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

The clinical manifestations of drug-induced renal disease may include all the manifestations attributed to natural or spontaneous renal diseases such as acute renal failure, chronic renal failure, acute nephritic syndrome, renal colic, haematuria, selective tubular defects, obstructive nephropathy, etc. It is therefore vital in any patient with renal disease whatever the clinical manifestations might be, to obtain a meticulous drug and toxin inventory. Withdrawal of the offending drug may result in amelioration or cure of the renal disorder although in the case of severe renal failure it may be necessary to utilise haemodialysis or peritoneal dialysis to tide the patient over the period of acute renal failure. Analgesic nephropathy is an important cause of terminal chronic renal failure and it is therefore vital to make the diagnosis as early as possible. The pathogenesis of some drug-induced renal disorders appears to be immunologically mediated. There are many other pathogenetic mechanisms involved in drug-induced renal disorders and some drugs may under appropriate circumstances be responsible for a variety of different nephrotoxic effects. For example, the sulphonamides have been incriminated in examples of crystalluria, acute interstitial nephritis, acute tubular necrosis, generalised hypersensitivity reactions, polyarteritis nodosa and drug-induced lupus erythematosus.
 ...
PMID:Drug-induced renal disease. 38 1

A 17-year old-male presented with a 6-week history of weight loss, lassitude and calf pains. On examination he was very pale. Laboratory tests showed a very high erythrocyte sedimentation rate (155 mm in the first hour), anaemia (haemoglobin 10.1 g/dl), and a raised serum creatinine of 1.54 mg/dl. Microhaematuria (5-10 erythrocytes/microliter) and pronounced pyuria (500 leucocytes/microliter) were present, but the urine was sterile and there was no increase in albumin excretion. The serum IgG was raised to 75.7 g/l, suggesting an autoimmune disorder. Anti-nuclear antibodies (titre 1 : 1920) and anti-double-stranded DNA antibodies (31 U/ml) were present, while the serum complement C4 was decreased to 0.11 g/l. Renal histology showed an interstitial nephritis without glomerular involvement, while the bone marrow showed vasculitis accompanied by a prominent plasma-cell infiltrate. A diagnosis of interstitial nephritis associated with systemic lupus erythematosus was made, with asymptomatic cardiac and hepatic involvement. Renal function recovered rapidly with prednisolone therapy (initial dose 2 mg/kg.d). While glomerulonephritis is the most common lupus-associated renal disorder, isolated interstitial nephritis may occur in some cases, often with an absence of proteinuria.
 ...
PMID:[Interstitial lupus nephritis]. 158 9

We have conducted an immunocytochemical analysis to investigate the presence of the recently described vascular cell adhesion molecule-1 (VCAM-1) in human kidney, using the anti-VCAM-1 monoclonal antibody 1.4C3. In normal control tissue VCAM-1 was present on some (but not all) parietal epithelial cells lining Bowman's capsule. Forty-nine of fifty clinical biopsy specimens were characterised by the additional presence of VCAM-1 on proximal tubular cells. This was most marked in biopsies of patients with interstitial nephritis or systemic vasculitis with crescentic nephritis, but was also observed in biopsies with minimal change, IgA or lupus nephropathy, or from patients with diabetic nephropathy, amyloid, or gout. Proximal tubule VCAM-1 correlated significantly with the number of transferrin-receptor-positive leukocytes (r = 0.607, p less than 0.0001) in the interstitium, but not with expression of HLA-DR by tubular cells. Surprisingly, VCAM-1 was not observed on vascular endothelial cells in these biopsies, even in the presence of a marked infiltrate; this contrasts with other tissues (e.g. skin and synovium). The presence of VCAM-1 on tubular cells in the inflamed kidney indicates the potential for these cells to interact with mononuclear cells, either as accessory cells or as cytotoxic targets. The unexpected absence of VCAM-1 in renal vascular endothelial cells suggests local differences in the endothelial cells of this organ.
 ...
PMID:Expression of VCAM-1 in the normal and diseased kidney. 172 89

