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

In minimal change nephrosis (MCN), proteinuria is associated with structural changes of the glomerular visceral epithelial cells (GVEC). The occurrence of MCN has been associated with 2 lymphocyte-dependent conditions. To examine a direct role for type 2 cytokines in GVEC injury, the expression of interleukin (IL)-4/IL-13 receptors by GVEC and direct effects of IL-4 and IL-13 on GVEC were studied. Reverse transcription-PCR showed that isolated human and rat glomeruli and cultured human and rat GVEC expressed mRNA for IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2. Protein expression of [L-4Ralpha and IL-13Ralpha2 by GVEC in human kidney biopsies and by cultured human GVEC was detected by immunohistochemistry. Western blotting demonstrated phosphorylation of STAT6 in cultured GVEC upon incubation with IL-4 or IL-13. This indicated signal transduction via the heterodimeric receptor complex IL-4R2, which is composed of the IL-4Ralpha and the IL-13Ralpha1. Direct effects on GVEC function were examined in monolayer experiments. IL-4 and IL-13 dose-dependently decreased transepithelial electrical resistance of monolayers of rat GVEC to approximately 30 and 40% of baseline values, respectively. The transepithelial electrical resistance decrease was associated with a significant increase in short-circuit current, whereas no changes were observed in the transmonolayer flux of the macromolecules horseradish peroxidase (molecular weight, 44 kD) and 14C-mannitol (molecular weight, 182 Da). No changes in cell structure were observed with electron microscopy. It is concluded that by binding to specific IL-4/ IL-13 receptors, IL-4 and IL-13 can exert specific effects on GVEC function, which could be of pathogenetic relevance for glomerular injury in MCN.
 ...
PMID:Interleukin-4 and interleukin-13 act on glomerular visceral epithelial cells. 1070 65

A 75-year-old woman was admitted to our hospital because of high fever and appetite loss. A chest roentgenogram and computed tomographic scans revealed pleural effusion without obvious infitrative or interstitial shadows in both lung fields. Laboratory data showed microhematuria, proteinuria, and telescoped sediment with a moderate increase in C-reactive protein, suggestive of acute glomerulonephritis. Because infectious pleuritis, was initially suspected, the patient was treated with antibiotics. However, her general condition deteriorated, and the right pleural effusion increased. Levels of myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA) in serum and pleural effusion were markedly elevated, yielding a conclusive diagnosis of MPO-ANCA-related vasculitis, especially microscopic polyangitis (MPA). The Patient was immediately treated treated with prednisolone, cyclophosphamide, and plasma exchange. Several weeks later, her general condition dramatically improved, and the level of MPO-ANCA in serum markedly decreased. In addition, the pleural effusion completely disappeared. Unfortunately, the patient eventually died of opportunistic infections (MRSA-pneumonia and Aspergillus-pneumonia) 6 months after admission. This was a unique case of MPA associated with pleuritis without interstitial pneumonia or alveolar hemorrhage.
 ...
PMID:[Microscopic polyangitis with pleuritis as the only pulmonary complication]. 1084 5

We reported 2 children with suspected primary vasculitis of mesenteric vessels. Both children were admitted to our hospital with the complaints of abdominal pain, bloody stool or diarrhea. Laboratory examination simultaneously revealed leukocytosis with dominant neutrophils, positive CRP, and hypoalbuminemia. Although prothrombin time and activated partial thromboplastin time were within normal limits, the increased levels of FDP-E, D-dimer, and von Willebrand factor activity were observed, which suggested the endothelial cell activation and the coagulation/fibrinolysis system activation. Abdominal echography and CT scanning demonstrated the edematous thickening of intestinal or colon walls probably due to the vasculitic permeability changes of mesenteric artery. During the disease courses, skin rash, bleeding tendency, arthritis and proteinuria were not observed, and no autoantibodies including anti-nuclear antibody, anti-DNA antibody, and myeloperoxidase-antineutrophil cytoplasmic antibody, were detected. Taken together, we suspected these children as restricted vasculitis of mesenteric vessels. Intravenous prednisolone was administrated, and the clinical and laboratory abnormalities recovered completely within 2 weeks. Thus, we suggested that the leukocyte counts, CRP, and the determination of von Willebrand factor and coagulation/fibrinolysis study accompanied with X-ray, echography, and CT scanning will be useful for the early diagnosis of vasculitis before the pathologic and irreversible vascular damage are demonstrated.
 ...
PMID:[Two children with suspected primary vasculitis of mesenteric vessels--a case report]. 1086 31

