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)

Diabetic nephropathy is characterized by albuminuria which proceeds to overt proteinuria. The highly negatively stained HS side chain of heparan sulphate proteoglycan (HSPG) is a major determinant of the charge-dependent permeability of the GBM. We set out to study the presence of HS and HSPG in the GBM of patients with diabetic nephropathy using newly developed monoclonal antibodies, and to compare HSPG expression to the expression of other previously investigated glomerular extracellular matrix compounds. Immunohistochemically, glomerular extracellular matrix components were analysed in 14 renal biopsies of patients with diabetic nephropathy and compared with those of normal control subjects. Monoclonal antibodies used were: JM403 against the HS side chain of GBM HSPG and JM72 against the HSPG-core protein. Also, a polyclonal antiserum (B31) against human GBM-HSPG-core protein was used. Additionally, antibodies were used against collagen types I, III, IV and against alpha 1 (IV)NC, alpha 3(IV)NC and fibronectin. Staining was scored for intensity and for staining pattern by four independent observers who had no previous knowledge of the sample origin. No glomerular staining was seen for collagen type I. Collagen type III was present in some diabetic nodules. Anti-collagen type IV showed a decreased GBM staining in patients with diabetic nephropathy (p = 0.04). With anti-alpha 1 (IV)NC no changes in GBM staining intensity were observed; with anti-alpha 3 (IV)NC brilliant GBM staining was seen in both groups. Increased mesangial staining (p = 0.003) was seen with anti-collagen type IV in biopsies with nodular lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of glomerular extracellular matrix components in human diabetic nephropathy: decrease of heparan sulphate in the glomerular basement membrane. 748 52

Fibrin is an important mediator of injury in severe proliferative forms of glomerulonephritis (GN). Normal glomeruli express fibrinolytic activity, which may protect against the injurious effects of fibrin deposition. Changes in glomerular fibrinolytic activity (GFA) may play an important role in modulating fibrin accumulation in GN. To study the changes in GFA associated with fibrin deposition in GN, autologous phase anti-glomerular basement antibody initiated GN (anti-GBM GN) was studied in rabbits. Net GFA was significantly reduced in association with glomerular fibrin deposition (1.3 +/- 0.8 ng fibrin lysed/10(3) glomeruli/2 hr, normal 57.1 +/- 25.4 ng fibrin lysed/10(3) glomeruli/2 hr, P < 0.02). Reduced GFA in fibrin associated GN was associated with decreased expression of tissue type plasminogen activator (tPA) and increased expression of plasminogen activator inhibitor type-1 (PAI-1) and glomerular macrophage infiltration. In a fibrin independent model of anti-GBM induced GN (heterologous phase), with equivalent injury (proteinuria), net GFA was increased (174 +/- 64 ng fibrin lysed/10(3) glomeruli/2 hr). This was associated with increased tPA and uPA, and decreased PAI-1 in the absence of significant macrophage infiltration. These studies demonstrate that fibrin deposition in GN is associated with a net reduction of GFA, attributable to reduced expression of plasminogen activators and augmentation of PAI-1. Reduction of GFA may potentiate glomerular fibrin deposition and consequent glomerular injury. The association between glomerular macrophage influx and reduction in GFA suggests that this change may be directed by macrophages.
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PMID:Glomerular fibrinolytic activity in anti-GBM glomerulonephritis in rabbits. 823 Oct 28

According to its immunopharmacological profile, 15-deoxyspergualin (15-DOS) has been investigated as to its disease-modifying activity on HgCl2-induced glomerulonephritis (GN) and on tubulointerstitial nephritis (TIN) in Brown-Norway rats. Both models are induced autoimmune disorders in which afflicted animals display high levels of serum autoantibodies directed against the glomerular or tubular basement membrane (GBM or TBM), respectively. The diseases are manifested by high serum creatinine and urea levels with severe proteinuria. In the model of HgCl2-GN, administration of 15-DOS clearly led to a reduction of proteinuria and decreased the amount of rat IgG attached to the GBM. Furthermore, a therapeutic effect could be demonstrated when 15-DOS was given after the appearance of clinical symptoms. Not only urine-protein values but also anti-laminin antibodies returned to normal levels. Also in the experimental TIN-model, 15-DOS, either given during the induction phase, or even late in the onset of the disease, strongly prevented the proteinuria of this autoimmune disease and inhibited the formation of autoantibodies to TBN.
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PMID:Immunosuppressive therapy of organ-specific nephritic autoimmune diseases with 15-deoxyspergualin. 827 49

