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)

Myofibroblasts play an important role in wound healing in a variety of tissue injuries. They have also been implicated in tissue fibrosis including renal scarring. This study was aimed at defining their role in one of the commonest forms of nephrotic syndrome in adults, namely membranous nephropathy. We have studied 21 patients with biopsy proven idiopathic membranous nephropathy who were treated with glucocorticoids, attempting to define the role of myofibroblasts (alpha-smooth muscle actin-positive as well as vimentin-positive cells) in the progression of this form of nephropathy. There were 13 non-progressors (NP) and 8 progressors (P). The clinical, histological, and immunohistochemical characteristics of both groups were compared. Immunohistochemical staining for myofibroblasts cytoplasmic markers a-smooth muscle actin (alpha-SMA) and vimentin relied on an avidin-biotin-peroxidase method. The level of blood pressure, degree of proteinuria, severity of interstitial infiltrate and interstitial fibrosis did not differentiate P from NP. However, vascular sclerosis was more severe in P compared to NP (p < 0.016) and its severity predicted the subsequent functional outcome (slope of the 1/serum creatinine against time; r2 = 0.618, p < 0.01). Mesangial alpha-SMA was significantly higher in P (31 +/- 18.6%) than in NP (14.5 +/- 9.8%), p < 0.015. Interstitial alpha-SMA immunostain was also higher in P but did not reach statistical significance. However, the number of interstitial myofibroblasts (alpha-SMA positive cells) closely predicted the subsequent rate of the progression of chronic renal failure (r2 = 0.919, p < 0.0001). Mesangial vimentin expression was not different between both groups. By contrast, interstitial vimentin immunostain was higher in P (19.1 +/- 8.8%) compared to NP (7.9+/-5.6 %), p < 0.002. These data suggest that the expression of mesangial and interstitial cytoskeletal proteins (alpha-SMA and vimentin) may have useful prognostic implications as they appear to differentiate between patients with membranous nephropathy who respond to immunosuppression and those who continue to progress.
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PMID:Expression of cytoskeletal proteins differentiates between progressors and non-progressors in treated idiopathic membranous nephropathy. 963 37

Transplantation of MHC-compatible, T-cell-depleted, bone marrow cells has successfully treated autoimmunities, immunodeficiencies, malignancies, and developmental deficiencies of the hematopoietic system. Recombinant inbred SCG/Kj mice develop spontaneous crescentic glomerulonephritis, systemic vasculitis, and a lymphoproliferative disorder early in life. To determine whether the precipitous autoimmune disease of SCG/Kj mice could be treated by bone marrow transplantation, 30 SCG/Kj mice were engrafted with T-cell-depleted, bone marrow (TCDM) from allogeneic, MHC-compatible, autoimmune-resistant C3H/He donors, and 30 SCG/Kj mice served as controls and received TCDM from syngeneic, SCG/Kj donors. A significant survival advantage was evident from SCG/Kj mice engrafted with C3H/He TCDM (p < 0.005), and an 89% extension of median survival compared to recipients of SCG/Kj TCDM. Within 28 weeks post-transplantation, 62% of mice engrafted with SCG/Kj TCDM had died with clinical signs of fatal crescentic glomerulonephritis. This result compared with only 10% of mice engrafted with C3H/He TCDM. Mice engrafted with SCG/Kj TCDM developed significantly greater titers of autoantibodies to ss-DNA, ds-DNA, and myeloperoxidase (ANCA) (p < 0.001), had shorter latencies to the development of, and a greater incidence of proteinuria, hematuria, and peripheral lymphadenopathy, and a greater mean grade of glomerular lesion (p < 0.001), than mice engrafted with C3H/He TCDM. These findings indicate that the genetic defect of the SCG/Kj strain of mice resides within the hematopoietic stem cells and provokes the speculation that bone marrow transplantation might be a useful means of treating progressive crescentic glomerulonephritis in humans.
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PMID:Prevention of crescentic glomerulonephritis in SCG/Kj mice by bone marrow transplantation. 964 40

