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)

This study aimed to define prognostic indicators of death in renal biopsies from Spanish patients with SLE. Renal biopsies of eighty-five lupus patients with and without clinical nephritis, taken between 1974 and 1987, were reviewed. Samples previously processed for light (LM), immunofluorescence (IM) and electron (EM) microscopy were analysed blind. Kaplan-Maier curves, log-rank test, and multivariate Cox's regression statistical methods were used for comparison of biopsy data in relation to patient survival. Univariate analysis showed that vascular hyalinosis, glomerular sclerosis, fibrous crescent and chronicity index higher than 3 by LM, and intramembranous dense-deposits by EM are predictors of poor survival. A multivariate approach confirmed the independent influence of vascular hyalinosis, chronicity index higher than 3 and intramembranous deposits. A predictive model can be constructed with three LM (hyalinosis, tubular atrophy and glomerular sclerosis) and three EM variables (subepithelial, mesangial and intramembranous deposits). Selected renal biopsy changes detected by LM and EM are therefore predictors of death in patients with lupus. Chronicity markers, more than those of activity or severity, are the best prognostic indicators.
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PMID:Light, immunofluorescence and electron microscopy renal biopsy findings as predictors of mortality in eighty-five Spanish patients with systemic lupus erythematosus. 815 89

Sera from 45 patients with lupus nephritis (LN), 63 patients with immunoglobulin A nephropathy (IgA N), and 71 glomerulonephritic controls (including 44 mesangial proliferative glomerulonephritis cases, 14 membranous glomerulonephritis cases, and 13 focal segmental glomerular sclerosis cases), and from 33 normal control subjects were tested by a cellular enzyme-linked immunoabsorbent assay for their anti-endothelial cell antibody (AECA) activity. Compared with normal controls, AECAs of the IgG subtype (AECA-IgG) were detected in LN (P < 0.001) and AECAs of the IgA subtype (AECA-IgA) were detected in both IgA N and LN (P = 0.018 and P < 0.001, respectively). Binding activity of AECA to endothelial cells was inhibited by endothelial cell lysate and fibroblast lysate but not by lymphocyte lysate, double stranded-DNA, or bovine serum albumin. Anti-endothelial cell antibody-positive sera also reacted with fibroblasts. In IgA N, associations were found between the presence of AECA and younger age (P = 0.036), proportion of crescents greater than 10% (P = 0.016), fibrin crescents (P = 0.016), and focal and segmental necrotizing lesions (P = 0.047). In LN, inverse associations were found between the presence of AECA and the duration of disease (P = 0.021), elevated serum creatinine levels (P = 0.020), decreased creatinine clearance (P = 0.043), and frequency of chronic renal failure (P = 0.036). Positive associations were observed between the presence of AECA and active lupus (P = 0.017), anti-nuclear antibodies (P = 0.015), and anti-DNA antibodies (P = 0.041). Our results suggest that AECA may be linked with the pathogenesis of LN and IgA N.
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PMID:Clinicopathologic associations of anti-endothelial cell antibodies in immunoglobulin A nephropathy and lupus nephritis. 837 32

Sixty HIV-infected patients presenting renal symptoms who underwent percutaneous renal biopsies were analysed. According to the CDC classification, 44 patients were staged in group IV, five in group III, and 11 in group II. Patients were divided in two groups according to their ethnic origin (29 black patients and 31 white patients). Risk factors such as homosexuality, multiple transfusions or intravenous drug abuse (IVDA) were identified in all white patients except two, but in only nine (31%) of the black patients. Three main patterns of renal disease were observed: focal and segmental glomerulosclerosis (FSGS) was found predominantly in black patients (23 black patients versus 3 Caucasians, P < 0.001) and was associated with the nephrotic syndrome; immune-complex-type glomerulonephritis (ICGN) was frequent in black and white patients (21% and 52% respectively) including four cases of IgA nephritis all seen in white patients; and 10 cases of lupus-like nephritis (4 black and 6 white patients). The frequent hypergammaglobulinaemia in those patients suggests a pathogenic role of polyclonal B cell activation in ICGN. Interstitial nephritis was present in 48 and 52% of the black and white patients respectively and did not seem related to drug toxicity or superimposed infectious disease. In addition to interstitial nephritis, the coexistence of multivisceral lymphocytic infiltration involving accessory salivary glands, liver and/or lung, found in six patients possibly suggests a virus-induced immune disorder.
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PMID:Renal disease associated with HIV infection: a multicentric study of 60 patients from Paris hospitals. 838 28

