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)

A 17-year-old woman was admitted because of proteinuria, microhematuria and liver dysfunction with increased antinuclear antibody and anti-myeloperoxidase antibody (MPO-ANCA). Fourteen months' previously, urinalysis and liver function showed normal range. At that time she suffered from tachycardia and weight reduction, diagnosed as Graves' disease, she was given propylthiouracil for treatment of her Graves' disease. The histological finding of renal biopsy was compatible with minor glomerular abnormalities. Liver biopsy finding was compatible with autoimmune hepatitis. After we had administered prednisolone, liver function returned to normal range and urine protein became negative. Then we performed subtotal thyroidectomy, and she was not given propylthiouracil. MPO-ANCA decreased gradually.
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PMID:Graves' disease accompanied by anti-myeloperoxidase antibody-related nephropathy and autoimmune hepatitis. 1528 91

Granulopoiesis-related genes are distinctively upregulated in peripheral leukocytes of patients with antineutrophil cytoplasmic autoantibodies (ANCA)-associated glomerulonephritis. Affymetrix microarrays identified the upregulation of nine neutrophilic primary granule genes, including myeloperoxidase (MPO) and proteinase 3 (PR3), plus five secondary granule genes. Coordinate expression of granulocyte maturation marker CD35, measured by TaqMan PCR, and positive in situ staining for PR3 transcripts in polymorphic neutrophils and monocytes indicate that these genes are expressed in "mature" cells. Increased transcripts correlated with disease activity and absolute neutrophil values but not with "left shift," drug regimen, cytokine levels, hematuria, proteinuria, ANCA titer, serum creatinine, gender, or age. Upregulation of PR3 and MPO transcripts was specifically associated with ANCA disease (n = 56) as these changes were not detected in patients with ESRD (n = 25) or systemic lupus erythematosus (n = 17), as determined by TaqMan PCR. This is the first report of this phenomenon in nonneoplastic cells. The data raise the hypothesis that, in addition to the presence of anti-MPO or anti-PR3 autoantibodies, a second critical component in the cause of this disease is the reactivation of once-silenced genes leading to increased antigen availability.
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PMID:Circumvention of normal constraints on granule protein gene expression in peripheral blood neutrophils and monocytes of patients with antineutrophil cytoplasmic autoantibody-associated glomerulonephritis. 1528 96

Infiltrated neutrophils is believed to contribute to the progression of vasculitis. In particular, myeloperoxidase (MPO)-specific antibodies against neutrophils, anti-neutrophil cytoplasmic antibodies (MPO-ANCA) is involved in the development of vasculitis microscopic polyangiitis etc. In Japan a higher percentage of MPO-ANCA than that in Europe has been reported In addition, we showed a correlation of MPO-ANCA epitopes of Kawasaki disease patients by 47% with that of mothers'. On the other hand, mice having CADS/CAWS-induced vasculitis is a good model for the analysis of the production of MPO-ANCA. We have clarified that MPO is a major antigen for MPO-ANCA production using MPO KO mice. We also investigated the role of activated neutrophils in nephritis renal lesions using SCG/Kj mice. In the phase of nephritis with low grade of proteinuria, the spontaneous release of MPO from peripheral neutrophils increased, indicating that neutrophils are activated and contribute to the development of active crescentic lesion in SCG/Kj mice.
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PMID:Contribution of myeloperoxidase in vasculitis development. 1550 59

Dent's disease is an hereditary renal tubular disorder characterized by low-molecular-weight (LMW) proteinuria, hypercalciuria and nephrolithiasis. The disease is due to mutations of CLC-5, a member of the family of voltage-gated CLC chloride channels. CLC-5 is distributed in cells lining the proximal tubule (PT) of the kidney, where it co-localizes with albumin-containing endocytic vesicles that form part of the receptor-mediated endocytic pathway that mediates the reabsorption of low-molecular-weight (LMW) proteins filtered at the glomerular level. Since progression along the endocytic apparatus requires endosomal acidification, it has been suggested that dysfunction of CLC-5 in endosomes may lead to inefficient reabsorption of LMW proteins and dysfunction of PT cells. Investigations conducted in a CLC-5 knockout (KO) mouse model harbouring all the characteristic renal tubular defects of Dent's disease showed a severe impairment of endocytosis by PT cells, such that the endocytic tracer peroxidase was poorly transferred into early endocytic vesicles. These data demonstrated that an impairment of receptor-mediated endocytosis in PT cells is the basis for the defective uptake of LMW proteins in patients with Dent's disease. The endocytosis and processing of LMW proteins involves the multiligand tandem receptors, megalin and cubilin, that are abundantly expressed at the brush border of PT cells. The characterization of the endocytic defect in CLC-5 KO mice revealed that ligands of both megalin and cubilin were affected, whereas a decrease in total kidney content of megalin and cubilin at the protein level was detected. Using analytical subcellular fractionation and quantitative immunogold labelling, we demonstrated a selective disappearance of megalin and cubilin at the brush border of PT cells. These observations allowed us to conclude that defective protein endocytosis linked to CLC-5 inactivation is due to a major and selective loss of megalin and cubilin at the brush border, reflecting a trafficking defect in renal PT cells. These results improve our understanding of Dent's disease, taken as a paradigm for renal Fanconi syndrome and nephrolithiasis, and demonstrate multiple roles for CLC-5 in the kidney. These studies also provided insights in important functions such as apical endocytosis, handling of proteins by renal tubular cells, calcium metabolism, and urinary acidification.
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PMID:Chloride channels and endocytosis: new insights from Dent's disease and CLC-5 knockout mice. 1561 95