Patients with anti-myeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN) may develop chronic renal failure (CRF) leading to end-stage renal disease despite an initially favorable response to treatment. The aim of this study was to determine the prognostic value of clinical, laboratory, and histopathologic features at the time of presentation and during follow-up for the development of CRF in 21 consecutive anti-MPO-positive patients with NCGN. Renal function did not recover in two of five patients who were dialysis-dependent at presentation. The remaining 19 patients all went into remission and were off dialysis at 3 mo after diagnosis. At long-term follow-up, nine of these patients had stable renal function and did not relapse (group A), five patients developed CRF without signs of relapse (group B), and five patients relapsed (group C). At diagnosis, serum creatinine, C-reactive protein, and anti-MPO levels did not differ between groups A, B, and C. Microscopic erythrocyturia resolved in all patients within 4 mo of treatment. BP at presentation and during follow-up did not differ between groups A, B, and C. Proteinuria at diagnosis and in the first 6 mo after diagnosis was higher in patients who developed CRF than in patients with a stable renal function. Anti-MPO levels at 3 mo had decreased compared with anti-MPO levels at diagnosis in groups A and C, whereas anti-MPO levels did not fall significantly in patients who developed CRF. The predictive value of a renal biopsy at diagnosis on long-term renal outcome was limited. In conclusion, a higher degree of proteinuria at diagnosis and during follow-up as well as persistently elevated anti-MPO levels after induction of remission are associated with the development of CRF and are predictive of poor renal outcome in anti-MPO-associated NCGN.
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PMID:Determinants of renal outcome in anti-myeloperoxidase-associated necrotizing crescentic glomerulonephritis. 977 93

We have examined the effects of the calcium channel blocker verapamil on the renal glomerular structural damage produced by mercuric chloride in rats. Verapamil (75 micrograms/kg body wt iv) was administered 30 min prior to mercuric chloride injection (HgCl2, 5 mg/kg body wt sc). Verapamil prevented the glomerular proteinuria observed in HgCl2-treated rats. Isolated glomeruli from mercury-treated rats 1 h after injection presented a diminished cross-sectional area as compared with control glomeruli (control [micron2], 26,310 +/- 2545; HgCl2 [micron2], 18,474 +/- 1828) and increased glomerular calcium content (control, 23 +/- 6 nmol/mg protein; HgCl2, 43 +/- 7 nmol/mg protein). Verapamil pretreatment prevented glomerular cross-sectional area (GCSA) diminution and glomerular calcium content rise (GCSA [micron2] Vp + Hg, 28,281 +/- 4654, Ca2+ [nmol/mg protein] Vp + Hg, 18 +/- 5). Renal sections prepared for immunohistochemical detection and histochemical analysis showed increased deposits of fibronectin and lipids and enhanced cellularity in glomerular structures from HgCl2-treated rats. Renal sections from animals pretreated with verapamil showed fibronectin and lipid contents not different from control sections and their histological studies did not show any changes when compared with control. Verapamil pretreatment also protected glomeruli from enhanced leukocyte content (myeloperoxidase activity/mg protein): control, 59 +/- 7; HgCl2, 134 +/- 10; Vp + Hg, 79 +/- 11). HgCl2 also contracts GCSA in vitro; Vp prevented this GCSA diminution. The results described in this study indicate that mercuric chloride nephrotoxicity may be associated not only with changes in renal glomerular haemodynamics, but also with a direct effect on glomerular cells.
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PMID:Verapamil protection against mercuric chloride-induced renal glomerular injury in rats. 985 4

