losartan-potassium and Cat-Diseases

It is estimated that 15-30% of geriatric cats will develop chronic kidney disease (CKD), and that 30-65% of these cats will develop anemia as their renal disease worsens. Anemia of renal disease is multifactorial in its pathogenesis, but the main cause is reduced production of erythropoietin, a renal hormone that controls the bone marrow's production of red blood cells, as kidney disease progresses.. It is important to recognize the presence of anemia of renal disease so that adequate treatment may be instituted to improve quality of life and metabolic function. Erythrocyte-stimulating agents (ESAs), such as epoetin alfa, epoetin beta and darbepoetin alfa, have been developed to counteract the effects of decreased erythropoietin production by the kidneys. These treatments, which are the focus of this review, have 83% similarity in amino acid sequence to the feline hormone. On average, the target packed cell volume (>25%) is reached within 3-4 weeks of ESA therapy.. The use of ESAs has been associated with a number of complications, such as iron deficiency, hypertension, arthralgia, fever, seizures, polycythemia and pure red cell aplasia (PRCA). Darbepoetin has a prolonged half-life compared with epoetin and thus can be given only once a week, instead of three times a week. The incidence of PRCA appears to be decreased with darbepoetin use when compared with epoetin use in cats.. There is limited published evidence to date to underpin the use of ESAs in cats. This review draws on the relevant publications that currently exist, and the authors' personal experience of using these therapies for over 5 years.

Topics: Anemia; Animals; Cat Diseases; Cats; Darbepoetin alfa; Diagnosis, Differential; Drug Administration Schedule; Erythropoietin; Hematinics; Kidney Failure, Chronic; Male; Recombinant Proteins

Topics: Animals; Cat Diseases; Cats; Congresses as Topic; Diet, Protein-Restricted; Dietary Supplements; Erythropoietin; Recombinant Proteins; Uremia

EPO is a hematopoietic growth factor produced in the kidney that stimulates erythropoiesis. It effectively treats hypoproliferative anemia associated with CRF, improving quality of life in these patients. Other uses that are poorly characterized in veterinary medicine include treatment of cancer patients on chemotherapy, hematologic disorders, and anemic FeLV-infected cats as well as preoperative conditioning for elective surgeries that may involve significant blood loss. Careful monitoring of therapy is necessary for optimal results. Several complications are associated with rHuEPO therapy. The production of anti-rHuEPO antibodies is the most significant and can be a life-threatening event. Alternatives to human EPO are being sought to provide beneficial effects while avoiding antibody formation.

Topics: Anemia; Animals; Cat Diseases; Cats; Chemotherapy, Adjuvant; Dog Diseases; Dogs; Erythropoietin; Recombinant Proteins

Topics: Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Myelophthisic; Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Erythrocyte Count; Erythropoiesis; Erythropoietin; Reticulocytes

A 20-month-old castrated male Korean shorthair cat was presented with a 3-week history of intermittent vomiting and anorexia, absolute erythrocytosis, and elevated erythropoietin levels. A diagnosis of splenic hemangiosarcoma was made by histopathology and immunohistochemical identification of factor VIII. Paraneoplastic erythrocytosis caused by a splenic hemangiosarcoma in a cat is described.

Topics: Animals; Cat Diseases; Cats; Erythropoietin; Factor VIII; Hemangiosarcoma; Male; Polycythemia; Splenic Neoplasms

The role of inflammation in the development and progression of chronic kidney disease (CKD) in cats is not well characterized. Hepcidin is a recently discovered acute-phase protein (APP) that plays an important role in iron metabolism and contributes to the development of anemia in humans with CKD.. To compare serum APP concentrations, iron status, and erythropoietin (EPO) concentrations in healthy cats and cats with naturally occurring CKD.. A total of 18 healthy control cats and 38 cats with CKD.. Prospective study. After complete physical examination and routine blood analysis, the following tests were performed: serum amyloid A (SAA), haptoglobin (HAP), EPO, serum iron and ferritin concentration as well as total iron-binding capacity (TIBC). Serum hepcidin-25 concentration was measured by ELISA kit designed for use in humans.. Mean SAA and hepcidin concentrations were significantly higher and mean total iron and TIBC were significantly lower in the CKD group (P < .05). There was a significant positive correlation between serum creatinine concentration (CRT) and 2 of the APPs (SAA and hepcidin; P < .05). Increases in SAA and hepcidin were associated with decreases in TIBC and hematocrit in the CKD group. Fourteen (37%) of the cats with CKD were anemic, and these cats had significantly lower TIBC (P < .05), suggesting a functional iron deficiency. There was no association between survival time and APP, iron status, or EPO concentrations.. Our data suggest that CKD in cats is associated with systemic inflammation and altered iron metabolism. With further validation in cats, hepcidin assays may help better characterize these relationships.