A 34-year-old female with an 8-month history of systemic lupus erythematosus and intermittent naproxen use presented with acute oliguric renal failure, hypoalbuminemia, 4+ proteinuria, and an active urinary sediment. The clinical picture suggested a rapidly progressive lupus glomerulonephritis. Renal biopsy, however, demonstrated chronic, active interstitial nephritis without evidence of immune deposits by immunofluorescence or electron microscopy. Nonsclerotic glomeruli revealed diffuse foot process fusion without cellular proliferation. These findings were consistent with nonsteroidal anti-inflammatory drug induced nephropathy. Discontinuation of naproxen and institution of corticosteroid therapy was followed by improvement in renal function and remission of nephrotic syndrome. This case represents the first report of nonsteroidal antiinflammatory drug nephropathy associated with systemic lupus erythematosus.
 ...
PMID:Naproxen-induced nephropathy in systemic lupus erythematosus. 217 59

Sera from 35 patients with biopsy-proven diffuse proliferative (WHO class IV) or membranous (WHO class V) lupus nephritis were analyzed for the presence and size of circulating immune complexes. Elevations of the C1q solid-phase assay (C1qSP) for immune complexes were found in sera from all patients with diffuse proliferative nephritis, with a mean +/- 1 SEM of 166.8 +/- 42.0 micrograms/AHG-equivalents/ml serum, and in 71.4% of the patients with membranous nephritis (83.1 +/- 26.7, p = 0.06). Using the WHO criteria for subclasses of membranous lupus nephritis, we also designated renal biopsies as nonproliferative (WHO classes Va and Vb) or proliferative (WHO classes IV and Vc). Employing the latter groupings, we observed significant differences between C1qSP results of patients with nonproliferative (30.3 +/- 8.8) and proliferative (172.8 +/- 36.8, p less than 0.001) lupus nephritis. These data suggest that the presence of C1q-binding material in serum is pathophysiologically related to proliferative glomerular lesions, and that levels of C1qSP binding reflect renal lesions in SLE patients. Sucrose density gradient ultracentrifugation was performed on each serum, and gradient fractions analyzed for C1qSP-binding and total IgG, using techniques to minimize losses of immune complexes. The predominant peak of C1qSP activity sedimented with the 6.6S monomeric IgG. The 6.6S C1q-binding IgG was increased only in 1 of 10 patients with membranous lupus nephritis without proliferative changes, and was elevated in 16 of 25 patients with proliferative lesions (WHO classes IV and Vc). A significant negative correlation was found between the presence of this C1q-binding material and subepithelial electron-dense deposits, suggesting that the presence of this material contributed to the absence of subepithelial immune deposits. Large-molecular-weight C1qSP-binding material was also present, mainly in sera from patients with proliferative lesions. Furthermore, highly positive correlations were found between immune deposits in interstitial blood vessels and peritubular areas, and the concentrations of C1qSP-binding IgG and rapidly sedimenting IgG in density gradient analysis. Overall, these findings are consistent with the hypotheses that circulating immune complexes contribute to the pathogenesis of glomerulonephritis and interstitial nephritis in patients with SLE, and that 6.6S C1q-binding IgG plays a role in the proliferative lesions of lupus glomerulonephritis.
 ...
PMID:Relationship between renal pathology and the size of circulating immune complexes in patients with systemic lupus erythematosus. 310 94

Predominant interstitial nephritis is a rare manifestation of systemic lupus erythematosus. Only seven cases have been reported in the literature. Owing to the rarity of this entity, the natural history of predominant interstitial nephritis in lupus has not been adequately recorded and an appropriate therapeutic approach has yet to be defined. In this report we present the case of a 25 year old woman with active systemic lupus erythematosus complicated by kidney failure and renal tubular acidosis due to predominant interstitial nephritis. We describe the course of her disease over a three year period. Seven additional patients with systemic lupus erythematosus and predominant interstitial nephritis are reviewed.
 ...
PMID:Chronic predominant interstitial nephritis in a patient with systemic lupus erythematosus: a follow up of three years and review of the literature. 331 Sep 27