We treated a 13-year-old girl who developed myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-related crescentic glomerulonephritis (GN) during propylthiouracil (PTU) treatment for Graves' disease. MPO-ANCA-related crescentic GN during PTU therapy has been described previously in only one recent report of 2 children. We report this case here and describe 15 (13 adult cases) more patients with MPO-ANCA-related GN associated with PTU found in a literature review. The mean age at onset was 41.3 years, and the length of PTU administration ranged from 2 weeks to 6 years (mean 3.5 years). Clinical signs and symptoms were hematuria (100%), proteinuria (100%), arthralgia (7 of 16 cases; 43.8%), fever (4 cases; 20.0%), purpura (2 cases; 12.5%), skin ulcer (1 case; 6.3%) and dyspnea (1 case; 6.3%). These patients were treated with steroid (15 cases; 93.8%), cyclophosphamide (8 cases; 50.0%), steroid pulse therapy (4 cases; 25.0%), or plasma exchange (1 case; 6.3%), or were not treated (1 case; 6.3%). Most patients revealed crescentic GN (15 cases; 93.8%) on renal biopsy, while one exhibited mesangial proliferative GN (6.3%). For 2 of the 16 patients (12.5%) irreversible renal dysfunction persisted and hemodialysis was started. Patients with Graves' disease treated with PTU should be observed carefully by urinalysis and monitoring of the serum creatinine level.
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PMID:[A pediatric case of myeloperoxidase-antineutrophil cytoplasmic (ANCA)-related crescentic glomerulonephritis associated with propylthiouracil treatment for Graves' disease]. 989 62

Scleroderma renal crisis is characterized by intimal thickening of the afferent glomerular arterioles resulting in hypertension and fibrinoid necrosis of the capillary tuff. We report a 67-year-old man with long-standing systemic sclerosis who developed normotensive progressive renal failure, proteinuria, and a nephritic urinary sediment with serum myeloperoxidase-antineutrophil cytoplasmatic antibodies (MPO-ANCA). Renal biopsy showed pauci-immune crescentic glomerulonephritis but none of the typical vascular changes of scleroderma renal crisis. Because comparable cases have recently been reported from Japan, normotensive MPO-ANCA-positive crescentic glomerulonephritis may form an entity of progressive renal failure in scleroderma.
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PMID:MPO-ANCA-Positive crescentic glomerulonephritis: a distinct entity of scleroderma renal disease? 1019 34

In many diseases and acute inflammatory disorders, important components of pathological processes are linked to the neutrophils' ability to release a complex assortment of agents that can destroy normal cells and dissolve connective tissue. This review summarizes the mechanisms of tissue destruction by neutrophils and the role of kidney-specific factors that promote this effect. Nicotinamide adenine dinucleotide phosphate H (NADPH) oxidase is a membrane-associated enzyme that generates a family of reactive oxygen intermediates (ROI). There is increasing evidence that ROIs are implicated in glomerular pathophysiology: ROIs contribute to the development of proteinuria, alter glomerular filtration rate, and induce morphological changes in glomerular cells. Specific neutrophil granules contain microbicidal peptides, proteins, and proteolytic enzymes, which mediate the dissolution of extracellular matrix, harm cell structures or cell function, and induce acute and potentially irreparable damage. Although both ROI and neutrophil-derived proteases alone have the potential for tissue destruction, it is their synergism that circumvents the intrinsic barriers designed to protect the host. Even small amounts of ROI can generate hypochlorus acid (HOCl) in the presence of neutrophil-derived myeloperoxidase (MPO) and initiate the deactivation of antiproteases and activation of latent proteases, which lead to tissue damage if not properly controlled. In addition, neutrophil-derived phospholipase products such as leukotrienes and platelet-activating factor contribute to vascular changes in acute inflammation and amplify tissue damage. Increasing evidence suggests that mesangial cells and neutrophils release chemotactic substances (eg, interleukin 8), which further promote neutrophil migration to the kidney, activate neutrophils, and increase glomerular injury. Also, the expression of adhesion molecules (eg, intercellular adhesion molecule 1 on kidney-specific cells and beta-2-integrins on leukocytes) has been correlated with the degree of injury in various forms of glomerulonephritis or after ischemia and reperfusion. Together, these results suggest that neutrophils and adhesion molecules play an important role in mediating tissue injury with subsequent renal failure. Conversely, chronic renal failure reduces neutrophil function and thereby can increase susceptibility to infection and sepsis.
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PMID:Neutrophils and renal failure. 1043 Sep 93

