Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To date no specific serological parameter is available to assess disease activity in SLE. Soluble serum thrombomodulin is a new marker of endothelial cell injury and vasculitis. The objective of this study was to compare in vivo soluble thrombomodulin as marker of disease activity in SLE with established and recent serological parameters. One hundred and twenty-four sera of 30 patients with proven SLE with different disease activities were tested for serum levels of thrombomodulin, intercellular adhesion molecule-1 (ICAM-1), E-selectin, vascular cell adhesion molecule-1 (VCAM-1), IL-2R, IL-6, IL-10, dsDNA by ELISA and dsDNA additionally by radioimmunoassay (RIA). C-reactive protein (CRP), complement component C3, IgG, creatinine, anti-nuclear antibodies (ANA) and intermediate filament antibodies were measured by standard laboratory tests. The clinical disease activity was evaluated by the Systemic Lupus Activity Measure (SLAM). Correlations of the different serological SLE disease activity parameters with the SLAM scores revealed the highest significance for serum thrombomodulin (correlation coefficient 0.82). This was further confirmed by the intra-individual analysis of follow-up sera. In addition, a moderate correlation could be found for IL-6, IL-10, ICAM-1, CRP and erythrocyte sedimentation rate (ESR). In summary, soluble thrombomodulin is the most important serological parameter of disease activity in SLE currently available, as shown by the in vivo studies. Soluble thrombomodulin might be a valuable serological parameter for therapeutical considerations.
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PMID:Serum thrombomodulin-a reliable marker of disease activity in systemic lupus erythematosus (SLE): advantage over established serological parameters to indicate disease activity. 1060 82

The severity of renal disease in systemic lupus erythematosus is variable. Renal biopsy is important to guide the treatment. The World Health Organization classification define six different histological categories with possible transformations from one category to another. Histological signs of activity or chronicity are important with respect to prognosis and treatment. Examination of renal biopsy allows predicting the reversibility of histological lesions following therapy. Apart from histological signs of severity, other factors may influence the prognosis: arterial hypertension, initial serum creatinine, the delay between onset of renal disease and treatment, the occurrence of exacerbations of the nephropathy, and the response to therapy by the end of the first year. The prognosis of severe forms of lupus nephritis, mainly diffuse proliferative glomerulonephritis, has improved during the last 20 years. The addition of immunosuppressive agents (cyclophosphamide, azathioprine) to corticosteroids is responsible for this improvement. Methylprednisolone pulses are as effective as oral high doses of prednisone during initial treatment and have fewer side effects. Many authors advocate monthly cyclophosphamide pulses over six months, sometimes followed by quarterly pulse cyclophosphamide. However, such an approach has not been proven to be more effective than an oral course of cyclophosphamide and/or azathioprine. On follow-up, steroid therapy should be slowly tapered, and close monitoring of lupus serological parameters (anti-DNA antibodies, complement), urinary protein excretion rate, urinary sediment and renal function allow one to detect exacerbations of the disease, which may require adapted therapy. While such protocols have improved the outcome, they have potential side effects. In addition to the deleterious effect of steroids on physical appearance, often badly tolerated by adolescents, immunosuppressive treatments increase the risks of severe infectious complications and the risks of cardiovascular complications in young adults.
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PMID:[Treatment of lupus nephritis in children]. 1062 4

To confirm the significance of excretion of annexin V into the urine and the change of urinary annexin V concentration in kidney disease, a sandwich enzyme-linked immunosorbent assay (ELISA) was developed using two monoclonal antibodies. Urinary annexin V concentration was measured in healthy individuals and patients with kidney and other diseases. Urinary annexin V did not change over a range of pH between 5.0 and 8.0, and was stable during the course of the study for 24 h at room temperature and for 8 days at 4 degrees C. The mean urinary annexin V concentration in 105 normal healthy individuals was 1.5+/-1.5 ng/ml, while that in patients with nephrotic syndrome and systemic lupus erythematosis (SLE) nephritis was 9.3+/-9.1 and 6.6+/-6.7 ng/ml, respectively, and that in IgA nephropathy and chronic renal failure was 2.6+/-2.1 and 1.3+/-0.7 ng/ml, respectively. Annexin level correlated with urinary protein concentration (r=0. 717), but not the serum creatinine concentration, blood urea nitrogen (BUN) and 24-h creatinine clearance. Mean urinary annexin V concentration in patients with ischemic heart disease, hypertension, and diabetes mellitus was 1.4+/-1.0, 1.4+/-1.1, and 1.7+/-1.3 ng/ml, respectively. In one case of relapsing nephrotic syndrome, the urinary annexin V concentration was markedly increased in the early phase after admission and then decreased. This patient later required hemodialysis. These results suggest that a high urinary annexin V concentration may be an indicator of acute renal injury related to the urinary protein level.
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PMID:Measurement of urinary annexin V by ELISA and its significance as a new urinary-marker of kidney disease. 1087 2

