Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nephrotic syndrome in minimal change lipoid nephrosis and focal segmental glomerulosclerosis may be due to alteration of glomerular anionic sites by a lymphokine. Six adults with nephrotic syndrome who were resistant to treatment with corticosteroids and immunosuppressants were treated with cyclosporin A. In three patients with minimal change lipoid nephrosis who had been nephrotic for 3.5 to 23 years proteinuria resolved within 12 to 42 days. Subsequently, these patients became dependent on cyclosporin A. In three patients with focal segmental glomerulosclerosis who had been nephrotic for four to six years mean (SD) 24 hour urinary protein decreased from 14.7 (8.4) g to 3.6 (0.6) g within 20 to 25 days, serum albumin concentration rose, and oedema subsided. One patient died of myocardial infarction when still in partial remission after 11 weeks' treatment. Two patients remained proteinuric despite continuing treatment with cyclosporin A, but control of sodium balance was easy and serum albumin concentrations remained higher than without cyclosporin A. In all patients renal function improved during treatment. These preliminary results show that cyclosporin A may be effective in the treatment of patients with nephrotic syndrome that resists every other form of treatment and especially in the treatment of those with minimal change lipoid nephrosis. The results are in keeping with a T lymphocyte mediated mechanism of minimal change lipoid nephrosis and focal segmental glomerulosclerosis, but they also suggest that minimal change lipoid nephrosis and focal segmental glomerulosclerosis are separate entities.
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PMID:Remission of idiopathic nephrotic syndrome after treatment with cyclosporin A. 308 43

Patients with minimal change nephrotic syndrome (MCNS) frequently have suppressed in vivo and in vitro immune responsiveness of uncertain etiology. Because increased suppressor cell activity has been associated with this disease, urines from MCNS patients were screened for activity of the lymphokine soluble immune response suppressor (SIRS), a product of concanavalin A- or interferon-activated suppressor T cells. Urines from untreated MCNS patients suppressed polyclonal plaque-forming cell responses of cultured splenocytes. This suppressive activity was identified as human SIRS by the following functional and physical criteria: molecular weight estimated by gel filtration; kinetics of suppression; inhibition of suppression by catalase, levamisole, and 2-mercaptoethanol; abrogation of activity by acid or protease treatment; elution pattern on high performance liquid chromatography; and cross-reactivity with monoclonal antimurine SIRS antibodies. Suppressive activity disappeared from urine after initiation of treatment but before remission of symptoms. Urines were tested from 11 patients with MCNS, all of whom excreted SIRS. In addition, two nephrotic patients with acute glomerulonephritis and three nephrotic patients with membranoproliferative disease excreted SIRS, but other nephrotics and all nonnephrotic patients did not. These results indicate that excretion of SIRS occurs in certain cases of nephrotic syndrome and that the presence of SIRS in the urine is not accounted for solely by the presence of proteinuria or nephrosis. Serum from four nephrotic patients also contained SIRS, whereas neither serum nor urine from six normal subjects contained SIRS activity. The systemic presence of SIRS in these four patients, and the identification of SIRS in urines from a larger group of patients, suggest a possible role for SIRS in the suppressed immune responses often found in nephrotic syndrome.
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PMID:Identification of the lymphokine soluble immune response suppressor in urine of nephrotic children. 401 84

A 44-year-old man was diagnosed with cutaneous T-cell lymphoma characterized by a proliferation of CD4-positive cells. In response to alpha-interferon therapy, he experienced rapid regression of his cutaneous disease. This improvement was associated with development of renal failure, characterized by nephrotic-range proteinuria with interstitial nephritis and minimal-change nephropathy. The remarkable finding of renal biopsy was marked proliferation of visceral epithelial cells (podocytes). Renal disease improved significantly in response to discontinuation of interferon and initiation of prednisone therapy. Nephrotic range proteinuria regressed, but never completely resolved. This case is illustrative of the probable role for lymphokine-mediated nephrotoxicity in the setting of lymphoproliferative disease.
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PMID:Minimal-change glomerulopathy and glomerular visceral epithelial hyperplasia associated with alpha-interferon therapy for cutaneous T-cell lymphoma. 791 55

Small amounts of amyloid in kidney biopsy specimens may be missed on routine examination unless specifically targeted. Occasionally, this oversight results in a diagnosis of minimal change glomerulonephritis (MCGN). This misdiagnosis may be facilitated by the fact that typical "minimal changes" with flattening and effacement of the epithelial foot processes can be found in capillary loops directly affected by amyloid deposition as well as in capillary loops of glomeruli with only mild amyloid deposition in the mesangium. Repeatedly, the diagnosis of MCGN had to be corrected to renal amyloidosis when re-examination by special techniques succeeded in detecting even small amounts of amyloid fibrils. We present the case of a previously healthy 49-year-old man who suddenly developed nephrotic syndrome. A first renal biopsy showed MCGN. Proteinuria remained refractory to immunosuppressive treatments, and creatinine clearance deteriorated rapidly. Two years later, a repeat renal biopsy showed AL-amyloidosis. In this case, re-examination of the first biopsy in the light of the final diagnosis again did not show any deposition of amyloid fibrils. We suspect that proteinuria and epithelial podocyte changes in amyloidosis are caused by factors other than deposition of amyloid fibrils itself. Possibly a cytokine release during the early fibril formation leads to abnormalities even before the typical structural changes of renal amyloidosis can be detected. This is analogous to the hypothesis of a circulating factor that leads to proteinuria in focal segmental glomerulosclerosis or the speculation of altered lymphokine expression associated with the development of MCGN in Hodgkin's disease.
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PMID:AL-amyloidosis of the kidney initially presenting as minimal change glomerulonephritis. 1097 97

