losartan-potassium and Hyperlipidemias

Hemodialysis patients have uremic dyslipidemia, represented by elevated serum intermediate-density lipoprotein cholesterol (IDL-C) levels, and an increased cardiovascular mortality rate. This study was performed to determine the low-dose effects of the angiotensin II receptor blocker losartan and the angiotensin-converting enzyme inhibitor trandolapril on pulse wave velocity (PWV), which predicts cardiovascular morbidity and mortality in hemodialysis patients.. Serum lipid levels and PWV were monitored for 12 months in 64 hemodialysis patients who were administered low doses of losartan or trandolapril or a placebo.. At the start of the study, there were no differences in patient characteristics among the 3 groups. PWV tended to increase in the placebo group during the 12-month study period, but decreased significantly in the losartan and trandolapril groups, and decreases in PWV were similar in the losartan and trandolapril groups. There were no changes in blood pressure, hematocrit, erythropoietin dose, ankle-brachial index, serum lipid levels, serum 8-isoprostane levels, or serum C-reactive protein levels during the 12-month study period, but there was an increase in serum triglyceride levels in the losartan group and a decrease in serum IDL-C levels in the losartan and trandolapril groups.. In hemodialysis patients, trandolapril is as effective as losartan in decreasing PWV independent of its depressor effect and in suppressing elevated IDL-C levels. Long-term blockade of the renin-angiotensin system may have a beneficial effect on the acceleration of atherosclerosis and uremic dyslipidemia.

Topics: Aged; Anemia; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Comorbidity; Dinoprost; Drug Therapy, Combination; Erythropoietin; Female; Follow-Up Studies; Hematocrit; Humans; Hyperlipidemias; Indoles; Kidney Failure, Chronic; Lipids; Lipoproteins; Lipoproteins, LDL; Losartan; Male; Middle Aged; Prospective Studies; Renal Dialysis; Treatment Outcome; Vascular Resistance

Dyslipidemia is commonly observed in various kidney diseases, renal specific secreted erythropoietin (EPO) may participate in this process. However, how this process is regulated remains elusive.. Dyslipidemia was evaluated in chronic kidney disease and ischemia kidney injury animal model. Primary cultured adipocytes were harvested to investigate the lipid metabolic effect of EPO. Lipidemia was evaluated in EPO treated animals. Blood samples from cardiac surgery-induced kidney injury patient were collected to assess correlationship between EPO and lipidemia.. We found a decrease in secreted EPO and hypertriglyceridemia in chronic kidney disease (CKD) mice. In contrast, in renal ischemia animal model, increased EPO triggered by hypoxia signaling activation, was accompanied by decreased triglyceride (TG) in serum. Mechanistically, circulating EPO modulated JAK2-STAT5 signaling, which in turn enhanced lipid catabolism in peripheral adipose tissue and contributed to dysregulated lipidemia. Delivering of recombinant EPO into both wild type and CKD mice suppressed TG in serum by accelerating lipid catabolism in adipose tissue. In a cohort of patients diagnosed with acute kidney injury after cardiopulmonary bypass surgery, the decreased TG and cholesterol negatively correlated with increased EPO in serum.. This study depicted a new mechanism by which renal secreted EPO controlled lipidemia in kidney diseases including chronic kidney disease. Circulating EPO stimulated lipid catabolism by targeting JAK2-STATA5 signaling in peripheral adipose tissue, providing new therapeutic target for dyslipidemia treatment.. This work was supported by grants from the National Natural Science Foundation of China (Nos. 81700640 and 81970608).

Topics: Adipose Tissue; Animals; Disease Models, Animal; Erythropoietin; Hyperlipidemias; Hypoxia; Janus Kinase 2; Kidney; Kidney Diseases; Lipid Metabolism; Lipids; Male; Mice; Signal Transduction; STAT5 Transcription Factor

The haematopoietic activity of erythropoietin (EPO) is mediated by the classic EPO receptor (EpoR) homodimer, whereas tissue-protective effects are mediated by a heterocomplex between EpoR and the β-common receptor (βcR). Here, we investigated the effects of a novel, selective ligand of this heterocomplex - pyroglutamate helix B surface peptide (pHBSP) - in mice fed a diet enriched in sugars and saturated fats.. Male C57BL/6J mice were fed a high-fat high-sucrose diet (HFHS) for 22 weeks. pHBSP (30 μg·kg(-1) s.c.) was administered for the last 11 weeks. Biochemical assays, histopathological and immunohistochemical examinations and Western blotting were performed on serum and target organs (liver, kidney and skeletal muscle).. Mice fed with HFHS diet exhibited insulin resistance, hyperlipidaemia, hepatic lipid accumulation and kidney dysfunction. In gastrocnemius muscle, HFHS impaired the insulin signalling pathway and reduced membrane translocation of glucose transporter type 4 and glycogen content. Treatment with pHBSP ameliorated renal function, reduced hepatic lipid deposition, and normalized serum glucose and lipid profiles. These effects were associated with an improvement in insulin sensitivity and glucose uptake in skeletal muscle. Diet-induced overproduction of the myokines IL-6 and fibroblast growth factor-21 were attenuated by pHBSP and, most importantly, pHBSP markedly enhanced mitochondrial biogenesis in skeletal muscle.. Chronic treatment of mice with an EPO derivative, devoid of haematopoietic effects, improved metabolic abnormalities induced by a high-fat high-sucrose diet, by affecting several levels of the insulin signalling and inflammatory cascades within skeletal muscle, while enhancing mitochondrial biogenesis.