Dent's disease is a hereditary renal tubular disorder characterized by low-molecular weight (LMW) proteinuria, hypercalciuria and nephrolithiasis. The disease is due to mutations of ClC-5, a member of the family of voltage-gated CLC chloride channels. ClC-5 is expressed in part in cells lining the proximal tubule (PT) of the kidney, where it colocalizes with albumin-containing endocytic vesicles belonging to the receptor-mediated endocytic pathway that ensures efficient reabsorption of ultrafiltrated LMW proteins. Since progression along the endocytic apparatus requires endosomal acidification, it has been suggested that dysfunction of ClC-5 in endosomes may lead to inefficient reabsorption of LMW proteins and dysfunction of PT cells. Analysis of a ClC-5 knockout (KO) mouse model, displaying all the characteristic renal tubular defects of Dent's disease, showed evidence of a severe LMW proteinuria. Cytochemical studies with the endocytic tracer, peroxidase, showed poor transfer into early endocytic vesicles, suggesting that impairment of receptor-mediated endocytosis in PT cells is the basis for the defective uptake of LMW proteins in patients with Dent's disease. Endocytosis and processing of LMW proteins involve the multiligand tandem receptors, megalin and cubilin, that are abundantly expressed at the brush border of PT cells. Characterization of the endocytic defect in ClC-5 KO mice revealed that ligands of both megalin and cubilin were affected. The total kidney content of megalin and especially cubilin at the protein level was decreased but, more importantly, using analytical subcellular fractionation and quantitative immunogold labelling we demonstrated a selective disappearance of megalin and cubilin at the brush border of PT cells. These observations allowed us to conclude that defective protein endocytosis linked to ClC-5 inactivation is due at least in part to a major and selective loss of megalin and cubilin at the brush border, reflecting a trafficking defect in renal PT cells. These results improve our understanding of Dent's disease, taken as a paradigm for renal Fanconi syndrome and nephrolithiasis, and demonstrate multiple roles for ClC-5 in the kidney. These studies also provided insights into important functions such as apical endocytosis, handling of proteins by renal tubular cells, calcium metabolism, and urinary acidification.
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PMID:Chloride channels and endocytosis: new insights from Dent's disease and ClC-5 knockout mice. 1563 24

We report on successful induction of remission in a patient with necrotizing crescentic glomerulonephritis associated with myeloperoxidase-antineutrophil-cytoplasm antibodies by primary use of the anti-tumor necrosis factor (TNF)-alpha chimeric monoclonal antibody infliximab in combination with corticosteroids only. The standard treatment containing cyclophosphamide has reduced the former high mortality from systemic vasculitides. However, the toxicity of this alkylating agent limits its long-term use. As TNF-alpha has been shown to play a central pathogenic role in vasculitis as well as in crescentic glomerulonephritis, anti-TNF-alpha treatment in combination with cyclophosphamide has been found to be effective in therapy-resistant vasculitis. Previous reports on TNF-alpha-blocking therapies without additional cyclophosphamide did not include patients with active and severe crescentic glomerulonephritis. As our patient refused cyclophosphamide, he was given four infusions of infliximab (4 mg/kg on weeks 0, 2, 6 and 10) and methylprednisolone pulses (1 g on days 1-3), followed by daily oral prednisolone (starting with 2 mg/kg and tapering down to 5 mg daily within 3 months). After 12 weeks, control biopsy demonstrated lack of active glomerular inflammation while initially reduced renal function (creatinine 271 versus 172 mol/l, clearance 26 versus 62 ml/min) and proteinuria (2.4 versus 1.0 g/d) improved. Under remission maintenance therapy with azathioprine and prednisolone, the patient showed no relapses during a 1-year follow-up. Finally we demonstrate that there might be patients with crescentic glomerulonephritis who do not require therapy with alkylating substances and that less toxic agents such as the TNF-alpha-blocking monoclonal antibody infliximab could play a role in future primary treatment of crescentic glomerulonephritis.
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PMID:Crescentic glomerulonephritis associated with myeloperoxidase-antineutrophil-cytoplasmic antibodies: first report on the efficacy of primary anti-TNF-alpha treatment. 1564 40