Topics: Acute-Phase Proteins; Anemia, Iron-Deficiency; Animals; Case-Control Studies; Cat Diseases; Cats; Erythropoietin; Female; Ferritins; Hematocrit; Hepcidins; Iron; Male; Prospective Studies; Renal Insufficiency, Chronic; Serum Amyloid A Protein

The discovery of expression of the erythropoietin receptor (EPO-R) on neoplastic cells has led to concerns about the safety of treating anaemic cancer patients with EPO. In addition to its endocrine function, the receptor may play a role in tumour progression through an autocrine mechanism. In this study, the expression of EPO, EPO-R and platelet-derived growth factor BB (PDGF-BB) was analysed in five feline and 13 canine osteosarcomas using immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). EPO expression was positive in all tumours by IHC, but EPO mRNA was only detected in 38% of the canine and 40% of the feline samples. EPO-R was expressed in all samples by quantitative RT-PCR (RT-qPCR) and IHC. EPO-R mRNA was expressed at higher levels in all feline tumours, tumour cell lines, and kidney when compared to canine tissues. PDGF-BB expression was variable by IHC, but mRNA was detected in all samples. To assess the functionality of the EPO-R on tumour cells, the proliferation of canine and feline osteosarcoma cell lines was evaluated after EPO administration using an alamarBlue assay and Ki67 immunostaining. All primary cell lines responded to EPO treatment in at least one of the performed assays, but the effect on proliferation was very low indicating only a weak responsiveness of EPO-R. In conclusion, since EPO and its receptor are expressed by canine and feline osteosarcomas, an autocrine or paracrine tumour progression mechanism cannot be excluded, although in vitro data suggest a minimal role of EPO-R in osteosarcoma cell proliferation.

Topics: Animals; Becaplermin; Bone Neoplasms; Cat Diseases; Cats; Cell Line, Tumor; Dog Diseases; Dogs; Erythropoietin; Immunohistochemistry; Osteosarcoma; Proto-Oncogene Proteins c-sis; Receptors, Erythropoietin; RNA

To characterize the biological effects of IM administration of a recombinant adeno-associated virus serotype 2 (rAAV2) vector containing feline erythropoietin (fEPO) cDNA and determine whether readministration of the vector or removal of muscle tissue at the injection sites alters those effects.. 10 healthy 7-week-old specific pathogen-free cats.. Cats received 1 X 10(7) infective units (iU; n = 3), 1 X 10(8) iU (3), or 1 X 10(9) iU (2) of rAAV2-fEPO vector IM (day 0). Two control cats received an rAAV2 vector containing the LacZ gene (1 X 10(9) iU, IM). In all cats, hematologic variables and serum fEPO concentration were measured at intervals; anti-rAAV2 antibody titer was measured on day 227. In cats that did not respond to treatment, the rAAV2-fEPO vector was readministered. Injection sites were subsequently surgically removed.. Compared with control cats, cats treated with 1 X 10(9) iU of rAAV2-fEPO vector had increased Hct and serum fEPO concentrations. One of these cats developed pure RBC aplasia; its Hct normalized following injection site excision. Cats receiving lower doses of vector had no response; on retreatment, 1 of those cats developed sustained erythrocytosis that persisted despite injection site removal and the others did not respond or responded transiently. Antibodies against rAAV2 were detected in all vector-treated cats.. Gene therapy may be an effective treatment for cats with hypoproliferative anemia. However, rAAV2-fEPO vector administration may result in pure RBC aplasia or pathologic erythrocytosis, and injection site removal does not consistently abolish the biological response.