The requirements for a diagnosis of Goodpasture's syndrome (GPS) include: (1) the presence of glomerulonephritis, (2) alveolar bleeding, and (3) the presence of anti-glomerular basement membrane (anti-GBM antibody). Among Japanese case, the 2 patients reported here were rare in that they satisfied all of these requirements. In case 1 (a 40-year-old male), the disease developed with initial signs of proteinuria and hematuria. The patient developed hemoptysis after hospitalization. The interval from onset to hospitalization was 38 days. The serum creatinine (CRN) level was 3.6 mg/dl on admission. The pathological findings were rated as full-circumferential, cellular crescentic nephritis, and the patient did not display oliguria. The renal and pulmonary impairments in this case were markedly improved by glucocorticoid (prednisolone PSL, 60 mg/day), cyclophosphamide therapy (50 mg/day) and plasma exchange (PE 10 times). In case 2 (a 58-year-old male), the initial signs developed as proteinuria and hematuria, followed by rapidly progressive renal functional deterioration and hemoptysis occurred. Compared to Case 1, the interval from onset to hospitalization was longer in Case 2 (125 days) and the CRN level was also higher (10.7 mg/dl). Case 2 was rated as full-circumferential, fibrous crescentic nephritis, and the patient was oliguric. Although the pulmonary impairment was reduced by pulse therapy and 10 PEs, recovery of renal function has not been achieved, still necessitating maintenance hemodialysis at present. In case 1, the disease relapsed at 4.5 years after remission, presenting with aggravated renal function and hemoptysis. In this case, low-dose PSL therapy had been discontinued at 3 months before the relapse.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Two cases of Goodpasture's syndrome--clinicopathological studies and relapse. 833 6

During the period from January 1973 to December 1970, 774 renal transplantations in 698 children have been performed in our Renal Unit. A total of 540 grafts have been examined both by light and immunofluorescence microscopy at least once. Recurrent glomerulonephritis was diagnosed in 62 grafts, de novo glomerulonephritis in 68 and allograft glomerulopathy (AGP) in 38. AGP was defined as a lesion affecting all glomeruli and characterized by widespread reduplication of the GBM with widening of the subendothelial space and interposition of mesangial matrix and without significant deposits by immunofluorescence. The aim of the current study is to describe the natural history of AGP and to delinate its clinical significance. At time of biopsy, an increase in serum creatinine was present in 30 patients associated with a proteinuria > or = 1 g/day in 21. During the post-transplantation course, proteinuria was present in 29 patients and associated with a nephrotic syndrome in 10 of them. With a mean follow-up of eight years seven months, two patients died, 23 lost their grafts and 13 have a functioning graft. The lesions of AGP recurred in three of the nine children who received a second graft. Thirteen of the 33 patients in whom earlier biopsies were performed showed a different pattern of involvement characterized by a prominent swelling of active endothelial and mesangial cells and a hypercellularity related to the presence of mononuclear cells both in the lumens and in the mesangial areas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A specific glomerular lesion of the graft: allograft glomerulopathy. 836 Nov 20