We report a case of hepatitis C virus-associated glomerulonephropathy presenting with MPO-ANCA-positive, rapidly progressive glomerulonephritis(RPGN). A 60-year-old woman was admitted to our hospital for evaluation of RPGN. Laboratory evaluation revealed microhematuria, proteinuria(800 mg/day), anemia, renal failure(blood urea nitrogen 27 mg/dl, serum creatinine 2.2 mg/dl), cryoglobulinemia, hypocomplementemia, positive MPO-ANCA(232 EU), and hepatitis C virus infection(GOT 58 IU/l, GPT 38IU/l, HCV-RNA(PCR) 1,200 kcopy/ml, serotype 1). After admission, the patient's renal function and anemia deteriorated rapidly, then prednisolone(30 mg/day) was started. After treatment her renal function gradually improved, then a renal and liver biopsy was performed. The renal biopsy revealed six sclerosing fibrous crescentic glomeruli in twelve glomeruli. Immunofluorescent examination revealed granular deposits of IgG, C3, and fibrinogen along the glomerular basement membrane and mesangial matrix. The pathogenesis of RPGN in this case may relate to the deposition of immune complexes in the glomeruli because immunofluorescent examination was revealed to be the immune-complex type, but not pauci immune type nephritis. Liver histology revealed chronic active hepatitis with mild piecemeal necrosis and did not reveal vasculitis. Although her renal function was improved after treatment with prednisolone, she suffered from pulmonary manifestations(dry cough etc.) on the 120th hospital day. Suddenly she died because of pulmonary hemorrhage on the 180th hospital day. These findings suggest that various HCV-induced immunological abnormalities, such as positive MPO-ANCA, cryoglobulinemia and hypocomplementemia, play an important role in the pathogenesis of this RPGN, although we could not demonstrate deposition within glomeruli of immune complexes containing HCV. The effect of interferon therapy on such immunological abnormalities remains to be documented. Since interferon is known to have immunomodulatory effects, we selected corticosteroid therapy. Future studies need to focus on the optimal treatment strategy for hepatitis C virus-associated glomerulonephritis.
 ...
PMID:[A case of hepatitis C virus-associated glomerulonephropathy presenting with MPO-ANCA-positive rapidly progressive glomerulonephritis]. 1089 95

