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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease marked by immune-complex mediated lesions in small blood vessels of various organs, especially the kidneys, although other factors may also be implicated in the pathogenesis of the disease. This article focuses on the role of lipids in the progression of glomerular, vascular and tubulo-interstitial lesions in two patients with lupus nephritis associated with pronounced hyper- and dyslipidemia. The pathogenesis of progressive glomerulosclerosis in both patients appears to be multifactorial. In addition to immune complex mediated lupus glomerulonephritis, progressively active in the first patient, severe nephrotic-range persistent proteinuria, arterial hypertension associated with hyperfiltration and hyperperfusion injuries and, to a minor extent, hyper- and dyslipidemia were observed. Immunological and non-immunological factors were shown to contribute to the development of tubulo-interstitial lesions. In both patients, in addition to local immune deposits, prominent tubulo-interstitial lipid deposits were probably causally related to both hyperlipidemia and the increased permeability of the glomerular filtration barrier. Tubular lesions were highlighted by intracytoplasmic lipid droplets as well as small cleft-like spaces found to be impacted in the tubular lumina. They were seen to penetrate tubular epithelial cells and eventually lodge in the interstitium, surrounded by mononuclear cell infiltrates and foam cells. In both patients, hypertensive angiopathy and extraglomerular vascular immune deposits were demonstrated. In addition, in the second patient, arteriolar and small arterial hyaline was found at the age of 28 years to be full of lipids and calcium precipitates, suggesting a peripheral atherosclerosis-like process which never occurs as a natural age-related condition. In conclusion, all parts of the nephron may be involved in the pathogenetic process causally related or influenced by hyper- or dyslipidemia. Associated either with endothelial cell injury and consequent insudation of lipids in the vascular walls, glomerular filtration barrier injury with hyperfiltration, or tubulo-interstitial lipid deposition, the mechanism of tissue damage by lipids in all parts of the nephron shares similarities with the pathogenesis of systemic atherosclerosis.
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PMID:Role of lipids in the progression of renal disease in systemic lupus erythematosus patients. 1102 Sep 63

To date, the underlying diseases and follow-up of Taiwanese children screened by urinalysis have not been reported. The grading of urine abnormalities varied from grade A (microscopic hematuria only), grade B (light proteinuria only), grade C (light proteinuria and microscopic hematuria) to grade D (heavy proteinuria). From January 1991 to August 1998, 630 students, aged 6-15 years and with positive urinary screening, were admitted to our hospital for further evaluation. Of these, 573 students had confirmed abnormal findings, 298 were boys, 275 were girls, and 294 students received a renal biopsy and have had regular follow-up visits. This study was designed to retrospectively elucidate: (1) the relationship between grading of urine abnormality and underlying disease; (2) the relationships among hypertension, grading of urine abnormality, and underlying disease; (3) the underlying disease of low serum C3 level; and (4) to determine whether urinary screening progressively decreased the number of students with end-stage renal disease (ESRD) annually. The results show that glomerular nephritis (GN) is still one of the major causes of urinary abnormalities. The most-important secondary GN was systemic lupus erythematosus (SLE) with lupus nephritis. One-quarter of the patients fulfilled at least four of the revised American Rheumatology Association (ARA) criteria for SLE at first administration, while the others who fulfilled only two to three of the revised ARA criteria had gradually developing signs and symptoms of SLE at follow-up. The percentage of SLE patients amongst anti-nuclear antibody (ANA) positive children was 72%. Membranoproliferative GN is very rare. The distribution of hypertension was 8.2% in grade A, 10.7% in grade B, 9.7% in grade C, and 28.9% in grade D urinary abnormality. There were statistical differences between grade D and either grade A or B or C (P<0.05). Lower serum C3 levels were found only in a minority of patients, including those with SLE. In this series, focal segmental glomerular sclerosis (FSGS) and active class IV lupus nephritis patients were found early enough to receive methylprednisolone pulse plus cyclosporine A therapy. To date there have been only 2 cases (5%) of FSGS with impaired renal function, and none of the lupus nephritis patients are in the predialysis stage. In conclusion, GN is still the major cause of urinary screening abnormality. ANA study is indicated in all Chinese students with abnormal urinary screening. The correlations between the severity of proteinuria and hypertension showed more-severe proteinuria in patients with nephritis as well as in those with hypertension.
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PMID:The underlying diseases and follow-up in Taiwanese children screened by urinalysis. 1132 70

