losartan-potassium and Glomerulonephritis

Glomerulonephritis (GN) is a form of autoimmunity in which apoptosis may be a double-edged sword. Resolution of GN can be promoted by apoptosis of infiltrating leucocytes and excess resident glomerular cells, leading to efficient anti-inflammatory clearance by macrophages and mesangial cells. However, unscheduled apoptosis in glomerular cells, especially epithelial cells ('podocytes') may drive progression of GN to hypocellular, nonfunctional scar. Defects in clearance of apoptotic cells may also have deleterious local effects, in addition to promoting autoimmunity itself. Nevertheless, there is strong promise for novel therapies based on new knowledge of apoptosis in GN, especially in regulation of leucocyte clearance from the inflamed glomerulus.

Topics: Animals; Apoptosis; Endothelial Cells; Epithelial Cells; Erythropoietin; Extracellular Matrix; Glomerular Mesangium; Glomerulonephritis; Humans; Kidney Glomerulus; Phagocytosis

Somatic cell gene therapy has made considerable progress last five years and has shown clear success in some clinical trials. In the field of nephrology, both the elucidation of pathophysiology of renal diseases and the development of gene transfer technique have become driving force for new therapy of incurable renal diseases, such as Alport syndrome and polycystic kidney disease. Gene therapy of renal cancer, although its application is limited to advanced cancer, is the front-runner of clinical application. Erythropoietin gene therapy has provided encouraging results for the treatment of anemia in uremic rats and recently progressed to the inducible one in response to hypoxia. Gene therapy for glomerulonephritis and renal fibrosis showed prominent impact on experimental models, although the safety must be confirmed for prolonged treatment. Transplant kidney is an ideal material for gene modification and induction of tolerance in the transplant kidney is an attractive challenge. Emerging techniques are becoming available such as stem cell technology and messenger RNA silencing strategies. We believe that the future of gene therapy research is exciting and promising and it holds an enormous potential for clinical application.

Topics: Adenoviridae; Anemia; Erythropoietin; Fibrosis; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Glomerulonephritis; Humans; Kidney Diseases; Kidney Transplantation; Lentivirus; Polycystic Kidney Diseases; Recombinant Proteins

Topics: Age Factors; Databases, Factual; Diabetic Nephropathies; Diet, Protein-Restricted; Erythropoietin; Female; Glomerulonephritis; Humans; Internet; Japan; Kidney Failure, Chronic; Male; Morbidity; Prognosis; Reference Standards; Renal Dialysis; Sex Factors; Time Factors

Topics: Anemia; Animals; Bone Marrow; Bone Marrow Cells; Cyclic AMP; Cytoplasm; Erythropoietin; Glomerulonephritis; Hematopoietic System; Humans; Liver; Polycythemia; Reticulocytes; RNA; Sheep; Spleen; Uremia

Topics: Animals; Antibodies; Dogs; Erythropoietin; Fluorescent Antibody Technique; Glomerulonephritis; Graft Rejection; Haplorhini; Histocompatibility; Humans; Immunoglobulins; Immunosuppression Therapy; Immunosuppressive Agents; Kidney; Kidney Transplantation; Macaca; Neoplasms; Pan troglodytes; Papio; Renin; Transplantation Immunology; Transplantation, Autologous; Transplantation, Heterologous; Transplantation, Homologous

To study the effect of treatment of renal anemia by combination of Bushen Jianpi Recipe (BJR, a Chinese experience recipe for supplementing Shen and supporting Pi) and low dosage erythropoietin (EPO), and the influence of treatment on change of serum tumor necrosis factor alpha (TNF-alpha) so as to explore the possible mechanism of integrative Chinese and western medicine (ICWM) in treating renal anemia.. Patients with renal anemia were randomly divided into two groups, the ICWM group and the control group, symptomatic and supporting treatment such as dialysis, supplementing of ferrous, foliac acid and vitamin B12, was given to both groups. Additionally, to the ICWM group, 50 IU/kg of EPO subcutaneous injection for twice every week, and oral intake of BJR, one dose per day taken in two parts, were given, and to the control group, EPO alone, 50 IU/kg by subcutaneous injecting, 3 times per week, was given. The therapeutic course for two groups was 3 months. Blood levels of hemoglobin (Hb), hematocrit (Hct), TNF-alpha were measured before treatment and the therapeutic effect was observed.. After treatment, the levels of Hb and Hct increased significantly in both groups (P < 0.01), comparison between the two groups in Hb and Hct after being treated for 3 months showed significant difference (P < 0.05). The serum level of TNF-alpha was markedly higher than normal range in both groups before treatment, it significantly lowered after treatment in the ICWM group (P < 0.05), but unchanged in the control group.. Combination of BJR and EPO could significantly inhibit the production of TNF-alpha, this may be an important factor for ICWM in effectively improving sensitivity to EPO.

Topics: Adult; Anemia; Chronic Disease; Drug Therapy, Combination; Drugs, Chinese Herbal; Erythropoiesis; Erythropoietin; Female; Glomerulonephritis; Humans; Male; Middle Aged; Phytotherapy; Recombinant Proteins; Tumor Necrosis Factor-alpha

Cytosolic free calcium ([Ca(2+)](i)) is an important second messenger during stimulation in a wide variety of cells, including polymorphonuclear leukocytes (PMNs). Its mobilization in PMNs is altered in various diseases such as atherosclerosis and ageing. In chronic haemodialysis (HD) patients, both atherosclerosis and accelerated ageing are well known. Therefore [Ca(2+)](i) in resting PMNs of HD patients was determined along with certain parameters which might affect it, such as recombinant human erythropoietin (rHuEpo) treatment, calcium-phosphate balance, and biocompatibility of dialysis membranes.. PMNs were separated by density centrifugation and [Ca(2+)](i) was determined by spectrofluorimetry using Quin 2/AM fluorescent dye. Laboratory parameters were determined by standard methods in clinical chemistry.. It was found that [Ca(2+)](i) in resting PMNs of HD patients not undergoing rHuEpo therapy was higher than that of controls. After 12-weeks of rHuEpo therapy, [Ca(2+)](i) decreased to near normal level. The role of erythropoiesis in normalization of [Ca(2+)](i) in resting PMNs was supported by PMN [Ca(2+)](i) which was elevated in patients who had low haemoglobin (<100 g/l) or haematocrit (<0.30) values. In some patients, including those receiving rHuEpo treatment, [Ca(2+)](i) remained high, suggesting a role for other parameters in increasing [Ca(2+)](i). One possible parameter might be the disturbed calcium-phosphate metabolism of chronic renal failure, because we found a strong correlation between [Ca(2+)](i) and plasma iPTH levels in HD patients (r=0.743, P<0.001). [Ca(2+)](i) was also elevated in PMNs of those patients who had either low plasma calcium or high plasma phosphate levels. PMN [Ca(2+)](i) of HD patients correlated positively with the duration of HD (r=0.671, P<0.001). However, there was no correlation between [Ca(2+)](i) and patient age. The dialysis procedure itself also transiently increased PMN [Ca(2+)](i) HD patients, independently of the type of dialysis membrane.. PMN [Ca(2+)](i) is modulated by various parameters in HD patients, including the degree of anaemia, disturbances of calcium metabolism, and duration of dialysis treatment. The elevated [Ca(2+)](i) of resting PMNs might contribute to altered functions in these cells.

Topics: Adult; Arteriosclerosis; Blood Cell Count; Calcium; Cytosol; Erythropoiesis; Erythropoietin; Glomerulonephritis; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Membranes, Artificial; Neutrophils; Parathyroidectomy; Recombinant Proteins; Regression Analysis; Renal Dialysis

High-flux haemodialysis (HD) has recently been vigorously promoted as a novel standard, and it can indeed efficiently reduce the occurrence of most uraemic symptoms due to middle molecular toxins and/or underdialysis. However, some symptoms remain problematical, particularly peripheral polyneuropathy (PPN). One of the possible reasons for this is that the patients may have low concentrations of some nutrients, e.g. vitamin B(6), necessary for normal peripheral neuron function.. Predialysis serum pyridoxal-5'-phosphate (P5P) level was determined in 36 chronic HD patients who were undergoing high-flux HD and receiving human recombinant erythropoietin. Among them, 26 patients suffered from PPN. Prior to supplementation, these 26 patients were examined and their neurological symptoms were ranked according to our PPN symptom score. Vitamin B(6) (60 mg/day) was randomly prescribed to 14 of them, and vitamin B(12) (500 microg/day) was prescribed to the others. After 4 weeks, all the patients were re-examined.. We found that predialysis serum P5P levels of HD patients with PPN were not significantly lower than those of matched HD patients without PPN. Nonetheless, it was demonstrated that supplementation with vitamin B(6) for 4 weeks significantly increased the predialysis level of P5P and dramatically attenuated PPN symptoms compared with initial symptoms. No improvement was observed in response to vitamin B(12) supplementation.. This result suggests that although vitamin B(6) deficiency could not be demonstrated in patients with chronic renal failure on high-flux HD, vitamin B(6) supplementation was effective in improving PPN symptoms of various aetiologies, possibly because of vitamin B(6) resistance to PPN in these patients.

