhibited a rapidly progressive glomerulonephritis with severe renal injury (proteinuria), loss of renal function (creatinine clearance), anemia, and marked histologic damage (including glomerular crescent formation), compared with animals killed on day 7 without treatment. In contrast, anti-MIF Ab treatment partially reversed the disease by restoring normal renal function and reducing histological damage compared with untreated animals killed on day 7 (p < 0.05). Interestingly, anti-MIF Ab treatment also prevented severe anemia (p < 0.05). Reversal of disease was associated with a significant reduction in leukocyte infiltration and activation and renal interleukin-1 (IL-1) production. Importantly, anti-MIF Ab treatment caused a significant increase in endogenous serum corticosterone levels, which correlated with the reversal of disease parameters. In conclusion, this study has demonstrated that blocking MIF activity can partially reverse established crescentic glomerulonephritis and suggests that MIF operates by both enhancing the cellular immune response and suppressing the endogenous anti-inflammatory glucocorticoid response.
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PMID:Reversal of established rat crescentic glomerulonephritis by blockade of macrophage migration inhibitory factor (MIF): potential role of MIF in regulating glucocorticoid production. 1078 Aug 84

Previous study suggested that MRL-lpr/lpr mice treated with tamoxifen (TAM) had less severe proteinuria, reduced serum titre of anti-dsDNA autoantibodies and an increased survival rate. To investigate further the regulatory mechanisms of TAM on MRL-lpr/lpr female mice, a total dose of 200 microg per mice (5.5 mg/kg) was given every 2 weeks subcutaneously, while the control mice were injected with oil only. After being treated with TAM four times, the mice were killed and cellular functions were evaluated. The TAM-treated groups had smaller sized spleen and lymph nodes. Flow cytometric analysis of splenocytes had a significantly lower percentage of cell number of T cells and double negative T cells (CD4- CD8- T cells). There was no difference in cytokine production (interleukin (IL)-2, IL-4, IL-5, IL-10 and interferon-gamma (IFN-gamma)) from splenocytes stimulated with concanavalin A (Con A) or cytokines (IL-6) secreted by peritoneal exudate cells when stimulated with lipopolysaccharide (LPS). However, IL-2 from lymph node cells was significantly higher on TAM-treated mice. Finally, splenocytes or purified T cells stimulated with anti-CD3 antibody plus cross-linking immunoglobulin G (IgG) of the TAM-treated group had higher 3H-incorporation of proliferation assay compared with that of control groups. In vitro study further demonstrated that IL-2-activated proliferation of lymph node double negative (DN) T cells can be inhibited by TAM treatment in a dose-dependent manner. Our finding demonstrated that TAM may potentially influence T cells and modulate the immune function, which offers a novel approach to explore the feasibility of hormone therapy for autoimmune diseases.
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PMID:Tamoxifen alleviates disease severity and decreases double negative T cells in autoimmune MRL-lpr/lpr mice. 1080 66

Glomerular expression of cytokines, interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha), together with leukocytic infiltration, are prominent features in crescentic glomerulonephritis. Because these cytokines are targets for nuclear transcription factor-kappaB (NF-kappaB), the use of NF-kappaB decoy oligodeoxynucleotide (ODN) treatment was evaluated in an experimental disease model. Crescentic glomerulonephritis was induced in primed Wistar rats by injection of sheep antiglomerular basement membrane serum. Thirty minutes after injection, rats were anesthetized and the left kidney was perfused with NF-kappaB decoy ODN or scrambled ODN control mixed with a virus-liposome complex, and then killed 7 d later. Animals given the scrambled control ODN developed severe glomerulonephritis by day 7 with heavy proteinuria, glomerular crescents and interstitial lesions, marked leukocytic infiltration, and upregulated renal expression of cytokines (IL-1 and TNF-alpha) and adhesion molecules (intercellular adhesion molecule-1). In contrast, NF-kappaB decoy ODN treatment substantially inhibited the disease with a 50% reduction in proteinuria, a threefold reduction in histologic damage, a 50% reduction in leukocytic infiltration, and a 50 to 80% reduction in the renal expression of cytokines and leukocyte adhesion molecules. In conclusion, this study has demonstrated that NF-kappaB plays a key role in cytokine-mediated renal injury and that NF-kappaB decoy ODN treatment has clear therapeutic potential in rapidly progressive glomerulonephritis.
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PMID:In vivo administration of a nuclear transcription factor-kappaB decoy suppresses experimental crescentic glomerulonephritis. 1086 80