Overexpression of inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of lupus glomerulonephritis. Mycophenolate mofetil (MMF), a novel immunosuppressive agent, is currently used in organ transplantation and under evaluation for treatment of autoimmune disorders. Mycophenolic acid, the active metabolite of MMF, has been shown to suppress cytokine-induced nitric oxide production in vitro. The aim of this study was to evaluate the effect of MMF on the expression of renal cortical iNOS mRNA and protection against glomerulonephritis in MRL/lpr mice. Three-month-old MRL/lpr mice (n = 6) displaying clinical symptoms of glomerulonephritis were treated for 3 months with MMF (90 mg/kg/day) dissolved in a vehicle. Controls were age- and sex-matched mice (n = 6) that received the vehicle alone. By reverse-transcription competitive polymerase chain reaction, we found that the renal cortical iNOS/beta-actin mRNA ratio was reduced by 30.8% (P <.05) in MMF-treated mice. Furthermore, MMF significantly reduced urinary nitrite production and degree of glomerulosclerosis. The glomerular volume was reduced by 17.5% (P <.001). Proteinuria was also significantly reduced in the MMF-treated group. However, by electrophoretic mobility shift assay, the nuclear binding of nuclear factor-kappaB (NF-kappaB) was not affected by MMF treatment. We conclude that in addition to its immunosuppressive action, MMF may reduce renal cortical iNOS mRNA expression and diminish glomerulosclerosis in MRL/lpr mice independent of modulation of the NF-kappaB pathway.
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PMID:Mycophenolate mofetil reduces renal cortical inducible nitric oxide synthase mRNA expression and diminishes glomerulosclerosis in MRL/lpr mice. 1143 30

For various ethnic and socioeconomic reasons the pattern of renal disease in the inner city displays distinctive features. Hypertension is frequent, often intractable, and generally conditioned by salt sensitivity and a high sodium intake. Chronic hypertensive nephrosclerosis, found predominantly in African Americans, comprises marked cardiomegaly, renal shrinkage, and hypertensive retinopathy. It has been overdiagnosed in the past, but actually accounts for less than 20% of end-stage renal disease (ESRD) in African Americans. Malignant hypertension, less frequent nowadays, may cause renal shutdown, which is reversible in a few cases; the heart and kidneys are often of normal size. Idiopathic focal segmental glomerulosclerosis is the most common cause of the primary nephrotic syndrome in blacks, but its incidence has also been rising in whites and Hispanics; it does not respond well to treatment, and almost one half of the patients develop ESRD within 10 years. Systemic lupus erythematosus is also more common in African Americans, in whom the severe proliferative forms of lupus nephritis pursue a more virulent course: one half of such patients develop ESRD in 5 years. Cocaine, the use of which has assumed epidemic proportions, may cause accelerated hypertension, acute renal failure from rhabdomyolysis, and progression of preexisting renal disease. Heroin nephropathy has all but disappeared and has been replaced by human immunodeficiency virus (HIV) nephropathy. The prognosis of HIV-infected patients maintained by dialysis has greatly improved. Sickle glomerulopathy, consisting of mesangial expansion, basement membrane duplication, and the absence of immune deposits, may cause the nephrotic syndrome in 4% of patients with severe sickle cell anemia, heralding death within 2 years in one half of patients and ESRD in two thirds; survival has not improved with dialysis. Diabetes is now the most common cause of ESRD. Familial aggregation of ESRD is frequently encountered. Interventions useful in the general population, such as vascular bypass procedures, should be undertaken with great caution and restraint in dialysis patients.
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PMID:Renal disease in the inner city. 1145 21

We experienced a case of lupus nephritis with antiphospholipid antibody syndrome. A renal biopsy specimen from this patient showed various renal histological changes, but the results of urinalysis were almost normal. The patient was a 56-year-old woman diagnosed as having systemic lupus erythematosus with antiphospholipid antibody syndrome in 1983. In 1998, she had diarrhea and blood gas analysis showed metabolic acidosis. Therefore, she was admitted to our hospital and underwent renal function examination. The glomerular filtration rate was reduced(GFR: 40/ml/min), but urinalysis was almost normal. To examine her renal dysfunction, we performed open renal biopsy. Her renal tissues showed global glomerular sclerosis, mesangial cell proliferation and infiltration of cells in the tubulointerstitial area(WHO II). Furthermore, some arterioles showed organized thrombus formation and recanalization due to the antiphospholipid antibody syndrome. Renal biopsy of patients with lupus nephritis is useful not only for precise diagnosis, but also for the selection of appropriate treatment.
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PMID:[A case of antiphospholipid antibody syndrome with variable renal histological change despite of poor changes in urinalysis]. 1151 Feb 27

