Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the past decade, experimental and clinical evidence has indicated an important role for the renin-angiotensin system in the progressive destruction of nephrons in a wide variety of chronic renal diseases. Studies have indicated that in the subtotally nephrectomized rat model of progressive glomerulosclerosis, in experimental diabetes mellitus, in the chronic phase of puromycin aminonucleoside-induced nephrotic syndrome and in Heymann's nephritis, angiotensin-converting enzyme (ACE) inhibitors dramatically preserve both nephron structure and function. Clinical studies have similarly noted that chronic administration of ACE inhibitors inhibits progression of renal failure in type I diabetes and type II diabetes as well as primary glomerulopathies, sickle cell nephropathy, systemic lupus erythematosis, chronic pyelonephritis and adult polycystic kidney disease. Current evidence suggests that the beneficial effect of ACE inhibitors is primarily due to inhibition of angiotensin II production, and there is strong suggestive evidence for increases in local intrarenal activation of the renin-angiotensin system in these conditions. In obstructive uropathy, activation of the renin-angiotensin system has also been shown to be an important aspect of the early functional changes and may be of importance in the subsequent generation of interstitial fibrosis. In the obstructed kidney, renin and angiotensinogen production increase and type I angiotensin receptors decrease. Inhibitors of angiotensin II production and angiotensin II action partially reverse the vasoconstriction and the reduced renal blood flow, and abolish the changes in expression of AT1 MRNA induced by obstruction. Studies suggest that the angiotensin-mediated increases in tubulointerstitial fibrosis may be mediated by increased production of transforming growth factor-beta.
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PMID:Angiotensin II-mediated renal injury. 756 81

Recent studies in our laboratories have shown that urine from healthy adults contains immunoreactive and intact insulin-like growth factor-binding protein-3 (IGFBP-3). The aim of this study was to assess urinary IGF-I, IGF-II, and IGFBP-3 in a cross-sectional study of healthy subjects, as well as characterize urinary IGFBPs (uIGFBps) in patients with GH deficiency (GHD) and renal disease, such as, Alport syndrome, immunoglobulin A nephropathy, focal segmental glomerulosclerosis, and systemic lupus erythematosus. Urinary concentrations of IGF-I and IGF-II in pooled spot morning urines of healthy subjects, measured by RIA, were low and relatively unaltered throughout age, when expressed as either nanograms per milliliter or nanograms per milligram creatinine. To determine the complement of IGFBPs in urine of healthy subjects, spot morning urine samples were subjected to Western ligand blot and immunoblot analysis. IGFBP-3 was detected at 40-50 kDa, possibly due to variable glycosylation of uIGFBP-3. In addition, a 32-kDa IGFBP-2 and smaller unclassified IGFBPs were detected. Unlike uIGFs, urinary concentrations of IGFBP-3 (uIGFBP-3; nanograms per milligram creatinine) were age-, but not sex-related. Levels of uIGFBP-3 ranged from 40-60 ng/mL in children between 4 and 10 yr of age. After 11 yr, immunoreactive uIGFBP-3 progressively declined, attaining a plateau after 26 yr of age to approximately 18 ng/mg creatinine. uIGFBP-3 did not correlate with uIGF levels. Regulation of IGFBP-3 in the urine of normal subjects and of renal disorders was examined by RIA, Western ligand blot (WLB), and protease assay. Intact uIGFBP-3 was consistently found in normal urine and little urinary protease was identified. In GHD patients, IGFBP-3 by WLB was low or undetectable, whereas RIA levels of uIGFBP-3 were normal or high, consistent with the presence of IGFBP-3 proteolytic activity. In Alport syndrome, both RIA measures and WLB analysis were high, as was the IGFBP-3 proteolytic activity. Patients with immunoglobulin A nephropathy, focal segmental glomerulosclerosis and systemic lupus erythematosus measured low-normal levels of IGFBP-3 by WLB and RIA, and displayed little protease activity. This study provides normative data concerning radioimmunoassayable levels of IGFBP-3 in urine. The presence of normal-elevated levels of uIGFBP-3 by RIA in GHD indicates that uIGFBP-3 levels are not under GH control and are unlikely to represent filtered serum IGFBP-3.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Urinary insulin-like growth factors (IGF) and IGF-binding proteins in normal subjects, growth hormone deficiency, and renal disease. 768 45