Systemic lupus erythematosus (SLE) is characterized by immune abnormalities explained by the overproduction of Th(2)cytokines such as autoantibody production and polyclonal B cell activation. We examined the effect of administering a DNA plasmid encoding IL-12 on the lupus-like disease of MRL/MP-lpr/lpr (MRL/lpr) mice. Treatments were delivered intramuscularly every 4 weeks, starting at 4 weeks of age. This intervention significantly inhibited the accumulation of CD4(-)CD8(-)T cells, and reduced lymphadenopathy and splenomegaly. A significant decrease in serum IgG anti-DNA autoantibody titers was observed, and plasmid IL-12 therapy was also associated with a reduction in the proteinuria and glomerulonephritis characteristic of this disease. Serum IFN-gamma level was increased by inoculating IL-12 encoding plasmid, suggesting that the cytokine balance was skewed towards Th(1). The clinical implications of this suppression of autoimmune disease are also discussed.
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PMID:IL-12-encoding plasmid has a beneficial effect on spontaneous autoimmune disease in MRL/MP-lpr/lpr mice. 1088 Feb 49

Small amounts of amyloid in kidney biopsy specimens may be missed on routine examination unless specifically targeted. Occasionally, this oversight results in a diagnosis of minimal change glomerulonephritis (MCGN). This misdiagnosis may be facilitated by the fact that typical "minimal changes" with flattening and effacement of the epithelial foot processes can be found in capillary loops directly affected by amyloid deposition as well as in capillary loops of glomeruli with only mild amyloid deposition in the mesangium. Repeatedly, the diagnosis of MCGN had to be corrected to renal amyloidosis when re-examination by special techniques succeeded in detecting even small amounts of amyloid fibrils. We present the case of a previously healthy 49-year-old man who suddenly developed nephrotic syndrome. A first renal biopsy showed MCGN. Proteinuria remained refractory to immunosuppressive treatments, and creatinine clearance deteriorated rapidly. Two years later, a repeat renal biopsy showed AL-amyloidosis. In this case, re-examination of the first biopsy in the light of the final diagnosis again did not show any deposition of amyloid fibrils. We suspect that proteinuria and epithelial podocyte changes in amyloidosis are caused by factors other than deposition of amyloid fibrils itself. Possibly a cytokine release during the early fibril formation leads to abnormalities even before the typical structural changes of renal amyloidosis can be detected. This is analogous to the hypothesis of a circulating factor that leads to proteinuria in focal segmental glomerulosclerosis or the speculation of altered lymphokine expression associated with the development of MCGN in Hodgkin's disease.
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PMID:AL-amyloidosis of the kidney initially presenting as minimal change glomerulonephritis. 1097 97

It has been documented that sex hormone may play a role in the pathogenesis of murine lupus. To determine the effect of tamoxifen (TAM) on NZB/W F1 female mice, a total dose of 800 microg (22 mg/kg body weight) of TAM was administered subcutaneously every 2 weeks. The control mice were injected with peanut oil only. After treatment with TAM for 5 months, the mice were killed and immunological parameters were evaluated. The results suggest that NZB/W F1 mice treated with TAM had less severe proteinuria and increased survival rate compared to controls. Flow cytometric analysis of splenocytes revealed a significantly lower percentage of B cells and CD5+ B cells in the TAM-treated group. There was a significantly lower serum level of soluble tumour necrosis factor (TNF) receptor I and II molecules in the TAM-treated mice. Immunohistological study showed that control mice had severe immune complex deposition in the kidney. In contrast, TAM-treated mice had much less pathological change. In summary, this study demonstrated that TAM treatment might be able to alleviate the symptoms of lupus nephritis, influence B-cell count, modulate the expression of cytokine receptors and thereby subsequently affect immune function. Further studies to determine the cellular mechanisms in lupus nephritis may increase our understanding of this complex disease and provide additional targets for therapeutic intervention.
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PMID:Tamoxifen decreases renal inflammation and alleviates disease severity in autoimmune NZB/W F1 mice. 1101 11