Topics: Chronic Disease; Diabetic Neuropathies; Erythropoietin; Female; Glomerulonephritis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Polyneuropathies; Pyridoxal Phosphate; Pyridoxine; Recombinant Proteins; Renal Dialysis; Vitamin B 12

Impaired immunological response in hemodialysis (HD) patients, which leads to inappropriate cytokine production, is partially caused by the hyperstimulation of both T lymphocytes and monocytes/macrophages. Recent data suggest that human recombinant erythropoietin (rhEPO) may have an immunological action. The goal of our study was to estimate the influence of rhEPO treatment on the production of the inflammatory cytokine tumor necrosis factor alpha (TNFalpha) and antiinflammatory cytokin interleukin-10 (IL-10) in 10 HD patients receiving rhEPO for 6 months. The levels of cytokines were measured in the in vitro cultures of whole blood. The level of IL-10 increased in all treated patients during the therapy, and it was accompanied by a transitory decrease of TNFalpha. The results of our studies suggest that rhEPO may reduce the inflammatory process by decreasing production of TNFalpha and increasing production of IL-10.

Topics: Adult; Blood Cells; Cells, Cultured; Erythropoietin; Female; Glomerulonephritis; Humans; Interleukin-10; Kidney Failure, Chronic; Male; Middle Aged; Phytohemagglutinins; Polycystic Kidney Diseases; Pyelonephritis; Recombinant Proteins; Renal Dialysis; Tumor Necrosis Factor-alpha

Recombinant human erythropoietin (rHuEPO) was administered to males undergoing hemodialysis, and its effects on penile erection and hypothalamus-pituitary-gonadal hormone levels were studied. The subject consisted of 18 males undergoing hemodialysis ranging in age from 22 to 58 years (mean 45.3 years). Chronic glomerulonephritis was present in 16, and diabetic nephropathy in 2, as underlying disease. rHuEPO was administered intravenously at 1,500 U 3 times a week with a target to increase the Ht value to 25% or above. Penile erection was evaluated subjectively by a questionnaire based on a visual analogue scale and objectively by semi quantitative measurement of nocturnal penile tumescence (NPT) using an erectometer. Of the 18 patients, subjective improvements in penile erection were observed in 13 (72%), and objective improvements in NPT were observed in 10 (56%). The administration of rHuEPO may alleviate hyperprolactinemia but was found to have no effect on the FSH, LH, Zn, or HS-PTH level. rHuEPO was suggested to be fairly effective for the treatment of sexual disorders.

Topics: Adult; Chronic Disease; Diabetic Nephropathies; Erectile Dysfunction; Erythropoietin; Glomerulonephritis; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Penile Erection; Recombinant Proteins; Renal Dialysis; Testis

Although erythropoiesis-stimulating agents (ESAs) exert renoprotective effects in renal disease models, it has not been revealed whether the prolonged duration of action of ESAs contributes to their renoprotective effects.. We examined whether the prolonged duration of ESAs' action contributes to their renoprotective effects by comparing a divided administration of a short-acting ESA, epoetin beta (EPO), or a single administration of a long-acting ESA, epoetin beta pegol (continuous erythropoietin receptor activator; C.E.R.A.), to a single administration of EPO in chronic glomerulonephritis (GN) rats.. Chronic GN was induced by intravenous injection of anti-Thy 1.1 antibody (0.6 mg/kg) into uninephrectomized rats (day 0). Chronic GN rats were intravenously injected once with vehicle (disease control; DC), EPO 5,000 IU/kg (single EPO), or C.E.R.A. 25 μg/kg (single C.E.R.A.) on day 1; or 3 times during the first week with EPO 1,667 IU/kg from day 1 (divided EPO; total 5,000 IU/kg). Hemoglobin (Hb) level and urinary total protein (U-TP) level which are the indexes of hematopoiesis and renoprotective effects, respectively, were measured several times over 8 weeks.. Divided EPO and single C.E.R.A. increased Hb levels more greatly than did single EPO. In all chronic GN rats, elevated U-TP levels decreased transiently 2 weeks after chronic GN induction and then flared again. Single EPO significantly suppressed this exacerbation of U-TP levels compared to DC. Divided EPO and single C.E.R.A. each significantly suppressed the exacerbation of U-TP levels compared to single EPO.. Prolonged duration of ESAs' action contributed significantly to their renoprotective effects.

Topics: Anemia; Animals; Disease Models, Animal; Disease Progression; Drug Administration Schedule; Erythropoiesis; Erythropoietin; Glomerulonephritis; Hematinics; Hemoglobins; Hypoxia; Injections, Intravenous; Iron; Isoantibodies; Kidney; Male; Polyethylene Glycols; Protective Agents; Proteinuria; Rats, Inbred F344; Recombinant Proteins

Glomerulonephritis (GN) develops via accumulation of extracellular matrix through macrophage recruitment in glomeruli. It is unclear whether epoetin beta pegol (continuous erythropoietin receptor activator, CERA), a long-acting erythropoiesis-stimulating agent, exerts a renoprotective effect by preventing glomerulosclerosis. We examined the renoprotective effect of CERA in rats with Thy-1 glomerulonephritis (Thy-1-GN), an animal model for mesangial proliferative glomerulonephritis.. Thy-1-GN was induced in F344 rats by injection of anti-Thy1.1 antibody. CERA (25 µg/kg) was intravenously administered 4 h before anti-Thy1.1 antibody injection. After 6 days, blood and urine was collected for biochemical analysis and kidneys harvested for analysis of histopathology and mRNA expression.. In Thy-1-GN rats, CERA suppressed increased urinary total protein, urea nitrogen, and N-acetyl-β-(D)-glucosaminidase. CERA significantly prevented glomerulosclerosis and expression of α-smooth muscle actin, collagen-1, and fibronectin. Increased macrophage infiltration and up-regulated monocyte chemotactic protein-1 were significantly suppressed by CERA. Furthermore, CERA also suppressed up-regulation of arginase-1, a marker of M2 macrophages. Arginase-1 expression levels strongly correlated with levels of collagen-1 and fibronectin mRNA.. These results suggest that CERA has potential to protect kidney function through the prevention of glomerulosclerosis, accompanied by prevention of M2 macrophage recruitment.

Topics: Acetylglucosaminidase; Actins; Animals; Arginase; Blood Urea Nitrogen; Cell Movement; Chemokine CCL2; Collagen Type I; Disease Models, Animal; Erythropoietin; Fibronectins; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Isoantibodies; Ki-67 Antigen; Macrophages; Male; Polyethylene Glycols; Proteinuria; Rats; Rats, Inbred F344; RNA, Messenger; Tumor Necrosis Factor-alpha