In Brown-Norway rats HgCl2 induces an autoimmune disease due to a T-dependent B cell polyclonal activation. This disease is marked by the production of numerous antibodies including antiglomerular basement membrane (GBM) antibodies. Rats exhibit a biphasic glomerulopathy with heavy proteinuria. Initially anti-GBM antibodies are found linearly deposited; they precede the appearance of membranous glomerulopathy. Rats recover spontaneously even if HgCl2 injections are pursued, but mechanisms at play are unclear. We have assessed the effects of transplanting the spleen from a BN rat, either at the acme of the disease or at the time of convalescence, into naive BN rats, some of which were then injected with HgCl2. Transplantation of a spleen from HgCl2-injected rats at the acme of the disease dramatically protects BN rats from all the manifestations of the mercury disease. BN rats transplanted with a spleen from HgCl2-injected rats at the time of convalescence only exhibited a typical membranous glomerulopathy with heavy proteinuria but without circulating anti-GBM antibodies. Antilaminin antibodies were eluted from the glomeruli. This study shows that spleen cells from HgCl2-injected rats are able to confer tolerance to HgCl2-induced autoimmunity. It also shows that some B cell clones escape this tolerance. Finally, this study strongly suggests that membranous glomerulopathy, responsible for proteinuria in this model, is related to the presence of antilaminin antibodies.
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PMID:Evidence for a role of antilaminin-producing B cell clones that escape tolerance in the pathogenesis of HgCl2-induced membranous glomerulopathy. 838 32

Sixty-three patients, (52 males and 11 females) from 28 kindreds of hereditary nephritis (Alport's syndrome) were identified over a 14-year period from 1977 to 1991. Group I included 51 patients with (a) positive family history of haematuria with or without chronic renal failure, (b) characteristic GBM changes on electron-microscopy, (c) characteristic ocular signs, and (d) high-frequency sensorineural deafness. Group II included 12 patients with a negative family history. All of them had evidence of renal disease with characteristic ocular signs and deafness and four had characteristic GBM changes on electron-microscopy. The main clinical features were haematuria in 96.8%, deafness in 82.5%, and diminished visual acuity in 66.7% of affected subjects. Hypertension was present in 71.4% patients. Pure tone audiometry revealed high-frequency sensorineural deafness in 96.8%. Ocular examination showed bilateral anterior lenticonus in 37.8%, retinal flecks in 22.2%, cataract in 20%, and keratoconus in 6.7% patients. Proteinuria (> 2.0 g/24 h) was detected in 31.8%. Sixteen (57.1%) of the 28 index patients (all males) were diagnosed for the first time when they presented with end-stage renal disease. Serum creatinine in the overall group ranged from 0.9 to 18.7 mg/dl(7.81 +/- 5.37 mg/dl). Adequate renal tissue was obtained by biopsy in 14 patients. Light-microscopy revealed focal segmental glomerulosclerosis in five, mesangial proliferation in four, chronic interstitial nephritis in three, and mesangiocapillary and crescentic glomerulonephritis in one each. Electron-microscopy showed characteristic changes in the GBM in seven specimens.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hereditary nephritis (Alport's syndrome)--clinical profile and inheritance in 28 kindreds. 841 53

The role of interleukin-1 (IL-1) in the pathogenesis of experimental crescentic glomerulonephritis was investigated. Administration of the interleukin-1 receptor antagonist (IL-1ra) was used to block the action of IL-1 during disease development. Two groups of six rats were primed with rabbit IgG, followed five days later by injection of rabbit anti-GBM serum (day 0). Animals were treated with a constant infusion of recombinant human IL-1ra (plasma level approximately 100 to 200 ng/ml) or saline (untreated) from day -1 until being killed on day 14. Untreated animals exhibited severe proteinuria and development renal dysfunction shown by increased serum urea and serum creatinine and reduced creatinine clearance. In contrast, IL-1ra treated animals had significantly reduced proteinuria (IL-1ra vs. untreated, P < 0.05) and maintained normal renal function (IL-1ra vs. untreated, P < 0.05). Histologically, IL-1ra treatment markedly reduced glomerular hypercellularity, glomerular necrosis and crescent formation and almost completely abrogated tubular atrophy and fibrosis. IL-1ra treatment suppressed glomerular macrophage accumulation by 57% (P < 0.01), while macrophage accumulation in the interstitium was completely abrogated and immune activation of the interstitial T cell infiltrate was prevented. This study demonstrates that IL-1 plays a key role in the pathogenesis of anti-GBM glomerulonephritis, and blocking its effects may provide a novel therapeutic approach to the treatment of human progressive glomerulonephritis.
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PMID:Suppression of experimental crescentic glomerulonephritis by the interleukin-1 receptor antagonist. 844 Dec 45