Among NZB/W-derived New Zealand mixed (NZM) strains, only NZM/Aeg2410 (NZM2410) has been well characterized. In contrast to NZM2410, NZM2328 mice develop autoantibodies and acute and severe chronic glomerulonephritis (GN) with female predominance similarly to NZB/WF1 and humans with systemic lupus erythematosus (SLE). Chronic GN with glomerular sclerosis and tubular atrophy but not acute GN was correlated with severe proteinuria. In a backcross analysis of (NZM2328 X C57L/J) F1 X NZM2328, four SLE susceptibility genomic intervals were identified. One of them (Cgnz1) is on the telomeric end of chromosome 1 and close to Sle1. It was significantly linked to chronic GN. A locus (Agnz1) distinct from Cgnz1 on this interval was suggestively linked to acute GN. Two genetic intervals on chromosome 17 were also suggestively linked to acute GN, one of which is the H-2-Tnf complex, while the other (Agnz2) is on the distal end of the chromosome. A single locus (Adaz1) identified in the midregion of chromosome 4 in NZM2328 mice was suggestively linked to plasma levels of IgG anti-dsDNA autoantibodies. These results differ significantly from those in the backcross analysis of (NZM2410 X C57BL/6)F1 X NZM2410 by other investigators. They support the concept that different sets of genes are involved in acute and chronic GN. The genomic differences between the NZM strains and between C57L/J and C57BL/6 account for the differences between our analysis and that on NZM 2410. These results provide evidence for the importance of background genes on the expression of SLE, with implications for genetic studies of human SLE.
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PMID:NZM2328: a new mouse model of systemic lupus erythematosus with unique genetic susceptibility loci. 1151 51

In systemic lupus erythematosus, plasma concentrations of tumor necrosis factor alpha (TNF alpha) and other pro-inflammatory cytokines are elevated and those of transforming growth factor beta (TGF beta) are decreased. TNF alpha prevents lupus nephropathy whereas increased concentration of TGF beta causes glomerulosclerosis. Insulin inhibits TNF alpha and enhances TGF beta production, augments nitric oxide synthesis and blocks superoxide anion generation. Polyunsaturated fatty acids (PUFAs) also have actions similar to insulin. Hence, it is suggested that a combination of insulin (in the form of glucose-insulin-potassium) and PUFAs may be of benefit in lupus and other inflammatory conditions.
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PMID:Hypothesis: can glucose-insulin-potassium regimen in combination with polyunsaturated fatty acids suppress lupus and other inflammatory conditions? 1154 28

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a pathogenic role in experimental crescentic glomerulonephritis (GN). Renal expression of MIF is also upregulated in human GN and correlates with leukocytic infiltration, histologic damage, and renal dysfunction. The study presented here examined whether MIF can be measured in urine and if so, whether the urine MIF concentration reflects the degree of renal injury. Urine and serum MIF was measured by enzyme-linked immunosorbent assay in 10 normal healthy volunteers and in a cohort of 63 patients with GN (2 thin basement membrane disease [TBM], 15 membranous GN, 10 focal segmental glomerular sclerosis, 20 IgA glomerularnephritis, 11 crescentic GN, 10 systemic lupus erythematosis World Health Organization class IV). Renal MIF expression was assessed by immunostaining of biopsy tissue. MIF was detected in urine from normal volunteers (mean +/- SD; 191 +/- 132 pg MIF/micromol creatinine). The urine MIF concentration was unchanged in patients with nonproliferative nephropathies (343 +/- 397 pg MIF/micromol Cr) but was increased 3.4-fold in proliferative nephropathies (645 +/- 527 pg MIF/micromol Cr; P < 0.05 versus normal and nonproliferative). Stratified analysis showed the greatest increase in urine MIF in crescentic GN (4.5-fold). In contrast, serum MIF levels were not different between normal patients and any patient group. Immunostaining demonstrated a significant increase in renal MIF expression in proliferative glomerulonephritides that was associated with macrophage and T cell infiltration. There was a significant correlation between the urine MIF concentration and renal MIF expression, but not with serum MIF, indicating a renal origin for the excreted urine MIF. The urine MIF concentration also correlated with the degree of renal dysfunction, histologic damage, and leukocytic infiltration, but not with the amount of proteinuria. In conclusion, this study shows that the urine MIF concentration is significantly increased in proliferative forms of GN and correlates with the degree of renal injury. Urine MIF levels reflect MIF expression within the kidney and may be a useful noninvasive tool for monitoring patients with crescentic GN, particularly in disease exacerbation.
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PMID:Urine macrophage migration inhibitory factor reflects the severity of renal injury in human glomerulonephritis. 1179 56