To evaluate the efficiency of treatment for renal anemia in patients with chronic glomerulonephritis (CGN), by using erythropoietin and its combination with hypoxic altitude chamber training (HACT).. Sixty-three patients (41 men and 22 women) (mean age 37.1 ± 3.3 years) with CGN during the predialysis phase of chronic kidney disease (CKD) complicated by anemia. Hemoglobin (Hb), packed cell volume (PCV), and red blood cell indices (mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC)), platelet count, serum iron, fibrinogen, C-reactive protein (CRP) and creatinine levels were determined in all the patients at baseline and during a prospective follow-up. Glomerular filtration rate (GFR) was measured using with the Rehberg-Tareev test. Along with standard renal protective therapy, all the patients received either epoetin beta (n=31; Group 1) or its combination with HACT (n=32; Group 2). In Group 1 patients (n=31), erythropoietin (EPO) was given in an initial dose of 20-50 IU/kg thrice daily, followed by the dose being adjusted until the target Hb level was reached. Group 2 patients (n=32) received HACT cycles by the standard procedure in combination with EPO given in lower doses (20-50 IU/kg once weekly). A prospective .follow-up of the patients was carried out during one year.. Following one year, the number of patients who had achieved the target Hb level was 74.1% in Group 1 and 87.5% in Group 2. Over time, there were increases in the concentration of Hb (from 108.6 ± 19.4 to 124.5 ± 14.09 g/l; p<0.05), PCV, and red blood cell indices (MCV, MCHC) in the patients receiving EPO (Group 1). Besides an'anti-anemic effect, there was a significant decrease in the concentrations of fibrinogen from 6655 (4884-7634) to 3776 (3330-4884) mg/dL; (p<0.05), serum creatinine from 159 (89--261) to 138 (79-258) pmol/I (p<0,05), proteinuria from 2.955 (1.024-6.745) to 2.069 (0.539-4.279) (p<0.05), which was accompanied by an increase in GFR from 62.3 (37.0 - 107.4) to 76.9 (46.0-96.0) mi/min (p<0.05). In Group 2, the rise in the concentration of Hb (from 114.1 ± 11.7 to 132.0 ± 16.5 g/I (p<0.05), PCV, MCV, and MCHC proved to be more pronounced than that in Group 1 (p<0.05) and accompanied by an elevation in the counts of platelets (from 222.7 ± 19.8.10(9)/1 to 249.3 ± 21.9.10(9)/1 (p<0:05)) and red blood cells (from 4.0 ± 0.4-10(12)/1 to 4.34 ± 0.3 X 10(12)/I (p<0.05)). There was a more marked reduction in the degree of proteinuria from 3.092 (0.764-7.694) g at baseline to 1.600 (0.677-4.078) g one year later (p<0.05) than that in Group 1 (p<0.05). The increase in GFR from 60.1 (46.0-96.0) to 79.4 (44.0-120.0) ml/min (p<0.05) and the fall in the concentration of fibrinogen from 5555 (4884-7770) to 4107 (3776-5328) mg/dL (p<0.05) and serum creatinine from 166 (92-273) to 147 (92-152) μmol/L (p<0.05), which were observed in Group 2, were comparable to those in Group 1.. Epoetin beta used in patients with CGN has an anti-anemic effect and leads to improved renal nitrogen-excretory function. Erythropoietin in combination with HACT used in CGN provides a higher anti-anemic efficacy and a more pronounced antiproteinuric effect.

Topics: Adult; Anemia; Atmosphere Exposure Chambers; Chronic Disease; Combined Modality Therapy; Erythropoietin; Female; Glomerulonephritis; Humans; Hypoxia; Male; Middle Aged; Respiratory Therapy; Treatment Outcome

Anemia can contribute to chronic allograft injury by limiting oxygen delivery to tissues, particularly in the tubulointerstitium. To determine mechanisms by which erythropoietin (EPO) prevents chronic allograft injury we utilized a rat model of full MHC-mismatched kidney transplantation (Wistar Furth donor and Lewis recipients) with removal of the native kidneys. EPO treatment entirely corrected post-transplant anemia. Control rats developed progressive proteinuria and graft dysfunction, tubulointerstitial damage, inflammatory cell infiltration, and glomerulosclerosis, all prevented by EPO. Normalization of post-transplant hemoglobin levels by blood transfusions, however, had no impact on chronic allograft injury, indicating that EPO-mediated graft protection went beyond the correction of anemia. Compared to syngeneic grafts, control allografts had loss of peritubular capillaries, higher tubular apoptosis, tubular and glomerular oxidative injury, and reduced expression of podocyte nephrin; all prevented by EPO treatment. The effects of EPO were associated with preservation of intragraft expression of angiogenic factors, upregulation of the anti-apoptotic factor p-Akt in tubuli, and increased expression of Bcl-2. Inhibition of p-Akt by Wortmannin partially antagonized the effect of EPO on allograft injury and tubular apoptosis, and prevented EPO-induced Bcl-2 upregulation. Thus non-erythropoietic derivatives of EPO may be useful to prevent chronic renal allograft injury.

Topics: Anemia; Animals; Apoptosis; Biomarkers; Blood Transfusion; Chronic Disease; Erythropoietin; Glomerulonephritis; Hematinics; Hemoglobins; Histocompatibility; Kidney; Kidney Diseases; Kidney Transplantation; Mice; Primary Graft Dysfunction; Proteinuria; Rats; Rats, Inbred Lew; Rats, Inbred WF; Time Factors

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Monoclonal; Erythropoietin; Female; Glomerulonephritis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunosuppressive Agents; Middle Aged; Therapies, Investigational

Recent studies have demonstrated that erythropoietin (EPO) and its analogs induce cytoprotective effects on many nonerythroid cells. In this study, we examined whether darbepoetin-α might prevent glomerular lesions in the Thy-1.1 model of glomerulonephritis (Thy-1-GN). GN was induced in Wistar rats by a single injection of monoclonal anti-Thy-1.1 antibody. Rats were killed at 24 h, 72 h, 7 days, 10 days, or 15 days after antibody injection. Kidneys were removed for histological analysis, and proteinuria was measured. Because at day 7 the maximal degree of renal damage and proteinuria was found, the effect of darbepoetin-α was tested at day 7 and two different protocols of administration were used; After anti-Thy-1.1 injection, rats received two doses of darbepoetin-α or vehicle at days 0 and 4 or at days 4 and 6. At day 7, proteinuria, plasma creatinine concentration, and renal morphology analysis were performed. Also, α-actin, desmin, caspase-3, and Ki67 protein expression were evaluated by immunohistochemistry. Our results showed that in both protocols of administration, darbepoetin-α treatment decreased proteinuria in Thy-1-GN rats and this effect correlated with the improvement in renal morphology. Glomerular lesions, α-actin, and caspase-3 protein expression, observed in most glomeruli of Thy-1-GN rats, were significantly reduced in darbepoetin-α-treated rats, while cell proliferation was significantly enhanced. The results indicate that darbepoetin-α treatment promotes glomerular recovery.

Topics: Animals; Caspase 3; Darbepoetin alfa; Disease Models, Animal; Erythropoietin; Glomerulonephritis; Isoantibodies; Kidney Glomerulus; Male; Proteinuria; Rats; Rats, Wistar; Regeneration

The recombinant human erythropoietin (rhEPO) is used for the treatment of patients with renal anemia. However, rhEPO should be administered subcutaneously or intravenously three times a week. The repetitive injections of rhEPO result in burdens to patients. To resolve this problem, we investigated the sustaining release methods using an rhEPO-hydroxyapatite (HAp) made by spray-drying technique as the drug delivery system. Two types of rhEPO-HAp formulations were prepared; zinc (Zn) formulation and Zn and poly-L-lactic acid (PLA) formulation. These formulations were examined in genetically anemic model, ICGN (ICR-derived glomerulonephritis) mice. According to in vivo release test of rhEPO from HAp in ICGN mice, elevated plasma concentration of rhEPO could be maintained for more than 7 days. These mice showed the amelioration of anemia for more than 3 weeks post-administration without causing any side effect. In conclusion, Zn or Zn/PLA formulation of HAp was considered to be one of the useful carriers of rhEPO for long-term improvement of anemia.

Topics: Anemia; Animals; Delayed-Action Preparations; Durapatite; Erythropoietin; Glomerulonephritis; Humans; Mice; Mice, Inbred Strains; Recombinant Proteins; Specific Pathogen-Free Organisms; Time Factors

Light chain deposit disease is a plasma cell disorder characterized by production of a large amount of monoclonal immunoglobulin light chain or part of it, which is usually deposited as an amorphous substance in the kidneys. Immunotactoid glomerulopathy is an uncommon disease, which might be related to plasma cell dyscrasia, and characteristically manifest as organized glomerular ultra structural fibrils or microtubules. In this article, we report a case of a combined presentation of light chain disease and immunotactoid glomerulopathy in a patient with multiple myeloma and reversible advanced renal failure.