There is considerable disagreement regarding the natural history of renal disease associated with thin glomerular basement membranes (TGBM). We followed 43 patients (19 male), mean age 41.6 years (range 19-73) for a mean of 88 months (48-140). TGBM was recognized in adults when glomerular basement membrane thickness, measured from multiple sites in electronmicrographs of renal biopsy tissue as the harmonic mean, was < 320 nm. At presentation, 95% had microscopic haematuria, 12% macroscopic haematuria, 14% loin pain, 28% proteinuria, and 14% hypertension. There was no difference in GBM width between the sexes (male 258 nm vs. female 251 nm) but there was a significant negative correlation between age and GBM width (r = -0.53, p < 0.001), with older patients having the thinnest membranes. Twenty six patients had ultrathin GBM (< 270 nm), of whom 54% had 3+ haematuria vs. 12% of the group with BM > 270 nm (p < 0.01). In the ultrathin group, 71% had loss of anionic charge from the GBM, vs. 17% in those with membranes which were thin but > 270 nm (p < 0.05). Proteinuria occurred more frequently in those with GBM > 270 nm, 65% vs. 8% in the ultrathin group (p < 0.01). Thin GBM were associated with a benign prognosis, as after a mean follow-up of 85 months (48-140), there was no significant change in either serum creatinine or mean arterial blood pressure. Patients with ultrathin GBM had greater loss of GBM anionic charge, which might result in both an alteration of flow characteristics within the glomerular capillaries and also increased fragility of the glomerular basement membrane with likelihood of rupture and resultant macroscopic haematuria.
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PMID:Clinical features and outcome of patients with thin and ultrathin glomerular membranes. 854 63

In the kidneys of anti-glomerular basement membrane (anti-GBM) antibody disease, binding of antibodies to tubular basement membrane (TBM) is often observed. The present work was performed to explore the mechanisms of binding of anti-GBM antibodies to TBM in vivo with special reference to 5I2Ag, a rat membrane inhibitor of complement which regulates complement activation at C3 convertase level. To suppress functions of renal 5I2Ag, F(ab')2 fragment of 5I2 (a neutralizing mAb against 5I2Ag) was perfused in the left kidney and then blood circulation was restored. Mild proteinuria ( < 10 mg/16 hr) was observed during first several days. Five days later, there were tubulointerstitial injuries defined by tubular vimentin staining and leukocyte infiltration. Significant deposition of C3 was observed in the capillaries and in TBM. In rats intravenously injected with rabbit anti-rat GBM antibodies five minutes after kidney perfusion with 5I2, strong binding of rabbit IgG to TBM was observed at one and five days after injection. Although these rats showed mild proteinuria comparable to those perfused with 5I2 and those injected with normal rabbit serum, tubulointerstitial injury was significantly enhanced at Day 5. In contrast, rats perfused with irrelevant mAb and injected with anti-GBM antibodies did not show any significant binding of antibodies to TBM nor tubulointerstitial injury. Furthermore, rats which were made proteinuric by puromycin aminonucleoside and injected with anti-GBM antibodies did not show any significant binding of rabbit IgG to TBM. These results indicate that 5I2Ag, a rat membrane inhibitor of complement at the C3 convertase level, regulates vascular permeability in the living kidney, and that dysfunction or decreased expression of this molecule leads to increased accessibility of anti-GBM antibodies to TBM.
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PMID:Role of a rat membrane inhibitor of complement in anti-basement membrane antibody-induced renal injury. 858 33


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