Laminin (LAM) and fibronectin (FI) are regarded as major components of the glomerular extracellular matrix. The aim of this study was to define the distribution of LAM and FI in primary glomerulonephritis (GN) and GN of systemic lupus erythematosus (SLE) and to correlate the type of glomerular disorders with possible changes in the expression of these components. Normal portions of kidney tissue from 10 patients with renal tumors and sixty-six renal biopsies obtained from patients with GN were studied by the immunoperoxidase-antiperoxidase (PAP) method for the detection of LAM and FI. Twelve patients had membranous GN (MGN), 8 mesangiocapillary GN (MCGN), 21 mesangioproliferative GN (MPGN), including 11 cases of IgA nephropathy, 11 focal segmental glomerulosclerosis (FSGS) and 14 had SLE. In MGN, LAM was detected more intensely than FI along the glomerular basement membranes (GBM), in subepithelial GBM protrusions and in the newly-formed GBM. On the contrary, FI was intensely expressed in the mesangium. LAM and FI expression was pronounced in stages II and III of MGN. In MCGN, LAM and FI were diffusely expressed along the GBM and in the mesangium. The distribution of the two antigens in MPGN and FSGS was similar to that seen in normal glomeruli. However, the FI staining reaction was more intense in severe mesangioproliferative lesions, mainly observed in the cases of IgA-nephropathy. There were no differences in the distribution of LAM and FI between primary and SLE GN. The antigen staining pattern was pronounced in the membranous and mesangiocapillary lesions of SLE GN.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The glomerular distribution of laminin and fibronectin in glomerulonephritis. 768 70

Proteinuria was characterized by SDS-PAGE and by immunoblotting with anti-human albumin sera for the detection of urinary polymers of albumin (PA) in 40 patients with biopsy proven lupus glomerulonephritis (LN) (6 pts class III WHO, 24 pts class IV, 10 pts class V) with various clinical presentations (nephrotic syndrome with normal or impaired renal function, 14 pts; urinary abnormalities with normal or impaired renal function, 21 pts; clinical remission, 5 pts); in 25 pts, for whom the characterization of proteinuria and the renal biopsy were performed at the same time, the activity and chronicity index scores were calculated. The mixed SDS-PAGE patterns, characterized by the presence of low molecular weight proteins, were the more frequently found; the mixed patterns were significantly associated with interstitial leukocyte infiltration (p = 0.05) and glomerular sclerosis (p = 0.046) and nonsignificantly associated with higher values of serum creatinine; no SDS-PAGE pattern had predictive value on functional outcome at 36 months. Albumin polymers were present in 67% of pts; in active disease they were present in 33% of class III, in 100% of class IV and in 45% of class V WHO (p = 0.026); PA were not present in 5 pts with clinical remission (4 class IV and 1 class V WHO). The presence of PA was significantly associated with high values (> 10) of activity index (p = 0.009) and with extracapillary proliferation (p = 0.041). Serum creatinine was lower in patients without PA (Scr 1.0 +/- 0.4 mg/dl) than in those with PA (Scr 1.5 +/- 1.0 mg/dl), but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:SDS-PAGE patterns and polymeric albumin in proteinuria of lupus glomerulonephritis. 773 85

Epidermal growth factor (EGF), a polypeptide with a potent mitogen activity, and its receptor [EGFR] have been previously identified in the kidney, but their expression in normal and diseased kidneys has not been fully elucidated. In order to evaluate EGFR in various histological types of renal injury, EGFR expression was studied by the immunohistochemical avidin-biotin complex (ABC) method with a monoclonal antibody EGFR1 on paraffin sections from 10 normal kidneys, 56 renal biopsies with various types of glomerulonephritis (GN), and 20 renal grafts with rejection. EGFR expression was observed in (a) 3 of 10 (30%) normal kidneys, (b) 17 of 39 (43.6%) renal biopsies with various types of GN mainly in membranous GN (57%) and in focal segmental glomerulosclerosis (FSG) (62.5%), (c) 6 of 17 (35.3%) biopsies with various types of systemic lupus erythematosus GN, and (d) 12 of 20 (60%) renal grafts with acute (42.9%) and chronic (69.2%) rejection. EGFR was mainly localized to the epithelial cells of the distal and collecting tubules and extraglomelar vessels, while it was observed less frequently in parietal epithelial cells and along glomerular basement membranes. Notably EGFR was detected in the epithelial cells adjacent to adhesions with Bowman's capsule and in the connective tissue of fibrocellular crescents. In conclusion, EGFR expression was observed more frequently in diseased than in normal kidneys. The increased incidence of EGFR expression in FSG, in chronic rejection, in small adhesions with Bowman's capsule and fibrocellular crescents suggest that EGF/EGFR may be correlated with a disturbed extracellular matrix production resulting in formation of early sclerotic lesions.
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PMID:Immunohistochemical study of epidermal growth factor receptor (EGFR) in various types of renal injury. 797 Jan 18