Small vessel vasculitides, usually associated with positive antineutrophil cytoplasmic antibodies (ANCA(+)) can cause pulmonary-renal syndrome (PRS). Data from 22 patients, (19 males), aged 28-76 yrs (mean 55), with PRS were analyzed retrospectively. Renal function was estimated at presentation, 1 month after treatment initiation and at the end of follow-up (mean 4.4 +/- 3.3 yrs). Thirteen out of 22 patients had PR3 (+) ANCA and 9/22 patients had MPO (+) ANCA. Mean serum creatinine (Cr) at diagnosis was 6.6 +/- 4.4 mg/dL (M +/- SD) and proteinuria 1.6 +/- 1.4 g/24 hr (M +/- SD). During the 1st month of treatment with corticosteroids and cyclophosphamide, renal function improved in 12 patients (54.5%) (serum Cr from 8.5 +/- 4.5 to 4.3 +/- 2.3 mg/dL, p=0.001) remaining stable thereafter, and renal function deteriorated in nine patients (41%) (serum Cr from 4.1 +/- 3 to 6.5 +/- 2.9 mg/dL, p=0.03); one patient (4.5%) died because of sepsis. At the end of the study, 11/22 patients (50%) had died, eight patients of these (73%) because of respiratory failure, three patients (13.6%) reached end-stage renal disease (ESRD), five patients (36.4%) remained stable, but with impaired renal function and finally three patients (13.6%) improved, achieving almost normal renal function. In multiple regression analysis, factors contributing to final serum Cr were: dialysis dependency at the time of diagnosis p=0.01, initial proteinuria p<0.0001, and percentage of cellular crescents p=0.003. Main differences between PR3 and MPO (+) patients were the chest CT findings (bilateral nodules in PR3 (+) and "ground glass" or fibrosis in MPO (+) patients) and the renal function improvement rate after treatment initiation (rapid decline in serum Cr in PR3 (+) patients). In conclusion, PRS with ANCA (+) is associated with increased mortality. If renal function improves during the 1st month of treatment, it usually remains stable thereafter. The presence of PR3-ANCA is associated with an early response to treatment, while MPO-ANCA vasculits seems to necessitate prolonged treatment.
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PMID:Factors influencing patient survival and renal function outcome in pulmonary-renal syndrome associated with ANCA (+) vasculitis: a single-center experience. 1577 21

The association of renal disease and autoimmune thyroid disorders has been reported previously. Renal findings associated with autoimmune thyroiditis present more commonly as proteinuria ranging from mild to nephrotic levels. We report here two adolescent girls with hyperthyroidism associated with transient proteinuria correlated with thyroid hormone levels. They had positive antithyroid peroxidase and antithyroglobulin antibodies. Ultrasonographic and scintigraphic findings of the thyroid gland were consistent with Graves' disease in both. Their renal functions were normal except proteinuria (daily protein excretion of 13.5 mg/m2/h in patient 1 and 11 mg/m2/h in patient 2). When they became euthyroid on antithyroid treatment, proteinuria decreased without associated hematuria and/or hypertension. In conclusion, patients with autoimmune thyroid disease should be assessed for the possibility of proteinuria and the etiological investigation of proteinuria should include evaluation of thyroid functions.
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PMID:Autoimmune thyroiditis with associated proteinuria: report of two patients. 1581 12

A 50-year-old woman was admitted because of high fever and fatigue. Proteinuria, hematuria, and elevated BUN (47.8 mg/dl) and creatinine (3.4 mg/dl) suggested rapidly progressive glomerulonephritis. The serological study revealed all negative results for rheumatoid factor, antinuclear antibody, serum cryoglobulins, MPO-ANCA, PR3-ANCA, and anti-streptolysin O. Antiglomerular basement membrane (GBM) antibody, as assessed by ELISA, was 11 EU (normal, <10). Kidney biopsy on the eighth hospital day demonstrated pauci-immune-type crescentic glomerulonephritis without ANCA. Methylprednisolone pulse therapy (500 mg/day, 3 days) and 45 mg/day prednisolone orally were started. At 3 weeks after kidney biopsy, the anti-GBM antibody value increased from 11 EU/ml to 116 EU/ml, and MPO and PR3-ANCA were still negative. HLA type was DR8 and DR 15(2), with a genotype of HLA-DRB1*08021 and HLA-DRB1*15011. The present case suggests that HLA-DR15 plays an important role on antibody production against alpha 3(IV) NC1 autoantigen after severe nephritis or tissue damage.
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PMID:The increase of antiglomerular basement membrane antibody following pauci-immune-type crescentic glomerulonephritis. 1583 Feb 77

A 71-year-old man was admitted with low-grade fever, a high titer of CRP and ANCA. He was diagnosed as MPO-ANCA-associated vasculitis. On admission, his renal function was normal. Proteinuria and extra renal symptoms were not recognized. Only hematuria and hyaline cast were detected. A high titer of CRP and MPO-ANCA persisted. After obtaining informed consent, a renal biopsy was performed, revealing cellular crescentic glomerulonephritis and necrotizing vasculitis. The findings of the renal biopsy indicated an early phase of ANCA-associated nephritis. After MPSL pulse therapy, renal function was in the nomal range and proteinuria and hematuria disappeared. This present case demonstrated that early diagnosis and treatment are very important to sustain normal renal function if a high titer of MPO-ANCA is recognized in an elderly person without proteinuria.
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PMID:[Case of ANCA-associated glomerulonephritis detected at an early phase]. 1613 Apr 9


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