losartan-potassium and Vasculitis

Rituximab, a monoclonal antibody directed against the CD20 molecule found on pre-B cells and mature B cells (but not on plasma cells), was introduced in the late 1990s for the treatment of non-Hodgkin's lymphoma. Recently, this antibody has been used to treat autoimmune diseases, especially those associated with a prominent humoral component and with potentially pathogenic autoantibodies. Small cohort studies have indicated that rituximab could have an important role in the management of these disorders. Rituximab has also been utilized in the transplant setting, to diminish levels of alloreactive antibodies in highly sensitized patients, to manage ABO-incompatible transplants, and to treat rejection associated with B cells and antibodies. The exact mechanism by which rituximab exerts its effects in autoimmunity and transplantation remains unclear, as specific autoantibody or alloantibody levels often seem not to diminish in parallel with clinical improvement. A role for rituximab in depleting B cells and compromising their antigen-presenting function seems likely; rituximab might also inhibit T-cell activation. A synergistic effect has been noted in vitro following administration of corticosteroids to B-cell lines, with accentuation of B-cell cytotoxicity; this observation might be relevant to certain studies, as some regimens have utilized both agents simultaneously. This article reviews the current use of rituximab in renal disease and transplantation, and includes discussion of the drug's potential role in novel therapeutic protocols.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; Erythropoietin; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Graft Rejection; Humans; Immunologic Factors; Kidney Diseases; Kidney Transplantation; Lupus Erythematosus, Systemic; Lymphoproliferative Disorders; Recombinant Proteins; Red-Cell Aplasia, Pure; Rituximab; Vasculitis

Topics: Alopecia; Cytokines; Dermatitis, Exfoliative; Drug Eruptions; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interferons; Interleukin-2; Tumor Necrosis Factor-alpha; Vasculitis; Vitiligo

Topics: Combined Modality Therapy; Comorbidity; Diet, Protein-Restricted; Diet, Sodium-Restricted; Disease Progression; Drug-Related Side Effects and Adverse Reactions; Erythropoietin; Humans; Hypertension; Kidney Diseases; Kidney Failure, Chronic; Kidney Function Tests; Prognosis; Renal Dialysis; Vasculitis; Water-Electrolyte Balance

1. Recombinant human erythropoietin (rHuEPO) has been used for the management of renal anaemia. Recent studies suggest pleiotropic properties of rHuEPO in various tissues. The aim of the present study was to investigate the vasoprotective effects of rHuEPO in renal failure rats. 2. Rats subjected to 5/6 and 17/18 nephrectomy (5/6Nx and 17/18Nx rats, respectively) were treated with rHuEPO (75 U/kg, s.c.) three times a week for 2 weeks. 3. Administration of rHuEPO to 5/6Nx or 17/18Nx rats had no effect on systolic blood pressure or decreased haematocrit. However, rHuEPO treatment normalized proteinuria and creatinine clearance in 5/6Nx, but not in 17/18Nx, rats. 4. Vasodilation in response to acetylcholine in aortic rings was impaired in 5/6Nx and 17/18Nx rats and improved by rHuEPO in both groups. Immunohistochemical analysis revealed that macrophage infiltration into adventitial areas and the expression of osteopontin were enhanced in aortas from 5/6Nx and 17/18Nx rats, but that rHuEPO suppressed these effects. In addition, rHuEPO attenuated medial hyperplasia and NADPH oxidase-derived superoxide production in 5/6Nx and 17/18Nx rats. 5. Activation of the Akt signalling pathway was evident in rHuEPO-treated rats as the increased expression of phosphorylated Akt and glycogen synthase kinase-3β. Treatment with rHuEPO restored the expression of phosphorylated endothelial nitric oxide synthase in the aorta and urinary excretion of NO(x) in nephrectomized rats. 6. These results suggest that a low dose of rHuEPO results in the normalization of endothelial function, vascular inflammation and oxidative stress in rats with renal ablation beyond haematopoiesis. In addition, these vasoprotective effects are observed even in a state of deteriorating renal dysfunction.

Topics: Acetylcholine; Animals; Aorta, Thoracic; Blood Pressure; Creatinine; Erythropoietin; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hematocrit; Hematopoiesis; Humans; Hyperplasia; Macrophages; Male; NADPH Oxidases; Nephrectomy; Nitric Oxide; Nitric Oxide Synthase Type III; Nitroprusside; Osteopontin; Oxidative Stress; Proteinuria; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Recombinant Proteins; Superoxides; Vasculitis; Vasodilation

The association between myelodysplastic syndromes (MDS) and autoimmune manifestations is not uncommon. As a rule, autoimmune abnormalities follow the diagnosis of MDS. We describe here a patient with MDS who developed a striking spectrum of diverse autoimmune disorders, including dermatitis, polyarthritis, and vasculitis, which preceded the clinical appearance of MDS.

Topics: Aged; Aged, 80 and over; Arthritis; Autoimmune Diseases; Blood Transfusion; Combined Modality Therapy; Dermatitis; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Filgrastim; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Male; Methylprednisolone; Myelodysplastic Syndromes; Recombinant Proteins; Risk Assessment; Severity of Illness Index; Treatment Outcome; Vasculitis

Topics: Adult; Cyclophosphamide; Erythropoietin; Female; Humans; Hypertension; Male; Radioimmunoassay; Time Factors; Vasculitis

Topics: Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Drug Resistance; Erythropoietin; Female; Humans; Middle Aged; Renal Dialysis; Vasculitis

Topics: Erythropoietin; Gout; Humans; Male; Middle Aged; Pain; Syndrome; Toes; Vasculitis