losartan-potassium and Hypertrophy--Left-Ventricular

Topics: Anemia; Clinical Trials as Topic; Drug Resistance; Erythropoietin; Genetic Variation; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Practice Guidelines as Topic; Precision Medicine; Reference Values

Chronic untreated anemia or iron deficiency (ID) can result in an increased cardiac output, chronic sympathetic activation, left ventricular hypertrophy, and left ventricular dilation, leading to symptomatic chronic heart failure (CHF). Only in the past decade has there been an increase in interest in anemia and ID occurring in the course of CHF. The pharmacologic support in erythropoietin signaling or the correction in iron metabolism may activate molecular pathways that can protect the heart and prevent myocardial remodeling, and hence become a novel therapeutic approach in patients with CHF. Most of the data come from experimental models. Further studies, in particular performed in clinical settings, are warranted.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Heart Failure; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Myocardium; Risk Factors

The purpose was to evaluate changes in the left ventricular mass index (LVMi) among anemic chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients treated with recombinant human erythropoietin (EPO).. A systematic review of the literature, reporting LVMi for patients before and after EPO therapy, was performed. The change in LVMi from baseline to the end of treatment was calculated and stratified by severity of anemia at baseline, target hemoglobin (Hb), and stage of kidney disease.. Fifteen eligible studies involving 1731 patients were identified. Cohorts with severe anemia at baseline (<10 g/dl), when given EPO using a lower target level (Hb 12 g/dl or Hct > 36%). The effect size was similar in direction for both CKD and ESRD cohorts.. Aggregated results from multiple studies suggest that in severe anemia conventional Hb targets for EPO therapy are associated with a reduction in LVMi, but that in moderate anemia target Hb above 12 g/dl does not have a significant beneficial impact on LVMi compared with conventional targets.

Topics: Anemia; Biomarkers; Chronic Disease; Erythropoietin; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Kidney Failure, Chronic; Recombinant Proteins; Severity of Illness Index; Time Factors; Treatment Outcome

The use of erythropoietin (EPO) has revolutionized the treatment of anaemia associated with many conditions including chronic kidney disease (CKD). However, little is known of the cellular impact of EPO on the uraemic heart. The discovery that the EPO receptor (EPOR) is also expressed on non-haematopoietic cells including cardiomyocytes highlights a role of EPO beyond haematopoiesis. Animal models of heart failure have shown EPO can potentially reverse cardiac remodelling and improve myocardial function. Damage to the kidney, during uraemia, results in a decreased EPO production, which may render the uraemic heart more susceptible to damage and heart failure. Here we review current data on the cellular actions of EPO in models of left ventricular hypertrophy and heart failure and highlight parallels with the uraemic heart.

Topics: Cardiomyopathies; Erythropoietin; Fibrosis; Humans; Hypertrophy, Left Ventricular; Myocardium; Receptors, Erythropoietin; Risk Factors; Signal Transduction; Uremia; Ventricular Remodeling

End-stage renal disease is a troublesome health problem worldwide. The most usual renal replacement therapy is conventional haemodialysis (CHD), performed three times a week, 3.5-4 h per session. It has been proposed that this schedule is unphysiologic and that daily haemodialysis would be a more appropriate schedule. One of the variants of daily haemodialysis is the so-called short daily haemodialysis (SDHD), performed five to seven times per week, 1.5-3 h per session. The objective of this paper is to compare, through a systematic review, the clinical effectiveness and safety of SDHD versus CHD.. The following databases were searched: MEDLINE, EMBASE, NHS Centre for Reviews and Dissemination (HTA, DARE and NHS EED), Cochrane, ISI Web of Knowledge, IME and IBECS. Two independent reviewers decided which papers were to be included after applying inclusion and exclusion criteria. Any discrepancy was resolved by consensus. The quality of the included papers was measured using a quality scale developed for the purpose of this report.. Seventeen original articles were included. There were no randomized controlled trials. SDHD seems to be more effective than conventional dialysis. Patients on daily haemodialysis seem to present less vascular access problems, better control of hypertension and in turn a reduction in the antihypertensive treatment, better quality of life, lower incidence of ventricular hypertrophy, lower consumption of rHuEPO due to the better control of anaemia and a reduction in the use of phosphate binders as a consequence of the better control of plasmatic phosphorous.. SDHD might result in a better clinical effectiveness, mainly through a better control of the arterial tension and, therefore, a lower consumption of antihypertensive drugs, and a better quality of life than CHD.