Topics: Actins; Anemia; Animals; Antibodies, Viral; Cat Diseases; Cats; Dependovirus; DNA, Complementary; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Genetic Therapy; Genetic Vectors; Neutralization Tests; Promoter Regions, Genetic

Topics: Allopurinol; Animals; Cat Diseases; Cats; Erythropoietin; Euthanasia, Animal; Female; Ferrous Compounds; Interferon alpha-2; Interferon-alpha; Leishmaniasis; Male; Recombinant Proteins

To determine the activity of recombinant feline erythropoietin (rfEPO) in murine bioassays and evaluate its efficacy and safety in cats with erythropoietin-dependent nonregenerative anemia.. 26 cats (group 1, 19 cats with anemia attributed to chronic kidney disease [CKD]; group 2, 7 cats with CKD and recombinant human erythropoietin [rhEPO]-induced red cell aplasia [RCA]).. The rfEPO was synthesized by use of Chinese hamster ovary (CHO) cells transfected with feline erythropoietin complementary DNA. Preclinical assessments of rfEPO included an erythroid cell proliferation assay and measurements of reticulocytosis in Balb/C mice. Clinical assessments of cats included hematologic, biochemical, and clinical examinations during 12 (group 1) or 6 (group 2) months of rfEPO treatment.. Biological activity of rfEPO was broadly equivalent to rhEPO in preclinical murine bioassays. Median Hct and absolute reticulocyte count in cats increased significantly during the first 3 weeks of rfEPO treatment, and median Hct generally could be maintained within a target range of 30% to 40% with periodic adjustments of rfEPO doses. Unexpectedly, 5 cats in group 1 and 3 cats in group 2 that initially responded to rfEPO treatment again developed anemia that was refractory to additional rfEPO treatments, even at higher doses.. Treatment with rfEPO can reestablish active erythropoiesis in most cats with CKD, even those with anemia attributable to rhEPO-induced RCA. Unfortunately, development of RCA during treatment with CHO cell-derived recombinant erythropoietin proteins was not eliminated as a serious safety concern, even for this feline-specific preparation.

Topics: Anemia; Animals; Biological Assay; Blood Cell Count; Blood Chemical Analysis; Bone Marrow Cells; Cat Diseases; Cats; CHO Cells; Cricetinae; Cricetulus; DNA Primers; DNA, Complementary; Dose-Response Relationship, Drug; Erythroid Precursor Cells; Erythropoietin; Hemoglobins; Kidney Failure, Chronic; Mice; Mice, Inbred BALB C; Recombinant Proteins; Time Factors; Transfection

To investigate the clinicopathologic patterns of the erythropoietic response after renal transplantation in cats with chronic renal failure (CRF).. 14 cats with CRF undergoing renal transplantation.. Before and at intervals during a 6-month period after transplantation, serum creatinine and erythropoietin concentrations, Hct, erythrocyte indices, aggregate reticulocyte percentage, and iron variables were measured. Additionally, the number of transfusions administered to and any complications that developed in each cat were recorded.. In all cats, preoperative azotemia resolved within 6 days after renal transplantation. Two cats had a temporary increase in serum creatinine concentration secondary to an acute graft rejection episode. Anemia (defined as Hct < 28%) resolved in 10 cats 3 to 49 days after surgery. Resolution of anemia was delayed in 2 cats that had acute rejection episodes. Serum erythropoietin concentration and reticulocyte percentage were low preoperatively; values after surgery were highly variable. Compared with preoperative values, serum erythropoietin concentration increased 1 to 4 days after surgery in 11 cats; between days 5 and 58, another increase was detected in 9 cats. Serum iron concentrations were generally low before and 14 days after transplantation.. The erythropoietic response was highly variable in cats after renal transplantation, but anemia typically resolved within 1 month after surgery. A delay in resolution of anemia in cats may indicate poor graft function and inadequate iron stores, suggesting the need for further evaluation for concurrent illness.

Topics: Animals; Cat Diseases; Cats; Creatinine; Erythropoiesis; Erythropoietin; Female; Kidney Failure, Chronic; Kidney Transplantation; Male; Orchiectomy; Ovariectomy; Postoperative Period; Treatment Outcome

Chronic renal failure and the associated erythropoietin-responsive anemia afflicts over 2 million domestic cats in the United States, resulting in morbidity that can affect the owner-pet relationship. Although treatment of cats with recombinant human erythropoietin (Epo) protein can be effective, response to the drug often dissipates over time, probably due to the development of antibodies reactive with the human protein. As an alternate approach to the treatment of this disease, we have developed a recombinant adeno-associated virus vector containing the feline erythropoietin gene (rAAV/feEpo). This vector, when administered intramuscularly to normal healthy cats, caused a dose-related increase in hematocrit over a 7-week period after injection. Thus, the rAAV/feEpo vector holds promise as a simple, safe and effective therapy for the anemia of chronic renal failure in domestic cats.