The urinary transforming growth factor beta (TGF-beta) excretion was measured in 33 patients including 10 with systemic lupus erythematosus (SLE), 8 with focal glomerular sclerosis (FGS), 9 with IgA nephropathy (IgAN), and 6 with membranous nephropathy (MN), and in 7 healthy subjects by enzyme-linked immunosorbent assay using a monoclonal antibody specific for TGF-beta 1 + 2 + 3. A significantly increased urinary TGF-beta excretion was observed in FGS patients (555.5 +/- 458.4 ng/mg Cr) as compared with normal controls (46.9 +/- 43.9 ng/mg Cr) (p < 0.05) and a relative increase in SLE patients (96.4 +/- 58.2 ng/mg Cr) and a decrease in MN patients (24.8 +/- 13.3 ng/mg Cr). In contrast, there was no difference in TGF-beta excretion between IgAN patients (54.1 +/- 37.4 ng/mg Cr) and normal controls. A correlation between the amount of proteinuria and TGF-beta was not found. As has been previously demonstrated in experimental studies, TGF-beta may play a similar role in human glomerular diseases. The results obtained in this study raised the possibility that extracellular matrix might be produced by glomerular cells in vivo under the control of TGF-beta and that TGF-beta might act as a stimulator for the development of glomerulosclerosis.
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PMID:Increased excretion of urinary transforming growth factor beta in patients with focal glomerular sclerosis. 801 40

We investigated the frequency and distribution of glomerular thrombosis (GT) in 108 renal biopsies of lupus patients and correlated this finding with the presence of anticardiolipin antibodies (ACLA). GT was present mainly in the diffuse proliferative form. The activity index was higher in those patients with GT (12.9 +/- 4.7 vs 5.4 +/- 4.1, P < 0.01). The more severe histologic features, necrosis and extracapillary proliferation were also related with GT. In 18 cases with repeated biopsy the best predictors for the subsequent development of glomerular sclerosis were fibrinoid necrosis (P < 0.01), glomerular infiltration (P < 0.01) and an activity index of 10 or more (P < 0.05). GT also showed to be an important prognostic factor for sclerosis, although no statistically significant. ACLA were investigated in 36 patients at the time of renal biopsy. There were nine positive cases and in three of them this finding was related to GT. We can conclude that GT is a relevant feature showing active lupus nephritis and that it is not related to the presence of ACLA.
Lupus 1994 Feb
PMID:Renal biopsy in systemic lupus erythematosus: significance of glomerular thrombosis. Analysis of 108 cases. 802 81

Renal involvement is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Histologic examination of renal tissue using light microscopy, immunofluorescent staining, and electron microscopy permit identification of glomerular immune complex deposits in virtually all patients with SLE. We report a patient who fulfilled four American College of Rheumatology criteria for the classification of SLE whose clinical course was consistent with SLE, yet whose renal failure resulted from focal glomerulosclerosis that was not mediated by immune complexes. The characteristics of this case of focal glomerulosclerosis that differentiate it from healed focal proliferative glomerulonephritis are discussed.
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PMID:Idiopathic focal segmental glomerulosclerosis in a patient with systemic lupus erythematosus: an unusual combination. 797 36

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

In many renal diseases, glomerular thrombosis may play an important role in the development of glomerular sclerosis and progression of renal failure. The aim of this study was to assess the effect of antiplatelet agents on the evolution of patients with chronic glomerular disease. Twenty four patients aged 48 +/- 17 years (21 with idiopathic glomerulonephritis, one with systemic lupus erythematosus and two with type II diabetes mellitus) were treated with aspirin and dipyridamole or aspirin alone during 23.9 +/- 17.5 months. The patients were followed during 31.8 +/- 23 months; seven patients had a progressive deterioration of renal failure requiring dialysis or transplantation (Group A) and 17 had a stable or improving renal function (Group B). Initial serum creatinine was significantly higher in group A than in group B (3.6 +/- 1.6 vs 1.5 +/- 1.5 mg/dl respectively p = 0.003); no other significant differences in the initial assessment were observed between both groups. It is concluded that antiplatelet agents may delay the progression of renal disease when started in patients with normal or slightly deteriorated renal function.
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PMID:[Is it justifiable to use antiplatelet drugs as a universal protection in patients with chronic glomerular damage?]. 824 41


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