Glucocorticoids, cytostatic agents and cyclosporin are frequently employed in the treatment of glomerular diseases of immunologic origin. In order to assess the efficacy of these drugs, we retrieved--with the help of a Medline-based search--and analysed all controlled studies published since 1966 dealing with immunosuppressive therapy of glomerulonephritis. Of the 34 identified controlled studies, only 27 had a prospective and randomized design. In patients with minimal-change glomerulonephritis, proteinuria decreases and disappears during therapy with prednisone. A comparable effect can be obtained with cyclosporin. Occasionally, there is a relapse of proteinuria after cessation of the immunosuppressive therapy in some patients. These relapses can be controlled with a chlorambucil-based regimen. Chlorambucil may be successfully utilized in the treatment of focal-segmental glomerulosclerosis, a form of glomerulonephritis which is more refractory to glucocorticoid therapy and is probably pathogenetically related to minimal-change glomerulonephritis. Patients with membranous glomerulonephritis and a nephrotic syndrome seem to benefit from an alternate month prednisone and chlorambucil regimen. However, an indiscriminate treatment of all patients with this regimen is not legitimate, because some patients would be overtreated as the disease may undergo spontaneous remission. There are no well-documented valuable therapies for the IgA-associated glomerulonephritis and the membranoproliferative glomerulonephritis. The combination of prednisone with cytotoxic substances, particularly cyclophosphamide and azathioprine, seem to remarkably improve the renal prognosis of the diffuse proliferative lupus glomerulonephritis. The efficacy of cyclophosphamide and prednisone with or without plasma exchange in the treatment of the rapidly progressive glomerulonephritis due to other systemic diseases (M. Wegener, panarteritis nodosa, Goodpasture syndrome) is a widely accepted therapeutic modality, although controlled studies are lacking. Immunosuppressive therapy of glomerulonephritis bears notable risks and sometimes questionable efficacy. Thus, before prescribing any immunosuppressive therapy, it is mandatory to evaluate in every single patient the prognostic factors of the underlying disease, the probability of the onset of severe side effects and the possible acceptance of a renal replacement therapy, including renal transplantation.
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PMID:[Immunosuppressive therapy of glomerulonephritis--controlled studies]. 845 16

Three major components of the plasminogen activators (PA)/plasmin system are synthesized physiologically in glomeruli, and can be involved in glomerular proteolysis and extracellular matrix metabolism: tissue-type PA (tPA), urokinase (uPA) and PA inhibitor type 1 (PAI-1). To explore the possible role of a dysregulation of the plasmin protease system in the development and progression of lupus-like glomerulonephritis, we studied the expression of the renal plasmin protease components during the course of the disease, either acute, induced by IgG3 monoclonal cryoglobulins, or chronic, occurring spontaneously in three different lupus-prone mice: (NZBxNZW)F1, BXSB and MRL-lpr/lpr. RNase protection assays and in situ hybridizations revealed a marked glomerular induction of PAI-1 mRNA abundance without any significant changes in renal tPA and uPA mRNA levels in the two different types of lupus-like glomerulonephritis. The overexpression of PAI-1 mRNA occurred in parallel with a significant decrease in glomerular tPA-catalyzed enzymatic activity as determined by zymographic analysis. In addition, a concomitant increase in glomerular expression of transforming growth factor beta 1 (TGF-beta 1) mRNA was observed. The demonstration of a close correlation between the PAI-1 and TGF-beta 1 mRNA levels and the severity of lupus-like glomerular lesions suggests that a pertubation of the glomerular PA/PAI balance, resulting from a marked TGF-beta 1-mediated induction of PAI-1 gene expression, plays an important role in the progression of lupus-like glomerular lesions, leading to glomerulosclerosis.
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PMID:Induction of plasminogen activator inhibitor type 1 in murine lupus-like glomerulonephritis. 854 2