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Cholecalciferol; Erythropoietin; Glomerular Filtration Rate; Glomerulonephritis; Humans; Immunoglobulin kappa-Chains; Immunoglobulin Light Chains; Kidney Glomerulus; Male; Middle Aged; Recombinant Proteins; Treatment Outcome

Detachment or apoptosis of podocytes leads to proteinuria and glomerulosclerosis. There are no current interventions for diabetic or non-diabetic glomerular diseases specifically preventing podocyte apoptosis. Binding of erythropoiesis stimulating proteins (ESPs) to receptors on non-hematopoietic cells has been shown to have anti-apoptotic effects in vitro, in vivo, and in preliminary human studies. Recently, erythropoietin receptors were identified on podocytes; therefore, we tested effects of darbepoetin alfa in preventing podocyte apoptosis. Cultured immortalized mouse podocytes were treated with low-dose ultraviolet-C (uv-C) irradiation to induce apoptosis in the absence or presence of darbepoetin alfa. Apoptosis was quantified by Hoechst staining and by caspase 3 cleavage assessed by Western blots. Pretreatment with darbepoetin alfa significantly reduced podocyte apoptosis with this effect involving intact Janus family protein kinase-2 (JAK2) and AKT signaling pathways. Additionally, darbepoetin alfa was found protective against transforming growth factor-beta1 but not puromycin aminonucleoside induced apoptosis. Mice with anti-glomerular antibody induced glomerulonephritis had significantly less proteinuria, glomerulosclerosis, and podocyte apoptosis when treated with darbepoetin alfa. Our studies show that treatment of progressive renal diseases characterized by podocyte apoptosis with ESPs may be beneficial in slowing progression of chronic kidney disease.

Topics: Animals; Antibodies; Apoptosis; Autoantibodies; Cell Proliferation; Cells, Cultured; Darbepoetin alfa; Disease Models, Animal; Disease Progression; Erythropoietin; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Janus Kinase 2; Mice; Podocytes; Protective Agents; Proteinuria; Proto-Oncogene Proteins c-akt; Puromycin Aminonucleoside; Receptors, Erythropoietin; Signal Transduction; Transforming Growth Factor beta1; Ultraviolet Rays

The ICR-derived glomerulonephritis (ICGN) mouse is an appropriate model for anemia associated with chronic renal disorder (CRD). Insufficient renal production of erythropoietin (EPO) induces the anemia associated with CRD. EPO mRNA is expressed in both kidneys and liver of progressing-stage ICGN mice. Hypoxic stimulation induced the EPO mRNA expression in the liver as well as in the kidneys of ICGN mice. The localization of EPO-producing cells in the liver remains controversial. Present study using an amplified in situ hybridization technique identified that nonparenchymal cells were the source of hepatic EPO production in ICGN mice under both normoxia and hypoxia.

Topics: Animals; DNA Primers; Erythroid Precursor Cells; Erythropoietin; Glomerulonephritis; In Situ Hybridization; Kidney; Liver; Mice; Mice, Inbred Strains; Reverse Transcriptase Polymerase Chain Reaction

We previously demonstrated that chronic hypoxia has pivotal roles in the progression of tubulointerstitial injury from the early stage of the uninephrectomized Thy1 nephritis model. We have also shown that pretreatment of cobalt confers renoprotection in the ischemia/reperfusion (I/R) injury, in association with the up-regulation of hypoxia-inducible factor (HIF)-regulated genes. Here, we tested the hypothesis that cobalt administration not only attenuates acute ischemic insult, but also ameliorates tubulointerstitial injury secondary to chronic hypoxia.. We applied sustained cobalt treatment to the uninephrectomized Thy1 nephritis model at 3 to 5 weeks, when tubular hypoxia appeared. Histologic evaluation, including glomerular and peritubular capillary networks, was made at 8 weeks. HIF activation was confirmed by real-time polymerase chain reaction (PCR) analyses for HIF-regulated genes, such as erythropoietin (EPO), vascular endothelial growth factor (VEGF), and heme oxygenase 1 (HO-1). Up-regulation of HIF-1alpha and HIF-regulated genes was also verified by Western blotting analysis. To elucidate responsible mechanisms of cobalt in the amelioration of tubuloniterstitial injury, terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) staining was conducted at 5 weeks. A combination therapy with angiotensin receptor blocker (ARB), olmesartan, was also challenged.. Although the intervention did not change glomerular structural damage or urinary protein excretion rate, tubulointerstitial injury was improved in cobalt-treated animals when compared with the vehicle-treated group. The amelioration was associated with the parallel up-regulation of renoprotective, HIF-regulated gene expression. TUNEL staining revealed that the number of apoptotic cells was reduced in the cortex by cobalt administration, suggesting that renoprotection was achieved partly through its antiapoptotic properties. Furthermore, it was demonstrated that cobalt treatment exerts additional renoprotective effects with the ARB treatment in this model.. Maneuvers to activate HIF in the ischemic tubulointerstitium will be a new direction to future therapeutic strategies.

Topics: Animals; Antibodies; Antimutagenic Agents; Apoptosis; Capillaries; Cobalt; Erythropoietin; Gene Expression Regulation; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Heme Oxygenase-1; Hypoxia; Hypoxia-Inducible Factor 1; In Situ Nick-End Labeling; Isoantibodies; Kidney Tubules; Male; Nephrectomy; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Reperfusion Injury; Vascular Endothelial Growth Factor A

The ICR-derived glomerulonephritis (ICGN) mouse, a new inbred mouse strain with a hereditary nephrotic syndrome, is considered to be a good model of human idiopathic nephrotic syndrome and notably exhibits proteinuria and hypoproteinemia from the neonatal stage. In chronic renal disorder (CRD), anemia is a major subsequent symptom (renal anemia). The precise cause of renal anemia remains unclear, primarily owing to the lack of appropriate spontaneous animal models for CRD. To establish adequate animal models for anemia with CRD, we examined the hematological-biochemical properties and histopathological characteristics. With the deterioration of renal function, ICGN mice developed a normochromic and normocytic anemia, and exhibited normochromic and microcytic at the terminal stage. The expression of erythropoietin (EPO) mRNA both in the kidneys and liver and the EPO leak into the urine were observed in ICGN mice, indicating a disrupted metabolism of EPO in ICGN mice. In addition, a lack of iron induced by the hemolysis in the spleen and the leak of transferrin into urine as proteinuria aggravated the anemic condition. In conclusion, the ICGN mouse is a good model for anemia with CRD.

Topics: Analysis of Variance; Anemia; Animals; Crosses, Genetic; Disease Models, Animal; Erythropoietin; Glomerulonephritis; Hematologic Tests; Histological Techniques; Kidney; Kidney Failure, Chronic; Liver; Mice; Mice, Inbred ICR; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Although the presence of anaemia after renal transplantation is well known, specific data on the prevalence and risk factors are scarce. Results from the recent TRansplant European Survey on Anemia Management (TRESAM) survey, conducted in 4263 recipients of a renal transplant from 72 centres in Europe, revealed that 38.6% of patients were anaemic [haemoglobin (Hb) concentrations < or =13 g/dl for male patients and < or =12 g/dl for female patients]. Of these patients, 11.6% had moderate anaemia (Hb concentrations >11 and < or =12 g/dl for male patients and >10 and < or =11 g/dl for female patients), while 8.5% had severe anaemia (Hb concentrations < or =11 g/dl for male patients and < or =10 g/dl for female patients). A strong association existed between Hb concentration and renal graft function. Of the patients with a serum creatinine level >2 mg/dl (which indicates impaired kidney function), 60.1% were anaemic, compared with 29.0% of those with a serum creatinine level < or =2 mg/dl (P<0.01). Other risk factors for anaemia include therapy with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, the use of azathioprine or mycophenolate mofetil, kidneys from older donors and recent infections. Furthermore, only 18.8% of patients with severe anaemia were treated with erythropoietic therapy. The findings from the TRESAM survey are in agreement with the results from another recently published study that included 128 renal transplant patients from two centres in the USA, who were followed for 5 years after transplantation. It was found that 30% of patients were anaemic at some point after transplantation. The prevalence increased with time after transplantation, with 26% of patients being anaemic 5 years' post-transplant. A multivariate logistic regression model identified three risk factors for post-transplant anaemia: serum total CO(2), blood urea nitrogen and creatinine. There is an unexpectedly high incidence of anaemia in patients with a functioning renal transplant: around one-third of these patients are anaemic. Most of the evidence suggests that impaired erythropoietin production by the renal allograft is the most important pathogenic factor of post-transplant anaemia. Whether this high incidence of anaemia may be an additional cardiovascular risk factor in renal transplant patients remains to be proven. However, there does not appear to be any reason why anaemic renal transplant recipients should not be treated like any o

Topics: Anemia; Creatinine; Erythropoietin; Glomerulonephritis; Humans; Incidence; Kidney Transplantation; Logistic Models; Postoperative Period; Risk Factors; Transplantation, Homologous

The ICR-derived glomerulonephritis (ICGN) mouse, a novel inbred mouse strain with a hereditary nephrotic syndrome, develops severe anemia associated with chronic renal failure. To reveal the pathogenic mechanism of anemia in ICGN mice, we subcutaneously administered recombinant human erythropoietin (rhEPO; 5 IU/mouse/day) or saline for 5 days to ICGN mice. In terminal-stage ICGN mice with severe anemia, rhEPO significantly increased hematocrit (Ht), red blood cells (RBC) and hemoglobin levels. Endogenous EPO levels in peripheral blood were reduced by rhEPO injection. No histopathological changes in bone marrow and kidneys were induced by rhEPO injection. Insufficiency of EPO may cause anemia in ICGN mice.