The role of ANG II on renal and cardiac gene expression of matrix proteins was studied in rats with progressive renal disease. Induction of renal failure by five-sixths nephrectomy of Sprague-Dawley rats resulted in hypertension (163 +/- 19 vs. control pressures of 108 +/- 6 mmHg), proteinuria (83 +/- 47 vs. 14 +/- 2 mg/day), and increased renal expression of fibronectin, thrombospondin, collagen I and III, transforming growth factor-beta (TGF-beta), and plasminogen activator inhibitor-1 (PAI-1) mRNA. Treatment with the ANG II receptor antagonist, eprosartan (60 mg. kg(-1).day(-1)), lowered blood pressure (95 +/- 5 mmHg) and proteinuria (19 +/- 8 mg/d) and abrogated the increased TGF-beta, fibronectin, thrombospondin, collagens I and III, and PAI-1 mRNA expression. An increase in left ventricular weight was observed in five-sixths nephrectomized rats (0.13 +/- 0.01 vs. 0.08 +/- 0.01 g/100 g body wt), a response that was inhibited by eprosartan treatment (0.10 +/- 0.01 g/100 g). Left ventricular expression of TGF-beta and fibronectin was also increased in rats with renal disease; however, the small decreases in expression observed in eprosartan-treated rats did not reach statistical significance. These data suggest that eprosartan may be beneficial in progressive renal disease and that the mechanism of action includes inhibition of cytokine production in addition to antihypertensive activity.
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PMID:Gene expression in rats with renal disease treated with the angiotensin II receptor antagonist, eprosartan. 1107 11

MHC II and CD4+ T cells are required for anti-glomerular basement membrane (GBM) globulin-initiated crescentic glomerulonephritis (GN) in mice, but the role of MHC I and CD8+ T cells is unclear. The cytolytic function of CD8+ T cells requires recognition of peptide antigens presented on MHC I. CD8+ T cells can also perform helper functions via cytokine production. The contribution of MHC I to crescentic GN was investigated using TAP-1 gene knock out (TAP-1-/-) mice, which have deficient MHC I antigen presentation. Heterozygous TAP-1 mice have normal MHC I expression and developed GN with crescents in 42 +/- 4% of glomeruli (normal 0%), proteinuria (9.1 +/- 1.6 mg/20 h, normal 1.5 +/- 0.3 mg/20 h) and impaired renal function (creatinine clearance 110 +/- 8 microl/min, normal 193 +/- 10 microl/min) following administration of sheep anti-mouse GBM globulin. TAP-1-/- mice, which have extremely low MHC I expression and reduced CD8+ T cells, developed similar GN with 39 +/- 3% crescents, proteinuria (12.7 +/- 4.3 mg/20 h) and impaired renal function (creatinine clearance 123 +/- 20 microl/min). In vivo antibody-induced CD8 depletion did not attenuate crescent formation or protect renal function in C57Bl/6 mice developing GN, although significant reduction in proteinuria (5.3 +/- 1.2 mg/20 h, P = 0. 012) and glomerular recruitment of CD4+ T cells and macrophages were observed compared with control treated mice with GN. These data demonstrate that MHC I is not required for development of crescentic GN in mice. The MHC I-independent contribution of CD8+ T cells to proteinuria and inflammatory cell recruitment suggests that they may serve a 'helper' rather than cytolytic role in this disease.
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PMID:MHC class I pathway is not required for the development of crescentic glomerulonephritis in mice. 1112 54

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