Antineutrophil cytoplasmic autoantibodies (ANCA) are commonly associated with a necrotizing and crescentic glomerulonephritis (GN) that is pauci-immune, with few or no glomerular immune complex deposits detectable by immunofluorescence (IF) or electron microscopy (EM). Immunoglobulin A (IgA) nephropathy may also be manifest as a crescentic GN, but it is characterized by mesangial immune complex deposits containing IgA and is rarely associated with myeloperoxidase (MPO)- or proteinase 3 (PR3)-specific ANCA when an enzyme immunoassay is used to detect these antibodies. This report describes six patients with severe crescentic GN with mesangial IgA deposits by IF and mesangial electron-dense deposits by EM in patients with positive ANCA serological test results (four patients, anti-PR3; one patient, anti-MPO; one patient, anti-PR3 and anti-MPO). Patients presented with acute or progressive renal insufficiency, hematuria, proteinuria (nephrotic range in two patients), and hypertension. Three patients had evidence of systemic vasculitis: two patients at initial presentation and one patient later in the clinical course. Renal biopsy specimens showed crescents in greater than 50% of glomeruli in all cases, but only mild, focal and segmental mesangial and endocapillary hypercellularity, more typical of ANCA-associated crescentic GN than of crescentic IgA nephropathy without associated ANCA. Semiquantitative analysis of mesangial and endocapillary cellularity performed on renal biopsy slides from these six patients and from eight ANCA-negative patients with IgA nephropathy and crescents in greater than 50% of glomeruli showed significantly greater hypercellularity in the ANCA-negative cases. Three of five ANCA-positive patients for whom follow-up clinical data were available showed improved renal function after treatment with cyclophosphamide and corticosteroids and have not developed end-stage renal disease 17, 20, and 25 months postbiopsy. The remaining two patients were dialysis dependent at the time of biopsy and have remained so despite treatment with cyclophosphamide and corticosteroids. The findings suggest an overlap syndrome of ANCA-associated crescentic GN and IgA nephropathy that resembles the former both histologically and in its potential to respond to aggressive therapy if detected relatively early in its course.
 ...
PMID:ANCA-associated crescentic glomerulonephritis with mesangial IgA deposits. 1100 72

Sclerodema renal crisis is the usual form of presentation of renal disease in systemic sclerosis. We report a woman who at age 63 was given a diagnosis of scleroderma with Raynaud's phenomenon and cutaneous, oesophageal and lung involvement but no evidence of renal disease and no treatment with D-penicillamine. Two years later she developed progressive renal failure, nephrotic range proteinuria, haematuria and the presence of serum MPO-ANCA; she was normotensive. Renal biopsy revealed extracapillary and necrotizing glomerulonephritis and skin biopsy showed leucocytoclastic vasculitis. This clinical picture was compatible with necrotizing vasculitis of the microscopic polyarterits type. After treatment with pulse steroids followed by oral steroids and monthly intravenous cyclophosphamide her renal function stabilised and the serum MPO-ANCA disappeared.
 ...
PMID:[Progressive systemic sclerosis associated with anti-myeloperoxidase ANCA vasculitis with renal and cutaneous involvement]. 1103 66

Nephrolithiasis (kidney stones) affects 5-10% of adults and is most commonly associated with hypercalciuria, which may be due to monogenic renal tubular disorders. One such hypercalciuric disorder is Dent's disease, which is characterized by renal proximal tubular defects that include low molecular weight proteinuria, aminoaciduria and glycosuria, together with rickets in some patients. Dent's disease is due to inactivating mutations of the renal-specific voltage-gated chloride channel, CLC-5, which is expressed in the proximal tubule, thick ascending limb and collecting duct. The subcellular localization of CLC-5 to the proximal tubular endosomes has suggested a role in endocytosis, and to facilitate in vivo investigations of CLC-5 in Dent's disease we generated mice lacking CLC-5 by targeted gene disruption. CLC-5-deficient mice developed renal tubular defects which included low molecular weight (<70 kDa) proteinuria, generalized aminoaciduria that was more pronounced for neutral and polar amino acids, and glycosuria. They also developed hypercalciuria and renal calcium deposits and some had deformities of the spine. Furthermore, endocytosis as assessed by horseradish peroxidase uptake in the proximal tubule was severely impaired in CLC-5-deficient mice, thereby demonstrating a role for CLC-5 in endosomal uptake of low molecular weight proteins. Thus, CLC-5-deficient mice provide a model for Dent's disease and this will help in elucidating the function of this chloride channel in endocytosis and renal calcium homeostasis.
 ...
PMID:Mice lacking renal chloride channel, CLC-5, are a model for Dent's disease, a nephrolithiasis disorder associated with defective receptor-mediated endocytosis. 1111 37