Susceptibility to systemic lupus erythematosus (SLE) and, in particular, lupus nephritis is strongly influenced by genetic factors. Previous studies have shown that MHC-related antigens influence the development of SLE. In the current study, we set out to investigate how non-MHC genes influence the pathogenesis of glomerulonephritis in chronic graft-versus-host disease (GVHD) in mice, a model for lupus nephritis. For the induction of GVHD we used parent-to-F1 hybrid mouse strain combinations. DBA/2, BALB/c, BALB.D2 and C57B1/10.D2 (BL10.D2) donor lymphocytes carrying an H-2d haplotype were injected into H-2b/d F1 hybrids of BL10 mice, which differed only at non-MHC loci. Within these hybrid strains the development of immune complex glomerulonephritis was investigated by monitoring the occurrence of autoantibodies in the circulation, deposition of immunoglobulins in the glomeruli, development of albuminuria, and glomerulosclerosis. In diseased DBA/2 mice albuminuria developed 6 weeks after induction of the disease. Mice with a BALB background developed a lupus-like syndrome characterized by albuminuria starting 8 weeks after induction of the GVHD. During the development of the GVHD, polyclonal B cell activation occurred in both the DBA/2 and BALB/c strains, resulting in the formation of autoantibodies. Only the strain combination using DBA/2 mice developed anti-GBM antibodies. In DBA/2 and BALB strain combinations immune complexes were detected in a granular pattern along the glomerular capillary walls. In the DBA/2 recipients a linear pattern of immunoglobulin depositions preceded the granular phase. This study demonstrates that: (i) non-MHC genes govern the pathogenesis of immune complex nephritis in this model by influencing the autoantibody profile; and (ii) the presence of anti-GBM antibodies in the early stages of the disease is a conditio sine qua non for the development of full-blown glomerulonephritis and glomerulosclerosis in this model.
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PMID:Non-MHC genes determine the development of lupus nephritis in H-2 identical mouse strains. 891 72

Eight patients with resistant and/or relapsing nephrotic syndrome or renal insufficiency were empirically treated with mycophenolate mofetil (MMF). The underlying glomerular diseases were membranous nephropathy (N = 3), minimal change disease (n = 2), focal segmental glomerulosclerosis (n = 1), and lupus nephritis (N = 2). Treatment with MMF 0.75 to 1.0 g twice daily, either as monotherapy or in combination with low-dose steroid treatment, resulted in substantial reductions in proteinuria or stabilization of serum creatinine. In relapsing patients following withdrawal from cyclosporin A, MMF achieved suppression of proteinuria equivalent to or better than that which occurred during cyclosporin A treatment. Steroids were successfully withdrawn in each of the non-lupus patients. MMF was well tolerated with no evidence of hematologic, hepatic, or other toxicity. These clinical anecdotes demonstrate the short-term clinical efficacy of MMF treatment. In addition, they suggest that MMF may have major steroid-sparing effects and might represent an alternative to cyclosporin A in appropriate patients.
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PMID:Successful mycophenolate mofetil treatment of glomerular disease. 946 13

Mice with chronic graft-versus-host disease (GvHD) induced by injection of DBA/2 lymphocytes into (DBA/2 x C57BL/10) F1 hybrids (DBA/2 GvHD) develop a lupus-like glomerulonephritis with global glomerulosclerosis 12 weeks after induction of the disease. In two other strain combinations with similar H-2 incompatibilities [BALB/c into BALB/c x BL10 (BALB/c GvHD) and BALB.D2 into BALB.D2 x BL10 (BALB.D2 GvHD)], GvHD induction leads to lupus nephritis without global glomerulosclerosis. This study investigated the identity of kidney-infiltrating leukocytes and their involvement in the development of glomerulosclerosis in these three strain combinations. In mice with DBA/2 GvHD, a significant increase in glomerular CD11a-positive cells was found 4 weeks after disease induction. Mice with BALB/c or BALB.D2 GvHD did not show an increase in glomerular CD11a-positive cells at any time point. In the interstitium, CD11a-positive cells were observed 4 weeks after disease induction only in mice with DBA/2 GvHD. In mice with BALB.D2 GvHD, no increase was found in interstitial CD11a-positive cells. In mice with BALB/c GvHD, interstitial CD11a-positive cells were found from week 4 onward. Further immunohistochemical analysis of the glomerular CD11a-positive cells in mice with DBA/2 GvHD showed that these cells were neither polymorphonuclear leukocytes (PMN), nor CD3-positive (T cells), B220-positive (B cells), or F4/80-positive (macrophages). They were all CD45-positive (leukocytes) and MHC class II-positive. In conclusion, we have shown in this model of chronic lupus nephritis that glomerular influx of as yet unidentified CD11a-positive leukocytes is associated with the development of glomerulosclerosis.
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PMID:Association between leukocyte infiltration and development of glomerulosclerosis in experimental lupus nephritis. 960 15