Topics: Animals; Blood Glucose; Dietary Fats; Dietary Sucrose; Erythropoietin; Fatty Liver; Hyperlipidemias; Insulin Resistance; Kidney; Liver; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Oligopeptides; Renal Insufficiency

Autoimmune hyperlipidemia (AIH) is a rare cause of secondary hyperlipidemia. A few cases of AIH have been reported in multiple myeloma.. A female in her fifties was referred to the outpatient clinic presenting with headache, blurred vision and skin rash. Physical examination with subsequent laboratory and histological examinations revealed severe hyperlipidemia secondary to secretory multiple myeloma with monoclonal IgG kappa protein and erythrocytosis secondary to a erythropoietin secreting adenoma in the liver.. Treatment for multiple myeloma (induction treatment and autologous hematological stem cell transplantation) gained partial remission and was associated with normalization of serum lipids. There was no need for further medical treatment of the hyperlipidemia. Three years after the initial treatment, serum concentrations of triglycerides and total cholesterol increased in parallel with monoclonal IgG kappa protein. Total cholesterol and triglycerides decreased and remained within the reference ranges after retreatment with a second autologous stem cell transplantation. Surgical removal of the hepatic adenoma caused normalisation of the erythropoietin concentration and resolution of the erythrocytosis. The present case reports two rare complications (AIH and erythrocytosis) to multiple myeloma and hepatic adenoma, with regression of complaints and normalisation of laboratory tests after adequate treatment of underlying diseases.

Topics: Adenoma, Liver Cell; Antibodies, Monoclonal; Anticholesteremic Agents; Antineoplastic Agents; Autoimmune Diseases; Erythropoietin; Fatty Acids, Omega-3; Female; Humans; Hyperlipidemias; Immunoglobulin A; Immunosuppressive Agents; Liver Neoplasms; Middle Aged; Multiple Myeloma; Polycythemia

Topics: Animals; Aorta; Aortic Diseases; Arteriosclerosis; Cholesterol Esters; Disease Models, Animal; Disease Progression; Erythropoietin; Genetic Predisposition to Disease; Humans; Hyperlipidemias; Lipids; Male; Rabbits; Recombinant Proteins

Plasma lipid disturbances are common among patients on maintenance haemodialysis and it seems to be important to evalate lipid status on r-Epo since this treatment of anemia is becoming substantial and so often used in that population. It appears more valuable because there are controversial data in the literature concerning this problem. The aim of the present study was to measure changes in serum lipid concentration in two comparable groups: I--11 patients (7f, 4m) aged 47 +/- 8 years receiving r-Epo s.c. during at least 6 months before HD and 2 years of HD with initial dose 3 x 50 u/kg b.w. and II--18 patients (7f, 11m) aged 45 +/- 8 years without r-Epo in that period of time. Following parameters were estimated every two months: total cholesterol (CH-C), HDL cholesterol (HDL-CH), LDL cholesterol (LDL-CH), triglycerides (TG), apolipoprotein B (Apo B).. 1. Subcutaneous therapy with r-Epo is an effective method of treatment of anemia in dialysis patients. 2. Long-term r-Epo treatment does not permanently influence the blood lipid profile in hemodialysed patients.

Topics: Adult; Anemia; Apolipoproteins B; Chronic Disease; Erythropoietin; Female; Humans; Hyperlipidemias; Injections, Subcutaneous; Kidney Diseases; Lipids; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

The burden of cardiac disease in dialysis patients is high. Congestive heart failure, ischemic heart disease, left ventricular hypertrophy, and systolic dysfunction occur frequently and are associated with an adverse prognosis. In addition, during dialysis therapy anemia, hypoalbuminemia, low blood pressure, and lower serum creatinine levels are adverse predictors of mortality. Risk factors for systolic dysfunction include older age, ischemic heart disease, hyperparathyroidism, and smoking. Risk factors for left ventricular hypertrophy include older age, hypertension, anemia, and diabetes mellitus. Interventions with potential for improving cardiomyopathy include normalization of hematocrit with erythropoietin, improved uremia therapy, and angiotensin-converting enzyme inhibitors. Trials to determine the most appropriate interventions to reduce the impact of cardiac disease in chronic uremia are urgently required.

Topics: Age Factors; Aged; Anemia; Angiotensin-Converting Enzyme Inhibitors; Canada; Cardiomyopathies; Cohort Studies; Comorbidity; Diabetes Mellitus; Echocardiography; Erythropoietin; Female; Hematocrit; Humans; Hyperlipidemias; Hyperparathyroidism; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Prevalence; Prognosis; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Risk Factors; Smoking; Survival Analysis; Systole

Topics: Adult; Carcinoma, Hepatocellular; Cholesterol; Erythropoietin; Humans; Hyperlipidemias; Lipoproteins; Liver; Liver Function Tests; Liver Neoplasms; Male; Phospholipids; Polycythemia; Triglycerides