Topics: Anemia; Animals; Bone Marrow; Disease Models, Animal; Erythrocyte Count; Erythropoietin; Female; Glomerulonephritis; Hematocrit; Hemoglobins; Injections, Subcutaneous; Kidney; Kidney Failure, Chronic; Male; Mice; Mice, Inbred ICR; Recombinant Proteins

Topics: Adolescent; Animals; Biomarkers; Child; Erythropoietin; Female; Gene Expression; Glomerulonephritis; Humans; Immunohistochemistry; In Situ Hybridization; Kidney Glomerulus; Male; Mice; Mice, Inbred ICR; Receptors, Erythropoietin; RNA, Messenger

One of the complications of hemodialysis (HD) therapy is anemia caused by erythropoietin (EPO) deficiency. Recombinant EPO (rEPO) has been used routinely as a supplemental treatment. Erythrocyte expression of the complement regulatory proteins decay accelerating factor (DAF) and CD59 restricts complement activation and inhibits hemolysis. We hypothesized that the efficacy of rEPO treatment may be caused in part by the ability of rEPO to increase erythrocyte expression of DAF and CD59.. DAF, CD59, and complement receptor 1 (CR1) levels were analyzed for a group of 95 HD patients and compared with those of a control group. To evaluate effects of discontinuation of rEPO therapy, rEPO therapy was stopped for 12 HD patients until hematocrits decreased to less than 25%. DAF and CD59 levels then were reanalyzed.. In the 95 HD patients, three factors correlated significantly: DAF and CD59 (r = 0.642), DAF and CR1 (r = 0.503), and CD59 and CR1 (r = 0.324), whereas no correlations were found in the group of 42 healthy controls. In the experiment in which rEPO therapy was discontinued, 8 of 12 patients reached the defined level of anemia 4 to 7 weeks after rEPO treatment had been withheld. Both DAF and CD59 levels decreased significantly after discontinuation of rEPO therapy (P < 0.01). DAF and CD59 levels increased in all 8 patients after rEPO treatment was reinitiated (P < 0.01), and CR1 levels increased in 5 of 8 patients. Four of 12 patients showed no evidence of anemia after discontinuation of rEPO treatment. In these patients, DAF, CD59, and CR1 levels did not change before or after withholding rEPO therapy.. One of the mechanisms mediating the efficacy of EPO therapy is increased DAF and CD59 expression.

Topics: Anemia; CD55 Antigens; CD59 Antigens; Chronic Disease; Complement C3; Diabetes Mellitus; Erythrocytes; Erythropoietin; Glomerulonephritis; Humans; Middle Aged; Receptors, Complement; Recombinant Proteins; Renal Dialysis; Renal Insufficiency

The mean arterial pressure (MAP) usually serves as an expression of blood pressure in patients on chronic haemodialysis (PCHD), instead of using solely systolic or diastolic pressure. Pulse pressure (PP) has been recognized as an important correlate of mortality in PCHD. We conducted this study in order to demonstrate clinical and biochemical determinants and variability of predialysis and postdialysis MAP and PP values. A total of 136 single haemodialysis (HD) treatments in 23 subjects (PCHD, 11 male and 12 female patients) were processed during 15 months. MAP before HD was in negative correlation with haemoglobin (P<0.001) and body mass index (BMI) (P<0.001), and in positive correlation with weekly erythropoietin dosage (P=0.017). MAP after HD was in negative correlation with haemoglobin (P<0.001), ultrafiltration per HD (P=0.015), and BMI (P=0.001), and in positive correlation with weekly erythropoietin dosage (P=0.003). PP before HD was in negative correlation with parathyroid hormone (PTH) level (P=0.020), haemoglobin (P<0.001), ultrafiltration per HD (P=0.001), and years on the chronic HD treatment (P=0.001), and in positive correlation with weekly erythropoietin dosage (P<0.001) and age (P<0.001). PP after HD was in significant negative correlation with PTH (P=0.015), haemoglobin (P=0.005), ultrafiltration per HD (P<0.001), BMI (P=0.003), and in positive correlation with weekly erythropoietin dosage (P<0.001) and age (P=0.004). Multiple regression analyses unveiled the strongest and negative correlations between MAP before HD and BMI (beta=-0.37, P=0.01); MAP after HD and haemoglobin (beta=-0.36, P=0.01); PP after HD and ultrafiltration/body weight ratio (beta=-0.41, P<0.001). The strongest and positive correlation was found between PP before HD and erythropoietin dosage per week (beta=0.51, P&<0.001). In conclusion, our findings support the assumption that PP and MAP are associated with different clinical parameters. PP values have advantages as the method of blood pressure expression.

Topics: Alkaline Phosphatase; Biomarkers; Blood Pressure; Blood Proteins; Body Mass Index; Cholesterol, HDL; Chronic Disease; Diabetic Nephropathies; Erythropoietin; Female; Glomerulonephritis; Humans; Male; Phosphorus; Pyelonephritis; Regression Analysis; Renal Dialysis; Sex Factors; Statistics as Topic; Time Factors; Treatment Outcome; Ultrafiltration

Topics: Adult; Anemia; Erythropoietin; Female; Glomerulonephritis; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Platelet Count; Recombinant Proteins; Renal Dialysis; Thrombopoietin

Management of renal anemia in pregnancy remains a major issue. We report the use of human recombinant erythropoietin (rhEPO) combined with parenteral iron sucrose in a pregnancy with chronic glomerulonephritis, progressive anemia and initially normal blood pressure. Therapy from 32 weeks gestation increased the hematocrit by 0.4% daily and the hemoglobin from 8.6 to 10.3 g/dL within 2 weeks. Despite the improvement of anemia, Cesarean section had to be performed at 34 weeks due to acute hypertension, preeclampsia and worsening renal function. Blood pressure remained elevated postpartum. Because of symptomatic postpartum anemia with a hemoglobin of 7.5 g/dL on the 5th postoperative day rhEPO in combination with parenteral iron sucrose was readministered over 3 following days. Blood pressure reached a maximum of 210/130 mm Hg 3 weeks later. Possible causes include advancing preeclampsia and renal disease, but also rhEPO (due to its intrinsic vascular effects and/or the rapid response of the hematocrit), and a combination of both.

Topics: Adult; Anemia; Erythropoietin; Female; Glomerulonephritis; Humans; Pre-Eclampsia; Pregnancy; Puerperal Disorders; Recombinant Proteins

Recombinant human erythropoietin (rHuEpo) may affect the human immune system. The aim of the study was to examine changes in CD4(+) and CD8(+) T-cell subpopulations, the expression of the inhibitory molecule, CD152 on T lymphocytes and the levels of interleukins (IL) 2, 6, 10, 12 and tumour necrosis factor alpha (TNF alpha) in primary glomerulonephritis chronic haemodialysis (HD) patients before and under rHuEpo treatment.. Expression of T-cell surface molecules was measured in 14 HD patients ex vivo by flow cytometry of lymphocytes sampled from peripheral blood and in vitro using whole blood cell cultures stimulated either with phytohaemagglutinin (PHA) or with physiological as well as non-physiological doses of rHuEpo. The concentrations of the cytokines were measured in the supernatants from non- or PHA-stimulated cultures using bioassays (IL2, IL6, TNF alpha) or ELISA tests (IL10, IL12).. Compared with findings before the start of rHuEpo therapy the CD4(+)/CD8(+) ratio increased after 1 year of follow-up, whereas the percentage of CD152(+) peripheral blood lymphocytes decreased. The increase of the CD4(+)/CD8(+) ratio was dependent on a decrease of the percentage of CD8(+) cells. The decrease of CD152(+) population affected mainly CD8(+)CD152(+) cells. All these effects became apparent after 6 months of rHuEpo treatment. In vitro stimulation of whole blood cultures revealed that the addition of PHA up-regulated the percentage of CD152(+) lymphocytes, while physiological concentrations of rHuEpo decreased the percentage of CD8(+)152(+) T cells. None of the stimuli used affected the percentage of CD8(+) T cells. The pattern of the cytokines shifted toward TH1 phenotype (increase of IL2 and 12 levels) with a decreased level of proinflammatory cytokines (decrease of IL6 and TNFalpha levels).. The observed decrease of CD152(+) lymphocytes together with the decrease of CD8(+) cells may reflect the improved immune response observed in HD patients under rHuEpo treatment.