We describe here the broad spectrum of acute renal insufficiency occurring in the course of human immunoinsufficiency virus infection. In our renal unit in Tenon hospital, 90 human immunoinsufficiency virus-infected adult patients were admitted for acute renal insufficiency between June 1988 and December 1996. Sixty out of them had a pathological diagnosis. The remaining patients did not have renal biopsy because of obstructive renal failure (n = 2), bleeding risk (n = 11), or clinically evident hypovolemic and/or sepsis-related acute tubular necrosis (n = 17). Nine different causes of acute renal insufficiency were listed. Human immunoinsufficiency virus-associated nephropathy, the most specific human immunoinsufficiency virus-related renal disease, which was diagnosed in 14 patients, is characterized by focal and segmental glomerulosclerosis with an important hyperplasia and/or proliferation of podocytes and huge tubular distension. The rapid progression to end-stage renal failure was not a constant feature since 10/14 patients had a partial renal recovery. Hemolytic-uremic syndrome was the other major cause of acute renal failure in these patients (32 cases) and was found to be associated with active cytomegalovirus infection. Cytomegalovirus-infected cells were present in half of the renal biopsies performed in this group of patients. Furthermore, these patients had an increased plasma tissue-type plasminogen activator activity whereas its type 1 inhibitor was not significantly increased, as opposed to non human immunoinsufficiency virus-associated hemolytic-uremic syndrome. Half of the patients had a complete renal recovery. The other causes of acute renal insufficiency were 1) intratubular deposition of either drugs (Adiazine, Foscavir, Indinavir) in 13 patients, or monoclonal light chain in one patient with B cell-lymphoma; 2) lupus-like glomerulonephritis characterized in one case by a complete clinical remission after 6 month-treatment by antiproteases; 3) acute tubular necrosis. In this setting, rhabdomyolysis could reveal HIV infection. The heterogeneity of renal diseases could be explained by the variation of human immunoinsufficiency virus-associated infections along time and by the different drugs which permit a better survival. We can hypothesize that new HIV-associated diseases will occur with the long term use of antiproteases.
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PMID:[Human immunodeficiency virus and acute renal insufficiency]. 961 98

There is little data on the spectrum of renal diseases in the United Arab Emirates. A renal diseases registry has been set up in an attempt to address this issue nationwide, and we report here the first outcome of this endeavor, a retrospective histopathologic analysis of 490 native kidney biopsies performed on adult patients presenting to four hospitals in the Emirate of Abu Dhabi from 1978 to June 1996. The most common indication for a biopsy was the nephrotic syndrome (54.0%), followed by asymptomatic urinary abnormalities (29.7%), and chronic renal failure (12.7%). Primary glomerular disease accounted for 77.1% of all biopsies. Chronic proliferative glomerulonephritis as a group was the predominant pathology (36.2%), followed by idiopathic membranous glomerulopathy (20.1%), focal segmental glomerulosclerosis (18.3%), minimal change nephropathy (18.3%), and IgA nephropathy (6.3%). Of the patients with secondary kidney diseases, 33 (40.7%) had systemic lupus erythematosis, 27 (33.3%) amyloidosis, 14 interstitial nephropathy, and seven diabetic nephropathy. Kidney biopsies of 187 patients with primary glomerular disease who presented with the nephrotic syndrome were analyzed. In this group idiopathic membranous glomerulopathy, proliferative glomerulonephritis, and minimal change glomerulopathy was found in almost equal proportions (28.3%, 26.6%, 26.2%) with focal segmental glomerulosclerosis (15.4%) accounting for the bulk of the remainder. Though the overall results of this analysis do not show any major differences in the spectrum of primary glomerulopathies in the United Arab Emirates compared with other countries, a slight tendency towards a higher frequency of focal segmental glomerulosclerosis among patients indigenous to the Arabian Peninsular (20.4%) deserves further evaluation.
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PMID:Analysis of 490 kidney biopsies: data from the United Arab Emirates Renal Diseases Registry. 965 Jan 23


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