losartan-potassium and Hyperhomocysteinemia

Despite the high prevalence and significant morbidity and mortality rates of chronic kidney disease (CKD) related to cardiovascular disease, it remains vastly understudied. Most of the current practice recommendations come from small under-powered prospective studies, retrospective reviews, and assuming patients with CKD will similarly benefit from medications and treatments as patients with normal renal function. In addition, because of the previous lack of a consistent definition of CKD and how to measure renal function, definitions of the degree of renal dysfunction have varied widely and compounded the confusion of these data. Remarkably, despite patients with CKD representing the group at highest risk from cardiovascular complications, even greater than patients with diabetes mellitus, there has been a systematic exclusion of patients with CKD from therapeutic trials. This review outlines our current understanding of CKD as a cardiovascular risk factor, treatment options, and the future directions that are needed to treat cardiovascular disease in patients with CKD.

Topics: Cardiovascular Diseases; Chronic Disease; Erythropoietin; Glomerular Filtration Rate; Humans; Hyperhomocysteinemia; Kidney Diseases; Myocardial Revascularization; Oxidative Stress; Recombinant Proteins; Risk Factors; United States

Anemia and hyperhomocysteinemia are risk factor of mortality of patients on dialysis. This study was conducted to assess the relationship of hemoglobin and homocysteine levels and mortality of patients on hemodialysis.. Fifty patients on hemodialysis and 20 healthy individuals were enrolled in the study. Blood samples were drawn for measurement of hematological parameters, serum iron, serum ferritin, transferrin saturation, and homocysteine levels. The patients were followed up for 1 year to determine the mortality rate and evaluate its association with anemia and hyperhomocysteinemia.. The majority the patients (54%) were not on erythropoietin therapy. Forty-three patients (86%) were anemic (hemoglobin < 11 g/dL). Serum ferritin was high (> 500 ng/mL) in 33 patients (66%). Mortality was 28% in 1 year (33% in anemic patients versus no death among patients with a hemoglobin level greater than 11 g/dL). The relative risk of mortality was increased by 1.58 with every 1 g/dL decrease in hemoglobin level. All of the patients had a high homocysteine level, and a significant difference was observed between the homocysteine levels of the patients on hemodialysis and the control group (P < .001). Hyperhomocysteinemia did not affect mortality. In multivariate Cox regression analysis, only hemoglobin level was associated with mortality.. Almost all of our patients on hemodialysis were anemic and this condition was a risk factor of mortality. Iron stores, however, were adequate in more than half of the patients. The reason of anemia could be untreated erythropoietin deficiency. Hyperhomocysteinemia was present in the majority of the patients, but it did not independently affect mortality.

Topics: Adolescent; Adult; Aged; Anemia; Erythropoietin; Female; Ferritins; Hemoglobins; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Renal Dialysis; Risk Factors; Transferrin; Young Adult

Elevated plasma homocysteine (Hcy) levels have been identified as a pathogenic factor causing a variety of pathological changes in different cells and tissues. In vertebrates, Hcy is produced solely from S-adenosylhomocysteine (AdoHcy) through the catalysis of AdoHcy-hydrolase. The direction of AdoHcy-hydrolase activity is determined by its cytosolic substrate concentrations, thereby controlling intracellular AdoHcy levels. Most S-adenosylmethionine (AdoMet)-dependent methyltransferases are regulated in vivo by the ratio of AdoMet/AdoHcy, which is termed "methylation potential" (MP). To test whether high rates of erythropoietin (EPO) expression is reduced by a low MP in vivo we choosed the model of increased EPO production following carbon monoxide (CO) exposure in rats in which high transcriptional activity is responsible for renal EPO production.. To induce a sustained hyperhomocysteinemia in rats, we infused i.v. a low or high dose of Hcy resulting in Hcy plasma levels of 87.4+/-6.2 and 300.8+/-23.7 mumol/l, respectively. Renal tissue contents of AdoHcy, AdoMet, and adenosine (Ado) were measured after freeze clamp by means of HPLC. Within 4h of CO exposure EPO serum levels increased from 13.6+/-0.4 (control) to 2254.8+/-278.3 mIU/ml. Only high dose of Hcy reduces both, the MP from 40.8+/-2.0 to 8.2+/-1.0 in the kidney as well as EPO serum levels by 40% compared to control rats.. Our data show that severe hyperhomocysteinemia (HHcy) affects the MP in the renal tissue and lowers EPO expression following CO induced intoxication. This result supports the concept that efficient EPO production requires an unimpaired MP.

Topics: Adenosylhomocysteinase; Animals; Carbon Monoxide; Erythropoietin; Homocysteine; Hyperhomocysteinemia; Male; Rats; Rats, Sprague-Dawley

To examine the possible relationships between recombinant human erythropoietin (rhEPO) therapy, serum folic acid and homocysteine levels in a cohort of stable, chronically hemodialyzed patients.. The study was cross-sectional in its first phase and consisted of 3 groups of subjects (group 1:6 healthy controls; group 2:7 dialyzed patients not receiving rhEPO; group 3: 14 patients on rhEPO therapy). Hematological and biochemical parameters were taken after an overnight fast in all subjects. The second phase of the study was prospective, and included 8 dialyzed patients, and investigated the effects of a 6-month period of folic acid supplementation (10 mg, 3 times a week) on the same parameters examined in the first phase of the study.. In the first part of the study hemoglobin levels were near-normal, or normal, in all patients. No differences in hemoglobin or hematocrit values were observed in the 3 groups. 80% of all hemodialyzed patients had low serum folic acid levels, irrespective of whether they were receiving rhEPO. Serum erythropoietin level was elevated in group 3 (23.3+/-10.4 mIU/ml). In group 2, serum erythropoietin level was not different from that of the healthy controls (13.5+/-11.2 vs. 8.0+/-5.4 mIU/ml, p = n.s.). Total serum homocysteine levels were elevated in all dialyzed patients (group 2: 24.7+/-9.2 micromol/l; group 3: 31.6+/-14.4 micromol/l), with a significant difference seen when comparing controls and those dialyzed patients on rhEPO therapy (8.7+/-2.2 vs. 31.6+/-14.4 micromol/l; p<0.05). Significant correlations (ANOVA) were observed between serum erythropoietin and folic acid levels (r = -0.382; p = 0.049), and between folic acid and homocysteine levels (r = -0.560; p = 0.002). In the second part of the study folic acid supplementation led to a highly significant reduction in homocysteine levels (20.9+/-4.9 vs. 11.9+/-2.5 micromol/l; p<0.0005). Two of 3 patients receiving rhEPO therapy, had rhEPO discontinued after commencing folic acid, as hemoglobin levels remained adequate, even without rhEPO.. In hemodialyzed patients, the presence of a near-normal hemoglobin level, irrespective of rhEPO therapy, implies efficient erythropoiesis. Without adequate folic acid reserves, folic acid deficiency may develop in these patients and this will aggravate already high homocysteine levels. Therefore, folic acid supplementation is warranted in hemodialyzed patients, especially in those patients with hemoglobin levels approaching normal. This treatment is safe and effective in reducing homocysteine levels, especially when given in high doses for prolonged periods of time.

Topics: Analysis of Variance; Case-Control Studies; Cross-Sectional Studies; Erythropoietin; Female; Folic Acid; Folic Acid Deficiency; Humans; Hyperhomocysteinemia; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis