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 31-year-old man was admitted for investigation of proteinuria and hematuria. Physical examination on admission revealed systemic lymphoadenopathy, no hepatosplenomegaly, and ankle edema. Hemoglobin was 14.3 g/dl, platelet 21.4 x 10(4)/microliters and WBC 40,800/microliters which contained 86% mature lymphoid cells. Immunological phenotyping of peripheral lymphoid cells gave positive reactions for CD19, and CD20, and negative reaction for smlg. Urinary protein excretion was 8.3 g/dl in 24h. Serum total protein was 4.1 g/dl with albumin of 2.5 g/dl. Serum IgG was 302 mg/dl, IgA 43 mg/dl, and IgM 56 mg/dl. Renal biopsy showed characteristic features of membranoproliferative glomerulonephritis (MPGN). He was diagnosed as having nephrotic syndrome associated with B-cell chronic lymphocytic leukemia (B-CLL), and was treated with prednisolone and cyclophosphamide without effect. Therefore, he was treated with 18 MU of recombinant-alpha-2a-interferon (IFN-alpha)/day. This treatment resulted in almost normal WBC and differential counts, and urinary protein excretion of 3g in 24h 2 months later. After IFN-alpha treatment was discontinued, WBC count and the amount of urinary protein again increased. He was again treated with IFN-alpha at the dose of 9.0 MU/day three times a week, and is now well without any complaints. This is the first case report in which IFN-alpha was effective in a patient with nephrotic syndrome associated with B-CLL. We think that IFN-alpha therapy is worth trying in similar cases.
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PMID:[Nephrotic syndrome associated with B-cell chronic lymphocytic leukemia successfully treated with interferon-alpha]. 207 29

Allotransplantation of solid organs transfers passenger leucocytes which may give rise to a state of persistent microchimaerism. In this report we describe the case of a patient who developed a solitary plasmacytoma in a transplanted kidney more than 10 years after allografting. The diagnosis was established on the basis of the presence of a monoclonal IgG kappa peak in the serum, and light chain proteinuria, the plasmacytoid features of tumour cells including cell surface expression of IgG, kappa light chains, CD20, CD38 and CD56, the absence of lytic bone lesions and a normal bone marrow biopsy, and the disappearance of the monoclonal IgG peak after graft nephrectomy. A donor origin of the tumour was established by HLA DNA typing of tumour, tumour-free kidney tissue, and peripheral blood leucocytes, respectively.
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PMID:A solitary plasmacytoma of donor origin arising 14 years after kidney allotransplantation. 757 26

We report on a series of 26 patients diagnosed with primary (de novo) plasma cell (PC) leukemia (PCL) in whom we analyzed the clinicobiologic characteristics of the disease together with the immunophenotype, DNA cell content, proliferative index, and numeric chromosomal aberrations of the neoplastic PC, and compared them with 664 multiple myeloma (MM) patients at diagnosis. The median age, sex ratio, and bone lesion extension were similar, but PCL cases displayed a higher prevalence of clinical stage III, extramedullary involvement, and Bence Jones cases, with fewer IgA cases than for MM patients. In addition, according to several prognostic indicators (beta2-microglobulin serum level, proportion of S-phase PCs, proteinuria, calcium serum level, lactate dehydrogenase [LDH] and renal function), the incidence of adverse prognostic factors was significantly higher in PCL versus MM. Immunophenotypic expression was similar for CD38, CD138, CD2, CD3, CD16, CD10, CD13, and CD15, but PCL differed from MM in the expression of CD56, CD9 HLA-DR, CD117, and CD20 antigens. Twenty-two PCL cases were diploid and one was hypodiploid, while most MM cases (57%) showed DNA hyperdiploidy. With the fluorescent in situ hydridization (FISH) technique, 12 of 13 PCL cases displayed the numeric aberrations, -13 (86%), +/-1 (57%), +18 (43%), and -X in women (25%), but they lacked several numeric aberrations usually found in MM such as +3, +6, +9, +11, and +15. PCL cases had a lower overall response to therapy than MM cases (38% v 63%, P =.01332). Among PCL patients, a trend for a worse response was observed in cases treated with melphalan and prednisone (MP) versus polychemotherapy. Overall survival was significantly worse in PCL versus MM patients (8 v 36 months, P <.0001), but it was significantly better in PCL patients treated with polychemotherapy versus MP (18 v 3 months, P =.0137). By contrast, MM patients did not show significant differences in overall survival according to the treatment used, MP or polychemotherapy. Ten variables seemed to predict survival in PCL patients, but only the beta2-microglobulin level and S-phase PCs retained an independent value in multivariate analysis. In summary, our study illustrates that PCs from PCL display singular phenotypic, DNA cell content, and cytogenetic characteristics that lead to a different disease evolution versus MM.
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PMID:Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics. 1061 Jan 15

Currently available monoclonal antibodies against the B cell surface antigen CD20 have been employed to explore whether specific inhibition of B cells may help improve the outcome of idiopathic membranous nephropathy (IMN) and may avoid the side effects of steroids and immunosuppressants. This prospective, observational study evaluated the 1-yr outcome of eight IMN patients with persistent (>6 mo) urinary protein excretion > 3.5 g/24 h given four weekly infusions of the anti-CD20 antibody rituximab (375 mg/m(2)). At 3 and 12 mo, proteinuria significantly decreased from mean (+/- SD) 8.6 +/- 4.2 to 4.3 +/- 3.3 (-51%, P < 0.005) and 3.0 +/- 2.5 (-66%, P < 0.005) g/24 h, albumin fractional clearance from 2.3 +/- 2.1 to 1.2 +/- 1.7 (-47%, P < 0.05) and 0.5 +/- 0.6 (-76%, P < 0.003), and serum albumin concentration increased from 2.7 +/- 0.5 to 3.1 +/- 0.3 (+21%, P < 0.05) and 3.5 +/- 0.4 (+41%, P < 0.05) mg/dl. At 12 mo, proteinuria decreased to < or =0.5 g/24 h or < or =3.5 g/24 h in two and three patients, respectively. Proteinuria decreased in the remaining patients by 74%, 44%, and 41%, respectively. Body weight, diastolic BP, and serum cholesterol progressively decreased in parallel with an improvement of edema in all patients. Renal function stabilized (Delta1/creatinine: +0.002 +/- 0.007). CD20 B lymphocytes fell below normal ranges up to study-end. No patient had major drug-related events or major changes in other laboratory parameters. Rituximab thus promotes sustained disease remission in patients otherwise predicted to progress to ESRD, and it is safe. The long-term risk/benefit profile of this novel, disease-specific approach seems much more favorable to that of commonly employed immunosuppressive drugs.
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PMID:Rituximab in idiopathic membranous nephropathy: a one-year prospective study. 1281 45

Three patients (one with idiopathic thrombocytopenic purpura [ITP] and two with thrombotic thrombocytopenic purpura [TTP]) were treated with rituximab (anti-CD20 chimeric antibody) at a dose of 325 mg/m2 administered weekly after they failed standard therapies. The patient with ITP who did not respond to steroids and anti-D antibody administration achieved augmentation of her platelet counts up to 180 x 10(3)/microL after four doses of rituximab. Six months later, when her counts started to decrease, she received maintenance therapy with an additional course of 4 standard doses of antibody that resulted in consolidation of her platelet counts around 100 x 10(3)/microL. One patient with TTP and concurrent idiopathic nephropathy who was previously treated with plasmapheresis, steroids, and vincristine improved only after 4 weekly administrations of the antibody. Moreover, his nephrotic-range proteinuria resolved after he received rituximab. The other patient with chronic TTP who still relapsed after splenectomy received 5 doses of rituximab with concomitant plasmapheresis. His thrombocytopenia improved slowly, and his platelet count stabilized at 300 x 10(3)/microL. All three patients showed evidence of response to anti-CD20 antibody with improvement in clinical outcome as well as augmentation of platelet counts to normal levels. We conclude that rituximab is a useful immunomodulating adjunct in the treatment of refractory ITP and TTP.
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PMID:Rituximab for the treatment of refractory idiopathic thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura (TTP): report of three cases. 1560 92

Rituximab, a chimeric monoclonal antibody specific for human CD20, has recently been used for the treatment of autoimmune diseases. A 14-year-old patient with severe systemic lupus erythematosus (SLE) and class IV glomerulonephritis presented with immunologic and clinical resistance to conventional immunosuppressive therapy for 10 months after diagnosis. To induce remission of active SLE, treatment with 6 monthly rituximab at 375 mg/m(2), oral mycophenolate and prednisone was initiated followed by maintenance rituximab every 3 months. The SLEDAI decreased significantly from 31 at diagnosis to 14 after nine applications of rituximab. Extrarenal symptoms of SLE improved significantly. However, after induction therapy with rituximab the patient presented a reversible intrinsic acute renal insufficiency for a period of 3 weeks. The discontinuation of the daily medication (oral prednisone and mycophenolate) by the patient herself may explain the progression of active SLE associated with the reversible acute renal failure. Under intensive immunosuppressive therapy improvement of active disease manifestations and stabilization of plasma creatinine concentrations to normal values was observed. However, proteinuria remained elevated and improved only after a protracted period (median protein-to-creatinine ratio 5.2 g/g, range 0.8-11.2 g/g). Hematuria and urinary cell casts persisted. In conclusion, the extrarenal symptoms of the patient responded particularly well to rituximab. However, despite complete B-cell elimination, renal remission of SLE was not achieved. Thus, it may be possible that humoral and cellular immune mechanisms have a fundamental involvement in the pathogenesis of SLE nephritis.
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PMID:Rituximab in childhood systemic lupus erythematosus refractory to conventional immunosuppression: case report. 1650 74

Mixed cryoglobulinemia (MC) and glomerulonephritis are the most important extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. MC is a non-neoplastic B cell lymphoproliferative process induced by HCV in an antigen-driven mechanism. The clinical expression of cryoglobulinemia varies from an indolent course to the development of systemic vasculitis. Glomerulonephritis is predominantly associated with MC, and almost always takes the form of membranoproliferative glomerulonephritis. The renal manifestations may range from isolated proteinuria to overt nephritic or nephrotic syndrome with variable progression towards chronic renal insufficiency. The treatment of these virus-related diseases must be individualized on the basis of the severity of clinical symptoms. Antiviral therapy with interferon alpha and ribavirin (the currently recommended treatment of HCV infection) may be successful in patients with mild-to-moderate disease, but sustained responses are uncommon. In case of severe and rapidly progressive disease, although it is capable of suppressing viremia and cryoglobulinemia, antiviral therapy is not fully effective in controlling the inflammatory and self-perpetuating reaction consequent to the deposition of cryoglobulins in the glomeruli and vessel walls. In such cases, a short course of steroids and cytotoxic drugs (with or without plasmapheresis) may be needed to improve the vascular manifestations and decrease the production of cryoglobulins. Once the acute disease flare has been controlled, antiviral therapy may be administered to eradicate HCV, the causative agent of the cryoglobulinemic syndrome. In patients in whom antiviral therapy is ineffective, contraindicated or not tolerated, rituximab, a monoclonal anti-CD20 antibody, may be an alternative to standard immunosuppression.
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PMID:Hepatitis C virus-related cryoglobulinemia and glomerulonephritis: pathogenesis and therapeutic strategies. 1605 39

Rituximab is a genetically engineered chimeric monoclonal immunoglobulin (Ig)G1 antibody. It binds the CD20 trans-membrane surface antigen expressed by mature B cells but not by antibody secreting plasma cells, and removes the cells by activating complement, inducing cell-mediated lysis, and by apoptosis. Mainly used for the treatment of non-Hodgkin's lymphomas, rituximab has recently been tried with favourable responses in rheumatoid arthritis, systemic lupus erythematosus, and other chronic immunological diseases. Wegener's granulomatosis (WG) is a granulomatous vasculitis with high morbidity and mortality. It is thought that anti-neutrophil cytoplasmatic antibodies (ANCA) with specificity for proteinase 3 (PR3) are possibly involved in the pathogenesis of the disease. Conventional therapy with cyclophosphamide and corticosteroids generally succeeds in inducing remission, but relapses frequently follow. Among the biological agents, tumour necrosis factor-alpha (TNF-alpha) inhibitors have been tried with some success. Based on a case report we recently treated three refractory WG patients with rituximab and achieved almost complete but temporary remission. CD20+ cells disappeared rapidly in peripheral blood, only to rise prior to subsequent disease flares occurring at 34, 63, and 54 weeks, respectively (Figure 1). A new flare occurred in one patient at 86 weeks. At the end of the observation periods (54, 102, and 120 weeks), only one patient had proteinuria. Chest radiographs became normal in two patients, while infiltrates remained unchanged in the third. Granulomatous retro-orbital or sinus masses in two patients seemed unresponsive to therapy.
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PMID:Anti-CD20 therapy of treatment-resistant Wegener's granulomatosis: favourable but temporary response. 1613 30

Membranoproliferative glomerulonephritis (MPGN) associated with type II cryoglobulinemia is the predominant type of hepatitis C virus (HCV)-related glomerulonephritis. The blockade of the renin-angiotensin system, as well as a combined anti-HCV therapy that associates standard or pegylated alpha-interferon with ribavirin, are mandatory in all patients experiencing an HCV-related glomerulonephritis. In patients with nephrotic-range proteinuria and/or progressive renal failure, immunosuppressive therapy is necessary. Rituximab, the monoclonal anti-CD20 antibody that selectively targets the B cells, seems to be as least as efficient as cyclophosphamide. Because it is also better tolerated, it should be preferred to cyclophosphamide. During the acute phase, plasmapheresis and steroid pulses can be used. However, future prospective, controlled, and randomized studies are still required to establish evidence-based guidelines to treat HCV-related glomerulopathies.
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PMID:Treatment of hepatitis C-virus-related glomerulonephritis. 1651 28

We studied the clinical and immunological effects of Rituximab (anti-CD20) therapy in patients with lupus nephritis. In an open clinical trial, 22 patients with active systemic lupus erythematosis and renal involvement (mainly class III and IV according to the WHO classification) that was refractory to conventional therapy were studied. In all these patients, Rituximab (0.5 to 1.0 g at days 1 and 15) was added to the immunosuppressive therapy and its therapeutic effect was evaluated. In addition, the levels and function of regulatory T lymphocytes and the apoptosis of immune cells were assessed. We found a significant reduction in disease activity (p < 0.05, MEX-SLEDAI index), and proteinuria (p < 0.05) at days 60 and 90 of Rituximab therapy. Although most patients showed improvement in creatinine clearance and erythrocyturia, no significant changes in these parameters were detected. In most patients (20/22), B cell depletion was observed, but no clear-cut effect of Rituximab on complement levels or auto-antibody titers was detected (p > 0.05 in all cases). One patient died at day 70 with invasive histoplasmosis. No important adverse effects of Rituximab therapy were registered in other patients. A significant enhancement in the levels of different CD4+ regulatory cells (TREG, Th3, Tr1), but not CD8+ Ts lymphocytes, was observed at day 30. This increase was sustained for TREG cells at day 90, and accompanied by an improvement in their regulatory function. In addition, we observed an unexpected increase in the apoptosis of T cells at day 30. Interestingly, the enhancement in the suppressive function of TREG cells was not observed in the two patients that showed the poorest clinical response to Rituximab. We conclude that the data obtained in this open clinical trial suggest that Rituximab is a promising candidate for randomized controlled trials in patients with lupus nephritis refractory to the conventional immunosuppressive therapy. The effects of Rituximab on regulatory cells and apoptosis of T lymphocytes are interesting and its possible role in the putative effect of this biological agent in systemic lupus erythematosis deserves additional studies.
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PMID:Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. 1667 95


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