Topics: Anemia; Animals; Bone Marrow Cells; Cat Diseases; Cats; Cell Line; Dependovirus; Dose-Response Relationship, Drug; Erythropoietin; Gene Expression; Gene Transfer Techniques; Genetic Engineering; Genetic Therapy; Genetic Vectors; Injections, Intramuscular; Kidney Failure, Chronic; Mice; Mice, SCID

Recombinant human GM-CSF (rhGM-CSF) and erythropoietin (rhEPO) were tested on chronically FIV-infected laboratory cats and uninfected specific-pathogen-free (SPF) cats. In Study 1, a total of eight cats (four cats per group of either infected or uninfected cats) received subcutaneous injection (twice a day) for 2 weeks with 5 microg/kg of rhGM-CSF, while seven cats (three SPF and four FIV-infected cats) served as the placebo-treated control cats. Four of eight rhGM-CSF-treated cats (two cats each from infected and uninfected groups) developed elevated WBC counts which peaked at Days 5-8 of treatment when compared to placebo-treated cats. The elevated WBC counts were attributed to the increase in either neutrophils, lymphocytes, eosinophils, monocytes, or their combinations. The RBC counts, platelet counts, and blood chemistry were not significantly affected by the treatment. Anti-rhGM-CSF antibodies were detected in six of eight rhGM-CSF-treated cats by Day 35 post-first treatment. All rhGM-CSF-treated infected cats but no placebo-treated infected cats had 1-2 log increase in FIV load in the PBMC during the treatment. In vitro studies suggest that rhGM-CSF has an effect on FIV replication in T cells but not in alveolar macrophages. Five of eight rhGM-CSF-treated cats had low-grade fever at 3-6 days of treatment. In Study 2, four cats per group of either infected or uninfected cats were treated (subcutaneously once a day) three times a week for 2 weeks with 100U/kg of rhEPO and monitored as before, while seven cats (three SPF and four FIV-infected cats) served as the placebo-treated control cats. All rhEPO-treated cats had a gradual increase in RBC, Hgb, and PCV counts which peaked at 2-4 weeks post-first rhEPO treatment, whereas none of the placebo-treated cats had significant increase in these parameters. The rhEPO-treated cats also developed elevated WBC counts consisting of either elevated neutrophils, lymphocytes, or their combination by 4 weeks post-first treatment but there was no statistical difference between rhEPO-treated and placebo-treated groups. None of the cats developed anti-rhEPO antibodies and no remarkable changes in blood chemistry, clinical signs, and FIV loads or FIV antibody titers were observed. Overall, rhEPO can be used safely on FIV-infected cats but the use of rhGM-CSF on FIV-infected cats should be performed with discretion.

Topics: Anemia; Animals; Blood Cell Count; Cat Diseases; Cats; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunodeficiency Virus, Feline; In Vitro Techniques; Lentivirus Infections; Male; Neutropenia; Recombinant Proteins; Virus Replication

To test efficacy and safety of recombinant human erythropoietin (r-HuEPO) administration in dogs and cats with naturally developing chronic renal failure.. Case series.. 6 client-owned dogs and 11 client-owned cats with chronic renal failure.. r-HuEPO was administered intravenously or subcutaneously. Erythropoietic effects were monitored by determining CBC, performing cytologic examination of bone marrow aspirates, and measuring serum iron concentration before and during treatment. Development of adverse effects was monitored by performing sequential clinical assessments, CBC, and serum biochemical tests and by measuring indirect blood pressure and anti-r-HuEPO antibody titers.. Administration of r-HuEPO increased RBC and reticulocyte counts, hemoglobin concentration, and Hct comparably in dogs and cats. Assessments of clinical well-being, including appetite, energy, weight gain, alertness, strength, and playfulness, were improved variably. Adverse effects, including anemia, anti-r-HuEPO antibody production, seizures, systemic hypertension, and iron deficiency, were demonstrated inconsistently in dogs and cats.. Anemia contributes to clinical manifestations of chronic renal failure in dogs and cats. Administration of r-HuEPO has the potential to resolve anemia and improve clinical well-being. However, its administration poses risks of antibody production and adverse effects associated with correction of RBC mass. Use of r-HuEPO in dogs and cats requires conscientious assessment of risks and benefits until homologous forms of erythropoietin are available.