Myasthenia gravis is caused by antibodies against acetylcholine receptors and is treated with inhibition or elimination of antibody production. We report a 58-year-old woman who had been suffering from myasthenia gravis and underwent thymectomy in July 1995. Her myasthenic symptoms improved with immunosuppressive treatment using corticosteroid(100 mg/day) and azathioprine(100 mg/day). However she presented edema with massive proteinuria(7.54 g/day) and was admitted to our hospital on July 1997. She was diagnosed as having nephrotic syndrome and a renal biopsy was performed. The histological findings showed minimal change nephrotic syndrome. After pulse therapy with methylprednisolone(1 g/day x 3 days) following oral administration of prednisolone(60 mg/day), proteinuria disappeared after one month. Nephrotic syndrome is a rare complication in patients with myasthenia gravis. The increase in lymphokine production caused by thymectomy may be closely associated with the occurrence of nephrotic syndrome in spite of intensive immunosuppressive treatment in the present case. In this report, we also summarized reported cases of minimal change nephrotic syndrome with thymoma and myasthenia gravis.
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PMID:[A case of myasthenia gravis, who developed minimal change nephrotic syndrome during immunosuppressive therapy after thymectomy]. 1099 21

The concept that increased glomerular albumin permeability in steroid-resistant nephrotic syndrome is induced by circulating humoral factors is not new. Zimmermann (1) was among the first to demonstrate that serum from a renal transplant patient with recurrent focal segmental glomerulosclerosis (FSGS) could provoke increased albumin excretion when infused in the aorta of intact rats. Unfortunately, the experiment was not easily reproducible, and the possibility that human serum could induce serum sickness in rats was a serious limitation of the original experiment. We now know that inhibitors of permeability activity are present in both normal human and rat serum (see below), which explains the difficulty in replicating the disease in intact animals. In 1974 Shalhoub (2) theorized that a disordered clone of T lymphocytes, present in both minimal change disease and FSGS, secreted a circulating lymphokine "toxic" to the glomerular barrier. In support of this hypothesis, Koyama et al (3) formed hybridomas from T cells from four patients with minimal change disease and three control subjects. The hybridomas of the patients produced a substance that induced proteinuria when injected intravenously into normal rats. However, the study utilized stimulated and not quiescent T cells, and therefore the relevance to the pathogenesis of FSGS is unknown. Hoyer and colleagues first described recurrence of idiopathic nephrotic syndrome after renal transplantation in 1972 (4). Numerous subsequent reports have established the rate of recurrence as being about 30%. Timely plasmapheresis associated with aggressive immunosuppression resolves the proteinuria and disease progression in a large proportion of cases (5). FSGS not only recurs after renal transplantation, but the diseased kidney can also recover when kept protected from the pathological milieu. Rea et al (6) demonstrated that kidneys from a donor with FSGS transplanted into two uremic recipients were free from proteinuria, and that renal function was normal after one year. Ethical and legal considerations aside, recurrence of FSGS after transplantation is strong evidence supporting the role of a humoral factor in the pathogenesis of the disease.
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PMID:Humoral permeability factors in the nephrotic syndrome: a compendium and prospectus. 1179 45

Nephrotic focal segmental glomerulosclerosis (FSGS) represents a difficult therapeutic challenge. FSGS has long been considered a subset of idiopathic nephrotic syndrome, lumping together FSGS and minimal change disease (MCD). The time-honored 'Shalhoub hypothesis' has led to treating FSGS as a T-cell-driven condition in which a lymphokine, considered without proof as being the 'glomerular permeability factor,' induces proteinuria and podocyte functional and structural derangement. This has led to trying, in addition to steroids, every new drug marketed in the field of organ transplantation, first cyclosporine (CsA) and then other immunophilin modulators. The fact that alkylating agents and mycophenolate mofetil have obtained a poor and inconstant favorable effect, and that rituximab may obtain remissions, although inconstantly, has not led to reconsidering the T-cell hypothesis. This wrong thinking has fostered innumerable, mostly uncontrolled, treatment trials with various immunosuppressive agents. In fact, clinicians have not considered the fact that some but not all immunophilin modulators may be effective as nonspecific antiproteinuric agents, rather than as immunosuppressive drugs, and that treatment success does not exclude a non-immunologic pathophysiology. Recent findings on the mode of action of CsA and FK-506 have lent support to this concept. This review should be considered as a plea to reconsider the pathogenesis of nephrotic FSGS, applying all efforts to the identification of the factor, or factors, responsible for nephrotic FSGS, and to fund treatment to counteract the 'factor,' rather than pursuing costly and non-evidence-based immunosuppressive therapeutic trials.
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PMID:Treatment of focal segmental glomerulosclerosis with immunophilin modulation: when did we stop thinking about pathogenesis? 2007 61

Severe forms of the nephrotic syndrome are, by definition, steroid-resistant or strongly steroid-dependent. Steroid-resistant forms have two causes. The first is T and B lymphocyte dysfunction, which may result in the production of a lymphokine which increases the permeability of the glomerular filtration barrier. The second is mutation of genes that encode proteins involved in establishing and maintaining the glomerular filtration barrier. Mycophenolate mofetil and rituximab are effective new treatments for severe steroid-dependent nephrotic syndromes. The beneficial effect of cyclosporine on proteinuria may result from stabilization of the actin cytoskeleton in podocytes.
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PMID:[Management of severe idiopathic nephrotic syndrome in children]. 2066 37


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