Topics: Abatacept; Anemia; Antigens, CD; Antigens, Differentiation; CD4-CD8 Ratio; CTLA-4 Antigen; Cytokines; Epoetin Alfa; Erythropoietin; Ferritins; Glomerulonephritis; Hematinics; Humans; Immunoconjugates; Lymphocyte Count; Lymphocytes; Middle Aged; Recombinant Proteins; Renal Dialysis; Time Factors; Transferrin

Erythropoietin, a glycoprotein growth hormone that is produced primarily in the kidneys, promotes mitosis and survival of erythroid progenitors. The recent synthesis of the human form of the hormone by recombinant technology has provided a new therapeutic option, which is being used in both human and veterinary medicine for treatment of various anemias. A mature male rough-toothed dolphin, Steno bredanensis, was treated with human recombinant erythropoietin in an attempt to resolve a nonregenerative anemia. Two i.m. injections 48 hr apart were associated with an almost immediate increase in circulating immature reticulocytes, total reticulocytes, and nucleated erythrocytes. Over the next several weeks, the hematocrit, hemoglobin, and erythrocyte counts returned to normal, and the animal was subsequently released back into the wild. Endogenous erythropoietin concentrations were determined for this animal as well as three other conspecifics by an enzyme-linked immunosorbent assay for human erythropoietin. These measurements showed circulating erythropoietin concentrations (5-20+ mU/ml) similar to those of most other mammals. This study suggests that human recombinant erythropoietin can be safely and effectively used in this species and may have applicability to other cetacean species for the treatment of nonregenerative anemia. Caution should be exercised during long-term use because production of antibodies to human recombinant and endogenous erythropoietin may lead to potentially serious side effects.

Topics: Anemia; Animals; Anti-Bacterial Agents; Anti-Ulcer Agents; Dolphins; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Flow Cytometry; Gentamicins; Glomerulonephritis; Hematocrit; Hematuria; Hemoglobins; Male; Proteinuria; Ranitidine; Recombinant Proteins; Reference Values; Sucralfate

Topics: Abdominal Pain; Adult; Analgesics, Non-Narcotic; Anemia, Iron-Deficiency; Appendicitis; Epoetin Alfa; Erythropoietin; Fever; Gastrointestinal Hemorrhage; Glomerulonephritis; Hematinics; Humans; Hypertension; Ibuprofen; Kidney Failure, Chronic; Male; Nursing Diagnosis; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Recombinant Proteins; Renal Dialysis

Topics: Aged; Erythropoietin; Female; Glomerulonephritis; Hemochromatosis; Hemoglobins; Humans; Kidney Failure, Chronic; Kidney Transplantation; Recombinant Proteins; Transferrin

In 1980, the first Moroccan hemodialysis center was founded in Casablanca. The number of centers has been increasing since then, to reach 61 centers to wards the of 1996. There are 1800 hemodialysed (males 59%, females 41%) with and average age of 51 +/- 4 years. In about one third of the cases, the cause of the end stage renal failure remains unknown. However, chronic glomerulonephritis comes at the head of known causes (25%), followed by interstitial nephritis (19%). A temporary vascular access (catheter) was necessary in 81% of cases when dialysis has started in emergency in 61% of patients. Infections were the most frequent complications (21%) namely septicaemia (8%) and tuberculosis (7%). The vaccination against hepatitis B virus is done systematically in all the centers, and the number of chronic carriers of HBS Ag is about 7%. Further more, serological C virus is positive in 40% of the hemodialysed patients. Cardio-vascular complications were dominated by percarditis (13%) especially at the beginning of the dialysis. Anaemia remains very frequent and often very important requiring multiple blood transfusions (35%) in the absence of erythropoietin treatment. The death rate, which is very difficult to estimate, is of about 18%. Peritoneal dialysis was used in 50 patients but only four patient continued on peritoneal dialysis therapy. 108 patients were transplanted (23 cases in Morocco, 85 in other countries) with a waiting list of 0 to 12 years. Hemodialysed Moroccan's population is characterised by the high number of unknown causes and the gravity of the admission stage. A renal effort in prophylactic should be performed to avoid certain causes of renal failure.

Topics: Adolescent; Adult; Aged; Ambulatory Care Facilities; Anemia; Cardiovascular Diseases; Carrier State; Catheters, Indwelling; Child; Child, Preschool; Comorbidity; Erythropoietin; Female; Glomerulonephritis; Hepatitis, Viral, Human; Humans; Infant; Infections; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Morocco; Nephritis, Interstitial; Peritoneal Dialysis; Renal Dialysis; Transfusion Reaction; Vaccination

Adrenomedullin (AM), a novel vasodilator peptide, is produced by C-terminal amidation reaction of AM-glycine. AM-glycine, an intermediate form of AM (iAM), is processed from pro AM. AM circulating in the human blood stream was found to consist of an amidated mature form (mAM) and iAM. Biological activity is exerted only by mAM.. To investigate the pathophysiological role of mAM in renal disease, we measured plasma concentrations of mAM as well as total AM (tAM), representing both mAM and iAM, in patients with various renal diseases. In addition, plasma ANP level was measured in all patients.. The concentrations of plasma mAM in renal failure with dialysis (2.1 +/- 0.2 fmol/ml, mean +/- SEM) and without dialysis (1.2 +/- 0.2) were significantly (p < 0.05) higher than those in control group (0.5 +/- 0.1). However, the plasma ANP level was increased only in renal failure patients with dialysis. Plasma mAM levels were significantly correlated positively with serum creatinine levels and negatively with hematocrit. No significant difference was noted in the ratio of mAM/tAM between renal failure patients and healthy subjects.. These results suggest that plasma mAM is increased in renal failure in relation to deterioration of renal function, while the amidation process of AM seems to be unaffected in patients with renal failure.

Topics: Adrenomedullin; Adult; Aged; Atrial Natriuretic Factor; Calcitonin Gene-Related Peptide; Creatinine; Erythropoietin; Female; Glomerulonephritis; Glycine; Hematocrit; Humans; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Peptides; Prodrugs; Recombinant Proteins; Renal Dialysis; Vasodilator Agents

The impairment of function of human T lymphocytes, leading to an inappropriate cytokine production, is partially responsible for defective immunological response in hemodialysis patients (HD). Recent data suggest that recombinant human erythropoietin (rhEPO) may exert immunological effects. The aim of this study was to find out whether rhEPO treatment of the HD patients may have an effect on the interleukin 2 (IL-2) production by their whole blood cell cultures. The study was carried out in 10 HD patients receiving rhEPO for 6 months. Compared with the levels seen before the treatment, the concentration of IL-2 increased in the phytohemagglutinin-stimulated whole blood cell cultures of 7 of 10 patients under study. Addition of rhEPO in vitro to the whole blood cell cultures of the HD patients before implementation of erythropoietin confirmed that rhEPO is able to directly stimulate IL-2 production. Our studies show that the therapy with rhEPO affects IL-2 secretion.