A concept of the pathogenesis of tubular interstitial nephritis (TIN) is presented, based on histologic, immunohistologic and electromicroscopic investigations on 61 patients with glomerulonephritis, lupus erythematodes and rheumatoid arthritis. The pathogenic model is a hypersensitivity reaction which leads to alterations in the tubular basement membrane (TBM) and results in changes in the TBM and secondary damage to stroma, vessels and tubular cells. The findings change depending on the stage, reflecting the transition from an acute to a chronic process. In acute TIN which is generally a drug allergy, the dominant characteristic of the inflammatory process allows the reaction to be categorized in edematous (72%), cellular (23%) and tubular necrotic (5%) types. The cellular types show 4 subdivisions: plasma cellular, eosinophil-granulocytic, lymphohistiocytic and granulomatous. Chronic TIN is in particular characterized through the destruction of the TBM, dystrophy and atrophy of the tubules as well as their degeneration, lymphohistiocytic infiltrates and sclerotic stroma reactions. A distinction is made between cellular destructive and atrophic-sclerotic types. At view of the etiology and pathogenesis a distinction should be made between an infectious and non-infectious TIN and further by the character of the immunoreaction, into a primary and secondary form. If there glomerular changes are present and there is evidence of an immune phenomenon in the glomeruli and TBM we recommend the use of the term glomerulo-tubulo-interstitial nephritis.
 ...
PMID:[Tubulointerstitial nephritis]. 356 28

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.
 ...
PMID:Renal disease associated with HIV infection: a multicentric study of 60 patients from Paris hospitals. 838 28

Kidney tubule cells (KTC) are targets of T lymphocyte injury during allograft rejection and interstitial nephritis. KTC process and present self- and foreign Ags for immune recognition by CD4+ T cells in vivo and in vitro. However, it is not known whether KTC can provide the costimulatory signal required to fully activate CD4+ T cells. Using the MRL/MpJ fas<lpr> model of lupus interstitial nephritis, we found that KTC did not express the costimulators B7-1 or B7-2. Nevertheless, KTC from both normal and systemically infected mice provided non-B7 costimulation to splenic CD4+ T cells. T cell proliferation was blocked by mAbs binding intercellular adhesion molecule-1 (ICAM-1) but not by mAb or fusion proteins binding B7-1, B7-2, heat-stable Ag, or vascular cell adhesion molecule-1. Importantly, ICAM-1 expression was necessary but not sufficient to provide costimulation. The transformed KTC line D3.B7- expressed high levels of ICAM-1 but did not provide costimulation. Interestingly, KTC provided costimulation to splenic T cells but not to a Th1 clone. These results show that freshly isolated KTC can provide non-B7 costimulation to splenic T cells via an unidentified costimulator and ICAM-1. Furthermore, these experiments demonstrate the complex nature of T cell activation and show that at least for splenic T cells, three or more signals may be required for full activation on live APC.
 ...
PMID:Intercellular adhesion molecule-1 is necessary but not sufficient to activate CD4+ T cells. Discovery of a novel costimulator on kidney tubule cells. 862 99

Humoral and end-organ parameters of autoimmunity were investigated in LG/J mice, which have traditionally been considered normal, non-diseased animals. Surprisingly, LG/J mice were found to possess autoantibodies, including antinuclear antibodies and rheumatoid factor, and to develop renal disease, including glomerulonephritis, interstitial nephritis, and perivasculitis, but not hepatic or cutaneous disease. In contrast, age-matched, identically-housed control animals failed to develop autoantibodies or end-organ disease. These findings have complications for the genetic study of lupus erythematosus in the MRL murine model, which derives heavily from the LG/J background. Thus, the LG/J strain may provide a useful model in the analysis of autoimmunity.
 ...
PMID:Systemic autoimmunity in LG/J mice. 902 95


1 2 3 Next >>