The outcomes of 32 lupus patients with rapidly progressive crescentic glomerulonephritis were studied. Lupus nephritis accounted for 51.6% (32/62) of all patients with biopsy proven rapidly progressive crescentic glomerulonephritis during a six year observation period that includes 961 consecutive native kidney biopsies. Median entry serum creatinine was 221 micromol/l. All patients received induction therapy with pulse methylprednisolone (n =27) or intravenous cyclophosphamide (n = 5). Maintenance therapies included prednisolone alone (group 1), prednisolone plus intermittent pulse intravenous cyclophosphamide (IVCY) (group 2) and prednisolone plus daily oral cytotoxic drugs (group 3). Twelve patients eventually had uremia. Seven further patients died of infection during therapy. One patient still had renal insufficiency and twelve patients had favorable clinical outcome (serum creatinine < 200 micromol/l). Patients in group 3 were more likely to have favorable clinical outcome than group 2 (P = 0.01; Fisher's exact test). Survival analysis found that the three year survival of 'group 2' was 27.6% while that of 'group 3' was 83.3%. Our results suggest that lupus nephritis is not an infrequent cause of crescentic glomerulonephritis. Therapy with IVCY is not necessary associated with good outcome. Selected patients can be effectively treated with daily oral cytotoxic drugs as a reasonable alternative therapy.
Lupus 2000
PMID:Lupus nephritis: a challenging cause of rapidly progressive crescentic glomerulonephritis. 1098 46

Individual case reports have documented nephrotoxicity of intravenous immunoglobulin (IVIG) preparations, but the true incidence of renal dysfunction is unknown and many data sheets do not include renal impairment as a side-effect of these preparations. We determined the incidence of renal impairment in an unselected cohort of patients receiving two different preparations of IVIG over 20 months, administering 287 courses of IVIG to 119 patients for a variety of indications, including thrombocytopenia, systemic lupus erythematosis, neuropathy, Guillain-Barre syndrome and infections. Two different preparations of IVIG were used, Vigam (BPL) and Sandoglobulin (Novartis), which differ in the concentration of sucrose added as a stabilizer. Eight patients showed deterioration in renal function (6.7%), and in two, no renal recovery occurred (1. 7%). There were no significant differences in the patient characteristics or dose or preparation of IVIG administered to those patients with or without changes in serum creatinine. There was no association between the amount of sucrose in the IVIG and development of renal failure. IVIG (regardless of the sucrose content) is associated with renal impairment which may be irreversible, with a maximum incidence of 6.7%. All patients should have their renal function monitored during the use of IVIG.
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PMID:Nephrotoxicity of intravenous immunoglobulin. 1107 32

Data related to the disease course of patients with systemic lupus erythematosus (SLE) with special attention to the persistence of disease activity in the long term are scarce. At this moment reliable figures are only known about the survival rate as a measure of outcome. The aim of this multicenter study was to describe the outcome of SLE patients with a disease duration of greater than 10 y. Outcome parameters were two disease activity-scoring systems (SLEDAI and ECLAM), the end organ damage (SLICC/ACR damage index) and treatment. Our results are derived from 187 SLE patients followed at 10 different centres in Europe over a period of 1 y. Serious clinical signs or exacerbations, defined by the occurrence or detoriation of already existing symptoms of renal and cerebral nervous systems were observed in 2-11% of the patients, seizures and psychosis in 3%, proteinuria in 11% and an increase in serum creatinine in 5% of the patients. No change took place in the overall damage index. Yet, the disease course in most patients was characterized by periods of tiredness (42-60%), arthritis (20-25%), skin involvement such as malar rash (32-40%), migraine (15-20%), anaemia (15%) and leucopenia (17-19%). Summarizing these results it is shown that patients, still under care after such a long time of having this disease, do have a disease that is far from extinguished.
Lupus 2001
PMID:Systemic lupus erythematosus. Disease outcome in patients with a disease duration of at least 10 years: second evaluation. 1124 10

The aim of this study was to assess the skeletal metabolism in a murine model of systemic lupus erythematosus (SLE). MRL/n and MRL/l mice (respectively representing a benign and a malignant form of the disease) were observed from 1.5 to 6.5 months of life. The monthly follow-up included: biochemical and histomorphometrical studies of the femoral bone, serum biochemistry, immunoglobulins and osteocalcin, and histological evaluation of the kidney tissue. The results showed a higher femoral weight (+11.5%), calcium (+4.4%) and protein bone content (+11.4%) and a significantly higher (+77%) phosphorus bone content in the MRL/n group; significantly lower (-48.9%) bone alkaline phosphatase enzymatic activity, lower bone alkaline/acid phosphatase enzymatic activities ratio (-40.8%) and lower (-38.4%) serum osteocalcin values in the MRL/l group (which might suggest reduced bone formation in these animals); markedly smaller trabecular bone volume (BV/TV) in the femoral head (-36.2%) and femoral neck (-39.8%), and smaller cortical and femoral areas in the mid-femoral shaft (-38.8% and -38.1% respectively) in the MRL/l group; higher serum immunoglobulins, increased serum blood urea nitrogen (BUN) and creatinine and a higher index of activity in the kidney histology in the MRL/l group, indicating increased activity of the disease in this substrain. The MRL mice, through their two substrains, may serve as a valuable laboratory animal model for study of the skeletal changes in SLE and of the influence of the disease activity on the skeletal metabolism.
Lupus 2001
PMID:Osteoporosis in murine systemic lupus erythematosus--a laboratory model. 1143 79