We present 3 cases of anti-myeloperoxidase, anti-neutrophil cytoplasmic antibody (MPO-ANCA)-positive rapidly progressive glomerulonephritis developed during the treatment with D-penicillamine (D-PC) for rheumatoid arthritis. Rheumatoid arthritis was diagnosed in these patients, and D-PC was administered to them at doses of 100, 200, and 300 mg per day for 32, 42, and 39 months, respectively. They developed proteinuria, hematuria, renal insufficiency, and anemia, and D-PC was stopped. On admission, MPO-ANCA was strongly positive in their sera. Renal biopsy showed glomerulonephritis with cellular crescents. Immunofluorescence examination revealed deposits of granular IgG, IgM, IgA, C1q, and C3 in the mesangium. The 3 patients were treated with steroid pulse therapy along with administration of anticoagulants, and cyclophosphamide was also used in 2 patients. Their renal function improved gradually and MPO-ANCA disappeared after immunosuppressive treatment.
 ...
PMID:Rapidly progressive glomerulonephritis with D-penicillamine. 1114 53

The main target organs of myeloperoxidase (MPO) antineutrophil cytoplasmic antibodies (ANCA)-related disease are the kidney and lung. This report describes a 71-year-old man with rapidly progressive glomerulonephritis (RPGN) and interstitial pneumonitis associated with MPO ANCA. The patient was admitted to our hospital because of bloody sputum, low grade fever and appetite loss on October, 1998. He was diagnosed as having interstitial pneumonitis from the findings of chest X-ray and CT examinations. Moderate proteinuria and hematuria, renal dysfunction(serum creatinine: 5.6 mg/dl, BUN: 58.0 mg/dl) and positivity for MPO ANCA were noted. He was negative for anti-glomerular antibody and PR3-ANCA. Renal biopsy was performed and revealed crescentic glomerulonephritis without deposition of immunoglobulins. Therefore, the diagnosis of pauci immune type RPGN was made. Pulse therapy with methylprednisolone(1.0 g/day x 3 days) following oral administration of prednisolone (60 mg/day) found marked improvement of renal function maintenance and interstitial pneumonitis, respectively. However, he died because of lung tuberculosis and acute tuberculous pericarditis during treatment with prednisolone. In this case, MPO ANCA might have been directly associated with both RPGN and interstitial pneumonitis. Furthermore, chronic lung disease, such as interstitial pneumonitis, is important as a preceding disease of RPGN. MPO ANCA-related disease is more frequent in aged persons, therefore particular attention should be paid during their treatment with an immunosuppressant.
 ...
PMID:[A case of MPO ANCA associated glomerulonephritis with interstitial pneumonitis complicated with lung tuberculosis and pericarditis]. 1115 3

We report here 4 patients with Churg-Strauss syndrome (CSS) who had classic symptoms including a history of bronchial asthma, severe eosinophilia and necrotizing vasculitis. The antineutrophil antibody (ANCA) against myeloperoxidase (MPO) titers was elevated (44-877 ELISA units), but the ANCA against proteinase-3 (PR3) was negative in all patients. One case was complicated with systemic inflammatory response syndrome (SIRS) and required plasmapheresis and continuous hemodiafiltration. One other patient clinically showed rapidly progressive glomerulonephritis and had hemodialysis 24 times. Two of 4 patients showed good responses with corticosteroid therapy alone, while 2 patients required the addition of cyclophosphamide. Urinary abnormalities such as proteinuria or microscopic hematuria were found in all patients. Three patients had a decreased glomerular filtration rate (GFR) and renal biopsy specimens obtained from these patients showed crescentic glomerulonephritis. One patient had mild to moderate mesangial-proliferative glomerulonephritis with interstitial eosinophilic infiltration. These findings suggest that renal involvements in CSS may not be as uncommon a disorder as previously considered, especially when MPO-ANCA is positive. MPO-ANCA may be associated with the onset of glomerular disorders in CSS.
 ...
PMID:Glomerular lesions in patients with Churg-Strauss syndrome and the anti-myeloperoxidase antibody. 1143 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>