In September 1997, a 68-year-old woman was found to have proteinuria and renal dysfunction. In December 1997, renal biopsy revealed necrotizing crescentic glomerulonephritis and membranous glomerulonephropathy. We diagnosed myeloperoxidase antineutrophil cytoplasmic antibody-positive necrotizing crescentic glomerulonephritis and membranous glomerulonephropathy because of the presence of necrotizing cellular crescents and spike lesions in the subepithelial region of the glomerular basement membrane. After steroid therapy, the antibody level and the incidence of cellular crescents showed a decrease. This is a rare case of myeloperoxidase antineutrophil cytoplasmic antibody-positive necrotizing crescentic glomerulonephritis associated with membranous glomerulonephropathy.
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PMID:Myeloperoxidase antineutrophil cytoplasmic antibody-positive necrotizing crescentic glomerulonephritis and membranous glomerulonephropathy. 1054 28

We present here a case of MPO-ANCA positive rapidly progressive glomerulonephritis (RPGN) after 34 months of D-penicillamine (D-PC) therapy for rheumatoid arthritis (RA). A 27-year-old Japanese woman was diagnosed as having RA in June 1994 at our out-patient clinic. Oral D-PC administration was initiated at a dose of 100 mg per day in January 1995. In August 1997, proteinuria, hematuria, renal insufficiency, and anemia developed. D-PC was withdrawn promptly, and prednisolone 5 mg per day was started. The patient was admitted to our hospital in September. On admission, anti-neutrophil cytoplasmic antibody against mycloperoxidase (MPO-ANCA) was strongly positive in the serum. Renal biopsy showed glomerulonephritis with cellular crescent formation in 60% of the glomeruli observed. Immunofluorescence examinations revealed deposits of granular IgG, IgA, C 1 q, and C 3 in the mesangium. The patient was treated with steroid pulse therapy along with administration of anti-coagulation and anti-platelet agents under the diagnosis of MPO-ANCA positive D-PC-induced RPGN. The renal function was gradually recovered and MPO-ANCA disappeared. Since RPGN is potentially a fatal disease, frequent monitoring of renal function and discontinuation of D-PC are required. In case MPO-ANCA becomes positive, prompt and correct diagnosis of the renal disorder could lead to a good prognosis as in this case. The present case may provide some important immunological insights into medical procedures to treat D-PC-induced RPGN and MPO-ANCA related glomerulonephritis.
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PMID:[MPO-ANCA positive rapidly progressive glomerulonephritis in a patient with rheumatoid arthritis during treatment with D-penicillamine]. 1061 90

A cadaveric kidney transplant recipient, with no history of a connective tissue disease, was admitted with malaise, arthralgias, diplopia, mild headache, and a painful left eye. The patient was on maintenance immunosuppression for 14 years with cyclosporine and methylprednisolone. Initial laboratory data indicated an elevated serum creatinine from baseline, 2+ proteinuria, and 50 to 100 red blood cells (RBCs)/high-power field (HPF) in the urine. Renal biopsy was consistent with necrotizing vasculitis involving glomerular capillaries, with crescent formation and an absence of immune complexes. Perinuclear antineutrophil cytoplasmic autoantibodies (P-ANCA) and anti-myeloperoxidase (MPO) were found to be elevated. To the best of our knowledge, this is the first reported case of an ANCA-associated small vessel vasculitis (SVV) developing in a renal transplant recipient without history of connective tissue disease.
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PMID:De novo ANCA-associated vasculitis occurring 14 years after kidney transplantation. 1069 95


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