Antiphospholipid antibodies (aPL), especially lupus anticoagulant (LAC), characterize systemic lupus erythematosus (SLE) patients at increased risk for arterial and venous thromboembolic complications. It has been reported that purified human anti-phospholipid antibodies cause endothelial cell activation in in vitro experiments. In order to investigate whether increased endothelial cell activation is associated with thromboembolic events in SLE patients with LAC, we measured plasma levels of thrombomodulin (TM), von Willebrand factor (vWf), sP-selectin, vascular cell adhesion molecule-1 (sVCAM-1) and ED1-fibronectin in a study of 76 patients with SLE. Patients were subdivided on the basis of: no history of thrombosis and LAC-negative (n = 22) or LAC-positive (n = 17); positive history of thrombosis and LAC-negative (n = 16) or LAC-positive (n = 21). The median SLE disease activity index (SLEDAI) was 4. Although concentrations of sTM, vWf, sP-selectin and sVCAM-1 were significantly elevated in SLE compared with values in healthy controls, they did not differ between the four groups, between patients with or without history of thrombosis, and between patients with or without LAC. Presence of anticardiolipin antibodies could not explain these negative findings. Adjustment of the concentrations for significantly associated variables, such as age, hypertension, smoking, immunosuppressive treatment and concentrations of creatinine, cholesterol and homocysteine, did not change the main results of the study. Only sTM was significantly lower in patients with both LAC and thrombosis than in patients without both these features after adjustment for serum creatinine concentrations. In conclusion, we did not find an association between endothelial cell activation and presence of LAC or history of thrombosis in SLE.
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PMID:Lupus anticoagulant and history of thrombosis are not associated with persistent endothelial cell activation in systemic lupus erythematosus. 1147 38

Cyclophosphamide (CYC) has proven beneficial in preserving renal function in patients with lupus with diffuse proliferative glomerulonephritis (DPGN). However, the optimal route of CYC administration is unknown because direct comparative studies are unavailable. In this open study, we compared the renal outcome of two historical cohorts of patients with diffuse proliferative lupus nephritis (World Health Organization classes IVa and IVb) treated with either intravenous (IV) pulse CYC (group A; n = 22) or sequential oral CYC followed by azathioprine (AZA; group B; n = 21) and followed up prospectively. Both groups of patients had similar clinical, biochemical, and renal parameters at baseline. At 24 months posttreatment, significant improvements in proteinuria, creatinine clearance, serum albumin level, and lupus serological results were evident in both groups. Compared with patients in group A, patients in group B had more complete or partial remission (90% versus 73%) and less risk for treatment failure (5% versus 14%), renal flares (5% versus 14%), and doubling of creatinine levels (5% versus 9%), but the difference was not statistically significant. However, patients treated with oral immunosuppression had an insignificant increase in rates of herpes zoster infection (19% versus 9%) and menstrual disturbance (50% versus 29%). We conclude that sequential oral immunosuppression with CYC and AZA tended to have better efficacy than IV pulse CYC in the treatment of lupus DPGN but was associated with more toxicities. Additional randomized trials involving a larger cohort of patients with a longer period of observation are necessary.
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PMID:Treatment of diffuse proliferative lupus glomerulonephritis: a comparison of two cyclophosphamide-containing regimens. 1147 50

In the course of the antiphospholipid syndrome (APS), the existence of vaso-occlusive lesions capable of affecting numerous organs is now well established. The renal involvement attributable to primary APS, APS nephropathy (APSN), corresponds to vaso-occlusive lesions of the intrarenal vessels, associating side-by-side, acute thromboses with chronic arterial and arteriolar lesions, leading to zones of cortical ischemic atrophy. A retrospective study of 114 lupus patients undergoing renal biopsy was undertaken to determine the following: (1) if APSN can be found in the course of systemic lupus erythematosus (SLE); (2) if certain clinical and biologic factors can permit the prediction of the presence of APSN; and (3) if APSN is a superadded renal morbidity factor in lupus patients. This study shows the following: (1) APSN occurs in SLE (32% of patients with renal biopsies) in addition to, and independently of, lupus nephritis; (2) APSN is statistically associated with lupus anticoagulant but not with anticardiolipin antibodies; (3) APSN is associated with extrarenal APS, mainly arterial thromboses and obstetrical fetal loss, but not with the venous thromboses of APS; (4) APSN is an independent risk factor, over and above lupus nephritis, that contributes to an elevated prevalence of hypertension, elevated serum creatinine, and increased interstitial fibrosis. Thus, it seems likely that, because of its associations with hypertension, elevated serum creatinine, and increased interstitial fibrosis, APSN may worsen the prognosis in these patients. APSN may also have therapeutic significance in that its recognition should permit a better balance between immunosuppressor and antithrombotic and/or vasoprotective therapy. Finally, this study suggests that APSN should be considered as an element to be included in the classification criteria of APS.
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PMID:Antiphospholipid syndrome nephropathy in systemic lupus erythematosus. 1175 20


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