Topics: Adjuvants, Immunologic; Adult; Blood Cells; Cells, Cultured; Chromogenic Compounds; Chronic Disease; Colorimetry; Coloring Agents; Erythropoietin; Female; Glomerulonephritis; Humans; Interleukin-2; Leukocyte Count; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Recombinant Proteins; Renal Dialysis; T-Lymphocytes; Tetrazolium Salts; Thiazoles

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

Topics: Adolescent; Anemia, Aplastic; Delayed-Action Preparations; Erythropoietin; Ferrous Compounds; Glomerulonephritis; Humans; Kidney Failure, Chronic; Male; Parvoviridae Infections; Parvovirus B19, Human; Renal Dialysis; Uremia

Topics: Beverages; Chronic Disease; Erythropoietin; Female; Follow-Up Studies; Glomerulonephritis; Humans; Middle Aged; Polycythemia; Renal Dialysis; Vegetables

Recombinant human erythropoietin (rHUEPO) was produced by Chinese hamster ovary cells and commercially distributed to hospitals by two pharmaceutical companies in Japan ('ESPO' by Kirin Brewery Co. Ltd., and Sankyo Co. Ltd., and 'EPOGIN' by Chugai Pharmaceutical Co. Ltd.) These products contained about 1% N-glycolylneuraminic acid (Neu5Gc) in total sialic acid content. Since humans do not synthesize Neu5Gc, successive injection of Neu5Gc-containing products was feared to lead to allergic-like symptoms. Therefore, serum levels of antibodies of Neu5Gc epitope in 90 patients who received repeated i.v. injections of ESPO or EPOGIN were determined by an enzyme immunoassay using Neu5Gc alpha 2-3Gal beta 1-4Glc-Cer, GM3(Neu5Gc), as an antigen and compared with those in 100 healthy persons. Either no or low antibody levels were detected in both groups with no significant difference. In 40 patients who received s.c. injections of ESPO or EPOGIN, serum HD antibody levels were determined before and after weekly therapeutic injections carried out for one to several months, but no significant elevations were detected in all patients. The above results indicated that therapeutic administration of rHuEPO to patients to patients with chronic renal failure is safe from allergic-like side effects associated with the production of Neu5Gc-specific antibodies, and it was concluded that Neu5Gc epitope of rHuEPO is minimally antigenic in humans.

Topics: Adolescent; Adult; Aged; Animals; Antibodies, Heterophile; CHO Cells; Cricetinae; Epitopes; Erythropoietin; Glomerulonephritis; Humans; Immunoenzyme Techniques; Middle Aged; Neuraminic Acids; Recombinant Proteins

Topics: Child, Preschool; Erythropoietin; Female; Glomerulonephritis; Glycated Hemoglobin; Humans; Recombinant Proteins

Topics: Adult; Anemia; Erythropoietin; Female; Glomerulonephritis; Humans; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic

Topics: Amputation, Surgical; Bloodletting; Cadaver; Erythropoietin; Glomerulonephritis; Hematocrit; Humans; Hypertension, Renal; Ischemia; Kidney Transplantation; Leg; Male; Middle Aged; Polycythemia; Postoperative Complications; Renal Dialysis

The dialysis adequacy was considered as the treatment method which eradicated the symptoms and signs of uremia and led to the full rehabilitation of treated patients. The chronic renal failure patients substitutional treatment using both peritoneal dialysis and hemodialysis assures correction of biochemical disturbances but only 33% of dialyzed patients are fully rehabilitated. Such situation is caused by the uremic anemia. The erythropoietin deficit is the main reason of the uremic anemia. The clinical effects of the erythropoietin treatment in hemodialyzed, peritoneal dialyzed and pre-dialyzed patients were proved. The erythrocytes increment to the normal or almost normal levels may caused the dialysis kinetics changes. During the r-Hu EPO treatment in both hemodialyzed and peritoneal dialyzed patients the dialysis effectiveness changes occurred. The dialysis therapy adequacy is mainly caused by the dialysis efficiency and additionally by the residual renal function and metabolism state. Taking into account own peritoneal dialysis kinetics parameters research results during the r-Hu EPO treatment the dialysis adequacy was evaluated. The aim of this study was the optimal dialysis scheme definition when the peritoneal transfer changes occurred as the r-Hu EPO treatment effect.

Topics: Adult; Erythropoietin; Female; Glomerulonephritis; Hematocrit; Hemoglobins; Humans; Kidney Diseases; Male; Middle Aged; Peritoneal Dialysis; Recombinant Proteins

Thyroid function has been assessed in 36 clinically euthyroid patients undergoing regular haemodialysis. The influence of erythropoietin administration on the thyroid function tests has been determined. Thyroid-stimulating hormone (TSH) has been found to be elevated in 8% of the patients. Free tri-iodothyronine was below the normal range in 67% of the population. Free thyroxine (FT4) was low in 67% of the patients when tested by an analogue method. FT4 tested by a 2-stage method in a subgroup of 22 patients was abnormally low in only 23% of the patients. Erythropoietin did not seem to improve these thyroid abnormalities despite a partial correction of the anaemia. A rise in FT4 was also observed after haemodialysis without a concomitant change in TSH concentration. This FT4 elevation was attributed to the effect of heparin.

Topics: Adult; Aged; Erythropoietin; Female; Glomerulonephritis; Humans; Injections, Subcutaneous; Male; Middle Aged; Nephritis, Interstitial; Radioimmunoassay; Renal Dialysis; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Topics: Adult; Aged; Erythropoiesis; Erythropoietin; Female; Glomerular Filtration Rate; Glomerulonephritis; Hemoglobinometry; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Nephritis, Interstitial; Polycystic Kidney Diseases

The effect of recombinant human erythropoietin (rHuEPO) on the lymphocyte subpopulations of maintenance hemodialysis patients has been studied. Peripheral lymphocyte counts, lymphocyte subpopulations (Two color analysis) and PHA-induced proliferative response were measured before and after rHuEPO administration during 8 months in 22 stable hemodialysis patients (mean age 52 years, mean duration of dialysis 48 months). We could find a significant increase in the proportions of CD4+ Leu8- cells, HLA-DR+ cells, CD8+ HLA-DR+ cells, CD14+ HLA-DR+ cells and CD4+ Leu8-/CD8+ CD11b+ cells ratios after rHuEPO therapy. In addition, a significant decrease in the proportions of CD16+ CD57- cells and CD20+ cells could be found after rHuEPO therapy. These results suggest that rHuEPO administration to stable hemodialysis patients induces increases in lymphocytes categorized into helper subset groups and in activated T lymphocytes.

Topics: Adult; Aged; Antigens, CD; Chronic Disease; Erythropoietin; Female; Glomerulonephritis; Humans; Lymphocyte Activation; Lymphocyte Subsets; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Topics: Adult; Anemia; Autonomic Nervous System; Blood Pressure; Dopamine beta-Hydroxylase; Erythropoietin; Female; Glomerulonephritis; Humans; Male; Middle Aged; Nephritis; Norepinephrine; Pre-Eclampsia; Pregnancy; Recombinant Proteins; Renal Dialysis

Six patients with acute renal failure, in five cases due to acute crescentic glomerulonephritis and in one case due to total bilateral renal cortical necrosis, were studied. All had serum erythropoietin (EPO) concentrations in the normal range, despite a relatively severe anaemia. Half-life and plasma clearance of intravenously injected recombinant human erythropoietin (rhEPO) were determined. The results indicate that the lack of compensatory increase in serum EPO to the anaemic stimulus is not due to increased catabolism, but to decreased synthesis of the renal hormone. Two patients were treated with rhEPO (Eprex). In marked contrast to untreated controls, both patients responded with vigorous reticulocytosis and normalization of haemoglobin levels while they were still in severe renal failure. These results are similar to our previous findings in patients with acute renal failure due to tubular necrosis. Under all three conditions the defective EPO synthesis is probably the dominant pathogenetic factor for the largely aregeneratory anaemia of prolonged cases, and for the sluggish restoration of red cell mass during recovery of renal function. It is concluded that defective synthesis of EPO is not only a permanent and irreversible feature of severe chronic renal failure, but that it is also present, usually in a transient and reversible form, in different types of acute renal failure.

Topics: Acute Disease; Aged; Erythropoietin; Female; Glomerulonephritis; Hemoglobins; Humans; Kidney Cortex Necrosis; Leukocyte Count; Male; Middle Aged; Recombinant Proteins; Reticulocytes

We have investigated anemia in patients at different stages of the evolution of three chronic renal diseases: Balkan endemic nephropathy (BEN), chronic pyelonephritis (PN) and chronic glomerulonephritis (GN). A total of 88 patients with creatinine clearances from 9 to 118 ml/min and hemoglobin concentrations from 70 to 160 g/l were studied with regard to the relationship, if any, between erythropoietin production and the type and stage of nephropathy. Anemia in BEN was a particular focus of interest since it had been stated that in BEN, anemia precedes renal failure. Our data neither prove nor disprove this statement. A significant positive correlation between creatinine clearance and hemoglobin concentration was found in all three nephropathies, indicating that in the patients studied the severity of anemia increased with the impairment of renal function regardless of the underlying disease. Serum levels of immunoreactive erythropoietin were in the normal range in 54 patients, moderately increased in 20 and slightly decreased in 14. The erythropoietin level appears to be unrelated to the stage of renal failure or the type of nephropathy. The only exception was the subgroup where the patients with glomerulonephritis and normal renal function had increased serum erythropoietin levels and significantly higher parameters of red blood cell concentration than the patients from the same subgroup with tubulointerstitial nephropathies. In patients with severe renal failure and anemia, serum erythropoietin levels were inappropriately low for the degree of anemia, indicating that erythropoietin plays a role in the pathogenesis of the anemia.