Topics: Anemia; Animals; Blood Cell Count; Blood Chemical Analysis; Blood Pressure; Bone Marrow; Cat Diseases; Cats; Dog Diseases; Dogs; Erythrocyte Indices; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Seizures

Topics: Anemia; Animals; Cat Diseases; Cats; Erythropoietin; Hematocrit; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins

Erythropoiesis was evaluated in 5 cats at base line with normal PCV and then in the same cats with anemia induced by phlebotomy and in 5 other cats with nonregenerative anemia from community-acquired feline leukemia virus (FeLV) infection. The hematologic evaluation included complete blood cell and reticulocyte counts, marrow morphologic features, determination of serum erythropoietin concentrations by radioimmunoassay, ferrokinetic studies, and in vitro marrow culture of early erythroid progenitors (erythroid burst-forming units; BFU-E) and late erythroid progenitors (erythroid colony-forming units; CFU-E). Phlebotomized cats developed marrow erythroid hyperplasia and an increased reticulocyte count. Ferrokinetic studies revealed an increase in plasma iron turnover from 1.4 to 3.8 mg of Fe/dl of blood/day and RBC use from 50.4% to 78.5%. The mean CFU-E number and CFU-E/BFU-E ratio increased after phlebotomy, but the increase was not significant (P greater than 0.05). Serum erythropoietin values did increase significantly. In FeLV-infected cats, a nonregenerative anemia was demonstrated by marrow erythroid hypoplasia and a low total reticulocyte count. An increased percentage of rubriblasts and prorubricytes was observed in 4 of the 5 cats. Although serum erythropoietin values were high (321 +/- 123 mU/ml vs normal 14 +/- 1 mU/ml), ferrokinetic data revealed decreased erythropoiesis. Marrow culture studies in the FeLV-infected cats also revealed low numbers of BFU-E and CFU-E, but normal numbers of granulocyte-macrophage progenitors remained. Seemingly, the FeLV infection impaired the ability of feline marrow to respond physiologically to anemia.

Topics: Anemia; Animals; Biopsy, Needle; Bone Marrow; Cat Diseases; Cats; Erythropoiesis; Erythropoietin; Female; Iron; Kinetics; Leukemia; Leukemia Virus, Feline; Male; Reference Values; Regression Analysis

Erythropoietin concentrations were increased significantly (p less than 0.025) in nine cats with natural feline leukemia virus infection and associated erythroid aplasia compared to six clinically normal cats. Adult cats experimentally inoculated with the Kawakami-Theilen isolate of feline leukemia virus developed a progressive simultaneous increase in erythropoietin activity and decrease in packed cell volume. These findings indicate that erythroid aplasia associated with feline leukemia virus infection is not caused by a failure in erythropoietin production.

Topics: Anemia, Aplastic; Animals; Cat Diseases; Cats; Erythropoietin; Female; Hematocrit; Leukemia; Leukemia Virus, Feline; Male; Methylprednisolone; Methylprednisolone Acetate; Specific Pathogen-Free Organisms

Cats with induced sterile abscesses developed a hematologic disorder consistent with anemia of inflammation. Serum iron concentrations decreased while the abscess was present, but erythropoietin concentrations did not change significantly. Cobalt administration to control (healthy) cats resulted in polycythemia, reticulocytosis, and hyperferremia. Cats with abscesses responded to cobalt similarly; however, magnitudes of the polycythemia and reticulocytosis were less. Constant infusion of ferric citrate (IV) into cats with sterile abscesses maintained serum iron concentration in the normal to high range. The iron infusion did not prevent the anemia, but did enable the bone marrow to respond to the anemia.

Topics: Anemia; Animals; Cat Diseases; Cats; Cobalt; Erythrocyte Count; Erythropoiesis; Erythropoietin; Ferric Compounds; Hematocrit; Inflammation; Iron; Reticulocytes; Time Factors; Turpentine