The molecular characterization of changes in mRNA expression in renal tissue during disease is hampered by the acquisition of sufficient mRNA to do genomewide expression profiling. In many renal diseases, such as systemic lupus erythematosus, IgA nephropathy, antineutrophil cytoplasmic autoantibody (ANCA) associated glomerulonephritis, and small-vessel vasculitis (ANCA disease), circulating leukocytes play a role in onset, progression, and severity of the condition. Circulating leukocytes are readily isolated and supply sufficient mRNA for analysis, allowing molecular investigation into their involvement in the disease process. Our laboratory has undertaken a systematic study of the genomewide expression profiles of the circulating leukocytes from patients with a variety of renal diseases (ANCA disease, IgA nephropathy, lupus nephritis, focal segmental glomerulosclerosis), using the Affymetrix high-density gene chip array technology. Analysis of the data showed clustering of expressed genes unique for each individual disease group. These results imply that significant gene expression changes occur in leukocytes that are circulating in patients with renal diseases. In addition, gene expression has been studied in leukocytes activated in vitro by mechanisms that mimic pathogenic events in vivo. The expression levels of genes identified in in vitro studies were compared with the patient leukocyte gene expression to determine whether similar pathological events were occurring in vivo.
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PMID:Microarray studies of gene expression in circulating leukocytes in kidney diseases. 1193 61

Uteroglobin (UG) is a multifunctional protein with anti-inflammatory/immunomodulatory properties. The UG gene is located on the long arm of chromosome 11 (11q12.3-q13.1) in a region linked to some immune disorders. A guanine-adenine substitution at position 38 (A38G) has been found in the noncoding region of exon 1 that is significantly correlated with an increased risk of developing immune-mediated diseases. Recently an experimental model of UG knockout mice showed that in mice, UG deficiency causes severe glomerulopathy with mesangial deposition of IgA-fibronectin complexes. To detect the presence of polymorphisms in the UG coding sequence, the DNA of 109 patients with IgA nephropathy (IgAN), and 32 patients with systemic lupus erythematosus (SLE) were tested for the nucleotide sequence of all three UG exons by heteroduplex analysis. We detected heterozygous DNA only for exon 1 due to the A38G substitution, as confirmed by sequencing. We tested for A38G polymorphism, by restriction endonuclease digestion (Sau96I), both in SLE patients and in IgAN patients. Twenty patients with either membranous nephropathy (12) or focal and segmental glomerular sclerosis and 120 healthy subjects served as controls. Compared with both healthy controls and non-IgA control patients, the frequency of the 38A allele was significantly higher in SLE patients (38 of 64 alleles versus 89 of 240 alleles, p = 0.002, and versus 7 of 40 alleles, p < 0.001). IgAN patients showed an allelic distribution similar to both control groups. A subgroup of 18 IgAN patients undergoing renal replacement therapy because of end-stage renal disease showed a significant increase in 38A allele frequency (5 of 36 38G alleles versus 31 of 36 38A alleles, p < 0.001). UG is an immunomodulatory agent that is able to (a) inhibit the activity of several phospholipase A2 (PLA2s), (b) interfere with the function of both neutrophils and monocytes, and (c) prevent immune recognition, perhaps by masking surface antigens. This could account for the role this molecule plays in SLE. The A38G polymorphism is located within a region corresponding to the rat minimal promoter that proved to be important in the transcriptional regulation of UG. Although the significance of any alterations in the UG exon 1 noncoding region in humans has yet to be clarified, initial evidence suggests that it may alter the control of immune response and of inflammation.
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PMID:Polymorphism of the uteroglobin gene in systemic lupus erythematosus and IgA nephropathy. 1200 94


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