Topics: Adult; Aged; Anemia; Balkan Nephropathy; Creatinine; Erythropoietin; Female; Glomerulonephritis; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Nephritis, Interstitial; Pyelonephritis

Topics: Adult; Blood Pressure; Erythropoietin; Glomerulonephritis; Humans; Male; Middle Aged; Nephrectomy; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins; Renal Dialysis; Seizures; Transfusion Reaction

Topics: Blood Proteins; Child; Erythropoiesis; Erythropoietin; Glomerulonephritis; Humans; Pyelonephritis

Erythrocytosis was seen in two men during maintenance hemodialysis therapy for end-stage renal disease secondary to apparent chronic glomerulonephritis. Nonrenal causes of erythrocytosis such as polycythemia vera, chronic hypoxemia, high-oxygen affinity hemoglobin, and hepatoma were excluded by appropriate clinical studies. A computed tomographic scan of the abdomen showed numerous renal cysts in each patient consistent with acquired cystic disease of end-stage kidneys. Peripheral serum erythropoietin levels were elevated as measured by sensitive radioimmunoassay. The findings suggest that the erythrocytosis is caused by an erythropoietic mechanism related to the diseased kidneys. A review of the literature failed to show previous reports of this clinical association.

Topics: Erythropoietin; Glomerulonephritis; Hematocrit; Humans; Kidney Diseases, Cystic; Male; Middle Aged; Polycythemia; Renal Dialysis; Time Factors

An exceptionally high serum erythropoietin (EPO) activity was documented in an anephric patient with severe anemia who required transfusions every 4 weeks. The patient's serum EPO was comparable to normal human urinary EPO in the polycythemic mouse assay and was neutralized by an antiserum against EPO. The patient's serum inhibited EPO stimulated-heme synthesis by normal human marrow cells in vitro. This finding suggests that an inhibitor played an important role in causing the anemia of this uremic patient.

Topics: Adolescent; Anemia; Bone Marrow; Cells, Cultured; Erythropoietin; Female; Glomerulonephritis; Humans; Nephrectomy; Renal Dialysis

Topics: Adult; Blood Transfusion; Erythropoiesis; Erythropoietin; Glomerulonephritis; Hematocrit; Humans; Kidney Transplantation; Male; Transplantation, Homologous

Topics: Chronic Disease; Erythropoietin; Glomerulonephritis; Humans; Kidney Failure, Chronic; Leukocyte Count; Pyelonephritis; Renal Dialysis; Reticulocytes

Topics: Adolescent; Adult; Angiotensin II; Antigen-Antibody Reactions; Antigens; Erythropoietin; Female; Glomerulonephritis; Hematocrit; Humans; Iron Radioisotopes; Kidney Failure, Chronic; Male; Methods; Middle Aged; Nephrectomy; Pyelonephritis; Radioimmunoassay; Renal Dialysis; Renin

Topics: Adult; Chronic Disease; Erythrocyte Count; Erythropoiesis; Erythropoietin; Female; Glomerulonephritis; Hemoglobins; Humans; Infusions, Parenteral; Kidney Diseases, Cystic; Kidney Failure, Chronic; Male; Middle Aged; Plasmapheresis; Pyelonephritis; Reticulocytes

Topics: Acute Disease; Child; Chronic Disease; Erythropoietin; Glomerulonephritis; Humans

Topics: Adult; Animals; Blood Transfusion; Chronic Disease; Creatinine; Erythrocyte Count; Erythropoietin; Female; Glomerulonephritis; Hemoglobins; Humans; Iron; Iron Isotopes; Male; Mice; Mice, Inbred Strains; Middle Aged; Renal Dialysis; Reticulocytes; Time Factors

Topics: Animals; Citrates; Ducks; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Glomerulonephritis; Immune Sera; Iron Isotopes; Kidney; Male; Mice; Nephrectomy; Polycythemia; Rabbits

Topics: Anemia, Aplastic; Animals; Ascites; Blood Transfusion; Chronic Disease; Erythropoietin; Female; Glomerulonephritis; Humans; Hydronephrosis; Immune Sera; Iron Isotopes; Kidney Diseases; Kidney Failure, Chronic; Male; Mice; Phenacetin; Pyelonephritis; Renal Dialysis; Uremia

Topics: Adult; Animals; Biological Assay; Blood Urea Nitrogen; Child; Creatinine; Erythropoiesis; Erythropoietin; Glomerulonephritis; Hematocrit; Humans; Iron Isotopes; Kidney Neoplasms; Kidney Transplantation; Male; Mice; Middle Aged; Nephrectomy; Renal Dialysis; Reticulocytes; Testosterone; Transplantation, Homologous

Topics: Adult; Blood Pressure; Creatinine; Erythrocyte Count; Erythropoiesis; Erythropoietin; Female; Glomerulonephritis; Hematocrit; Hemoglobinometry; Humans; Hypertension; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Nephritis, Interstitial; Phenolphthaleins; Urea

Topics: Adolescent; Child; Erythropoietin; Female; Glomerulonephritis; Humans; Iron Isotopes; Kidney; Kidney Transplantation; Male; Middle Aged; Nephrectomy; Transplantation, Homologous

Topics: Blood Transfusion; Bone Marrow Examination; Child; Erythropoietin; Glomerulonephritis; Histocompatibility; Humans; Iron Isotopes; Kidney Transplantation; Male; Nephrectomy; Transplantation Immunology

Topics: Adult; Anemia; Biological Assay; Centrifugation; Electrophoresis; Erythropoietin; Female; Glomerulonephritis; Humans; Infant; Iron Isotopes; Kidney; Male; Plasma; Solubility; Tissue Extracts; Uremia

In 123 patients with arterial hypertension the haemoglobin values were determined before and during long-term antihypertensive drug treatment. The haemoglobin values found before treatment did not differ from those found in the normal population. In both sexes the haemoglobin values showed a significant increase after prolonged treatment. In males the average values rose from 15.1 to 16.7 g./100 ml., and in females from 13.96 to 14.82 g./100 ml. The increase in the haemoglobin concentration does not seem to be clearly correlated to the duration of treatment or to the decrease produced in mean blood pressure. On the other hand, the increase in haemoglobin depended to some extent on the nature of treatment. Diuretics alone resulted in a moderate increase only, whereas diuretics in combination with other antihypertensive drugs produced a more pronounced increase in haemoglobin values.

Topics: Adult; Aged; Antihypertensive Agents; Creatinine; Diuretics; Erythropoietin; Female; Glomerulonephritis; Hematocrit; Hemoglobinometry; Humans; Hydrochlorothiazide; Male; Methyldopa; Middle Aged; Polycythemia; Polythiazide; Pyelonephritis; Renal Artery Obstruction; Triamterene

Topics: Adult; Aged; Autoradiography; Cobalt; Cobalt Isotopes; Erythropoiesis; Erythropoietin; Female; Glomerulonephritis; Humans; Kidney; Kidney Function Tests; Liver; Male; Middle Aged

Topics: Adolescent; Adult; Blood Platelets; Erythropoiesis; Erythropoietin; Female; Glomerulonephritis; Hematocrit; Humans; Kidney Transplantation; Male; Reticulocytes; Transplantation, Homologous

Topics: Absorption; Anemia, Hypochromic; Erythropoietin; Glomerulonephritis; Humans; Iron; Uremia

Topics: Blood Platelets; Blood Urea Nitrogen; Bone Marrow Examination; Epoetin Alfa; Erythropoiesis; Erythropoietin; Glomerulonephritis; Hematocrit; Hemoglobinometry; Humans; Hypoxia; Iron; Iron Isotopes; Kidney; Kidneys, Artificial; Leukocyte Count; Male; Nephrectomy; Physiology; Pyelonephritis; Radioisotopes; Radionuclide Imaging; Reticulocytes; Uremia