losartan-potassium and Lupus-Nephritis

Topics: Acute Kidney Injury; Autoantigens; Darbepoetin alfa; Diabetic Nephropathies; Erythropoietin; Glomerulonephritis, Membranous; Hematinics; Humans; Immunosuppressive Agents; Kidney Diseases; Lupus Nephritis; Randomized Controlled Trials as Topic; Renal Replacement Therapy

IL-17-producing CD4+ cells (TH17) are pathogenically linked to autoimmunity including to autoimmune kidney disease. Erythropoietin's (EPO) newly recognized immunoregulatory functions and its predominant intra-renal source suggested that EPO physiologically regulates TH17 differentiation, thereby serving as a barrier to the development of autoimmune kidney disease. Using in vitro studies of human and murine cells and in vivo models, we show that EPO ligation of its receptor (EPO-R) on CD4+ T cells directly inhibits TH17 generation and promotes trans-differentiation of TH17 into IL-17-FOXP3+CD4+ T cells. Mechanistically, EPO/EPO-R ligation abrogates upregulation of SGK1 gene expression and blocks p38 activity to prevent SGK1 phosphorylation, thereby inhibiting RORC-mediated transcription of IL-17 and IL-23 receptor genes. In a murine model of TH17-dependent aristolochic acid (ArA)-induced, interstitial kidney disease associated with reduced renal EPO production, we demonstrate that transgenic EPO overexpression or recombinant EPO (rEPO) administration limits TH17 formation and clinical/histological disease expression. EPO/EPO-R ligations on CD4+ T cells abrogate, while absence of T cell-expressed EPO-R augments, TH17 induction and clinical/histological expression of pristane-induced glomerulonephritis (associated with decreased intrarenal EPO). rEPO prevents spontaneous glomerulonephritis and TH17 generation in MRL-lpr mice. Together, our findings indicate that EPO physiologically and therapeutically modulate TH17 cells to limit expression of TH17-associated autoimmune kidney disease.

Topics: Animals; Aristolochic Acids; Cells, Cultured; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Female; Humans; Immediate-Early Proteins; Interleukin-17; Lupus Nephritis; Male; Mice; Mice, Inbred MRL lpr; Mice, Transgenic; Nephritis, Interstitial; Phosphorylation; Primary Cell Culture; Protein Serine-Threonine Kinases; Receptors, Erythropoietin; Receptors, Interleukin; Severity of Illness Index; T-Lymphocytes, Regulatory; Th17 Cells

An increasing body of data has shown that erythropoietin (EPO) plays multiple roles in inflammation control and immunoregulation. However, less attention has been given to its effects on lupus nephritis (LN). In this study, we investigated the therapeutic effects of EPO on LN in MRL/lpr mice, a well-studied animal model for lupus. MRL/lpr mice were randomly divided into an EPO and control group. Mice in the EPO group were treated with EPO; saline was given to the control group. Both groups were treated for 10 weeks. We analyzed the differences of general disease condition, histopathologic changes, Th lymphocytes subsets, and the expression of inflammatory factors of mice between the groups. Compared to the control group, mice in the EPO group showed less spleen hyperplasia, less urinary protein, and lower serum anti-dsDNA antibody; they also had lower renal histopathologic scores and less deposition of IgG/C3 within glomeruli. Moreover, Th1 and Th17 levels were decreased, while Th2 and Treg levels were increased in the spleen, and the expression of inflammatory cytokines decreased in both the spleen and kidneys. EPO increased Th2 and Treg lymphocytes, decreased Th1, Th17 lymphocytes in the spleen, and inhibited the inflammatory reactions in both the spleen and kidneys, thus ameliorating LN of MRL/lpr mice.

Topics: Animals; Cytokines; Erythropoietin; Inflammation; Kidney; Lupus Nephritis; Mice; Mice, Inbred MRL lpr; Proteinuria; Spleen; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Topics: Acute Kidney Injury; Adult; Blood Component Transfusion; Bone Marrow; Cell Lineage; Combined Modality Therapy; Darbepoetin alfa; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematuria; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Lymphohistiocytosis, Hemophagocytic; Male; Mycophenolic Acid; Myelodysplastic Syndromes; Pancytopenia; Pericarditis; Prednisone; Proteinuria; Recombinant Proteins

To study possible correction of bone disorders (osteopenia, Ca/P-imbalance, bone pain, limited volume of indolent movements) which are still a serious complication associated with renal diseases and pathogenic therapy (steroids).. The bone disorders were treated in 10 uremic hemodialyzed patients (8 men, 2 women; group 1) with vitamin D3 (calcitriol made in Russia) + rhEPO (recormon; Boehringer Mannheim), in 15 patients (15 women, 0 men) with lupus-nephritis (group 2) with vitamin D3 (n = 5, group 2a) or miscalcic (Sandoz) (n = 10, group 2b), in 2 patients (2 men, 0 women) with glomerulonephritis (group 3) with vitamin D3 + miacalcic. Additionally all the patients received Ca salts. In groups 2 and 3 renal function was normal. The duration of the treatment was 3-6 months.. In all the groups we obtained an analgetic effect (attenuation of bone pain and more indolent movements), improvement of life quality, diminished need in analgetics, elevation of serum Ca level (p > 0.05).. Treatment of renal patients with bone affection with vitamin D3 and miacalcic has an analgetic effect, improves life quality.

Topics: Adult; Analgesics; Bone Diseases; Calcitonin; Calcium; Cholecalciferol; Drug Therapy, Combination; Erythropoietin; Female; Glomerulonephritis; Humans; Lupus Nephritis; Male; Middle Aged; Quality of Life; Recombinant Proteins; Renal Dialysis; Treatment Outcome; Uremia

Deposition of immune complexes (IC) is an important step in the pathogenesis of lupus nephritis. Impairment of IC-clearance contributes to the accumulation of IC. It may be partly attributed to decreased complement containing immune complex (ICC) binding by erythrocytic complement receptor 1 (ECR1). Stimulating erythropoiesis with recombinant human erythropoietin (rHuEPO) may enhance the IC-clearance as increasing ECR1 expression and/or functional activity. Ten anemic patients with lupus nephritis were treated with 50 IU rHuEPO (Eprex) per kg body weight three times a week during a five week period. ICC-binding capacity of ECR1 was determined with 125I-labelled, C3ib containing BSA-anti-BSA complexes. In addition to effective correction of anemia, indicated by increased red blood cell count (RBC), hemoglobin concentration and reticulocyte ratio, rHuEPO significantly improved decreased ECR1 functional (ICC-binding) activity in patients with lupus nephritis. This improvement correlated with the increase in reticulocyte ratio. Although patients were kept on their previous therapy during Eprex administration, their clinical condition also improved. That was shown by a decrease in Westergreen ratio, serum creatinine concentration and anti-dsDNA level and also by an increase in creatinine clearance. Results suggest a beneficial immune modulatory effect of rHuEPO in lupus nephritis.

Topics: Adolescent; Adult; Anemia; Antigen-Antibody Complex; Erythrocyte Count; Erythrocytes; Erythropoietin; Female; Hemoglobins; Humans; Lupus Nephritis; Receptors, Complement 3b; Recombinant Proteins; Reticulocyte Count

A 46-year-old man was admitted to our clinic because of acute heart failure. Six years before admission he was pointed out cardiomegary and hematuria. One year later, he was diagnosed as having jugular foramen syndrome. On admission, he had a fever and dyspnea. Pansystolic blowing murmur was audible at the apex. The chest ratio on his chest X-ray was 52.5%. An electrocardiogram showed left ventricular hypertrophy. An echocardiogram showed marked dilatation and severe dysfunction of left ventricle. Radionuclide scanning with technetium 99 m pyrophosphate identified inflammatory change in the apex. Myocardial biopsy showed fibrotic degeneration and IgG deposits in myocardium. Blood examination showed anemia, lymphopenia. positive anti-nuclear antibody (1000 times, shaggy pattern), positive anti ds-DNA antibody and hypocomplementemia. Furthermore, proteinuria was pointed out. Renal biopsy showed focal segmental glomerulonephritis with active necrotizing lesion (type III nephritis). Lupus myocarditis and nephritis was diagnosed. After prednisolone (80 mg/day) was administered. left ventricular function and hypocomplementemia improved. The ACE inhibitor was also used for proteinuria. In spite of a little amount of blood transfusion, he showed hepatic hemosiderosis. We suspect that the cause of hemosiderosis was related chronic inflammation of active lupus. It was treated with Erythropoietin.

Topics: Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Cranial Nerve Diseases; Erythropoietin; Hemosiderosis; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Male; Middle Aged; Myocarditis; Polyneuropathies; Prednisolone; Syndrome

Topics: Anemia; Child; Erythropoietin; Female; Humans; Immunization, Passive; Immunoglobulins; Injections, Intravenous; Kidney Failure, Chronic; Lupus Nephritis; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins

Recombinant human erythropoietin (r-HuEPO) is broadly accepted as treatment for anemia in dialysis and nondialysis patients with chronic renal failure, but data regarding the safety and efficacy of this drug in pregnancy are limited. Maternal and fetal problems have been reported to be associated with anemia during pregnancy. On the other hand, anemia is a frequent feature of systemic lupus erythematosus. We report the successful use of r-HuEPO in a young woman with lupus nephritis complicated by severe anemia during pregnancy. Additional studies should be encouraged to confirm the safety of r-HuEPO therapy during pregnancy.

Topics: Adult; Anemia; Erythropoietin; Female; Hematocrit; Humans; Lupus Nephritis; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Recombinant Proteins

A male patient suffered chronic renal failure due to lupus nephritis and was undergoing hemodialysis. Six years after beginning hemodialysis, anemia developed, which improved by erythropoietin. Unresponsiveness to erythropoietin gradually appeared, and with a suspicion of pure red cell aplasia, he was treated with a high-dose corticosteroid but the unresponsiveness did not improve. Neither his serum nor lymphocytes inhibited erythropoiesis of either normal bone marrow stem cells or his own in vitro. These observations suggest an impaired hematopoietic microenvironment in his bone marrow.

Topics: Adrenal Cortex Hormones; Adult; Chronic Disease; Colony-Forming Units Assay; Drug Therapy, Combination; Erythropoiesis; Erythropoietin; Humans; Kidney Failure, Chronic; Lupus Nephritis; Male; Red-Cell Aplasia, Pure; Renal Dialysis