Topics: Anemia; Antihypertensive Agents; Catheters, Indwelling; Erythropoietin; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Nutritional Status; Quality of Life; Recombinant Proteins; Renal Dialysis; Safety; Treatment Outcome

Recombinant human erythropoietin has been used for more than 20 years for the treatment of renal anaemia, with epoetin-alfa and -beta representing the common traditional preparations. By the modification of the molecule's carbohydrate moiety or structure a longer duration of erythropoietin receptor stimulation was achieved. The administration of these new molecules (darbepoetin, C.E.R.A.) once or twice a month is also sufficient to achieve serum haemoglobin target levels, making the treatment safer and more comfortable both for the patients and the personnel. These recently developed synthetic erythropoietin receptor stimulating molecules, along with recombinant human erythropoietin, are together called "Erythropoiesis Stimulating Agents". In haemodialysed patients the intravenous route is preferred, but the subcutaneous administration can substantially reduce dose requirements. In praedialysed, transplanted or peritoneally dialysed patients, erythropoiesis stimulating agents should preferably be given subcutaneously both for economic and practical reasons. There are ongoing clinical trials with erythropoiesis stimulating molecules that can be administered by inhalation or per os. Current evidence suggests that the serum haemoglobin level should preferably not exceed 12 g/dl with the use of erythropoiesis stimulating agents. No cardiovascular protective effect of higher serum haemoglobin levels was demonstrated in two large clinical trials. Further well-designed studies are necessary to set evidence-based haemoglobin targets for erythropoiesis stimulating treatment. Arguments for a more widespread use of agents with extended duration include medical, financial and patient satisfaction reasons. The release of new erythropoiesis stimulating agents may further simplify the treatment of renal anaemia.

Topics: Administration, Cutaneous; Administration, Inhalation; Administration, Oral; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Heart Failure; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Infusions, Intravenous; Kidney Failure, Chronic; Receptors, Erythropoietin; Recombinant Proteins; Renal Dialysis

Improving anemia in patients with chronic renal failure (CRF) and congestive heart failure (CHF) also improves left ventricular hypertrophy (LVH). No previous meta-analyses have been conducted to further examine this association, including the association between LVH and mortality in these patients.. Literature searches on MEDLINE, EMBASE, and OVID were performed using Cochrane Library protocols. Two hundred sixteen abstracts were reviewed preliminarily for inclusion in the meta-analysis of epoetin alfa, anemia and 5 pre-selected parameters of LVH. One hundred seventy-nine abstracts were reviewed for LVH and mortality. The predominant hematologic and left ventricular function changes observed during epoetin alfa treatment in patients with CHF and CRF are (1) increases in hemoglobin (Hb) and hematocrit (Hct); (2) decreases in left ventricular mass (LVM) and LVM index; (3) increase in ejection fraction (EF); and (4) decreases in left ventricular end-diastolic and end-systolic volume. Three independent factors-target Hb, duration of disease, and duration of follow-up-each had a statistically significant association with Hb, Hct, and EF, respectively. A separate meta-analysis using 3 risk models showed LVH is strongly and positively associated with both cardiovascular and all-cause mortality, with two- to three-fold increases in risk.. LVH is common in patients with CRF and CHF. Current findings indicate epoetin alfa therapy results in anemia amelioration, as evidenced by higher Hb and Hct levels, and reduction of key LVH parameters. LVM regression is associated with lower incidence of cardiovascular-related morbidity and mortality, therefore epoetin alfa therapy may provide a survival benefit.

Topics: Adult; Anemia; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Regression Analysis; Ventricular Function, Left

Chronic kidney disease (CKD) affects over 6.2 million people in the U.S. and most commonly results from diabetes and/or hypertension. Patients with CKD have an increased risk of anemia and hypertension. Anemia occurs early in CKD and can be effectively treated with epoetin alfa. Hypertension can be managed with lifestyle modifications and medications. Nurses play a vital role in managing these patients by providing early CKD/anemia screening and intervention, education, patient monitoring, and support for patients and caregivers.

Topics: Algorithms; Anemia; Decision Trees; Diabetes Complications; Erythropoietin; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Life Style; Mass Screening; Nurse's Role; Quality Assurance, Health Care; Risk Factors; Severity of Illness Index; United States

Topics: Anemia; Erythropoietin; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic

Topics: Adaptation, Physiological; Anemia; Cardiovascular System; Cognition Disorders; Drug Costs; Epoetin Alfa; Erythropoietin; Exercise; Heart Failure; Hematocrit; Hemodynamics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Iron; Kidney Failure, Chronic; Multicenter Studies as Topic; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Reference Values; Renal Dialysis; Risk; Thrombophilia; Treatment Outcome

Topics: Anemia; Erythropoietin; Heart; Humans; Hypertrophy, Left Ventricular; Recombinant Proteins; Renal Circulation

There is a clear relationship between anaemia and cardiovascular risk in chronic renal failure (CRF) patients. Left ventricular hypertrophy (LVH) is present in about three-quarters of patients starting dialysis, and is a strong predictor of mortality. Anaemia contributes to the development of LVH, mainly via increased cardiac output. In some patients, anaemia results in an increase in LV mass, while in others it also results in LV end-diastolic volume dilatation. These changes increase the risk of arrhythmias, myocardial infarction and myocardial fibrosis. The lower the haemoglobin, the more likely it is that LVH and heart failure will develop. Furthermore, a haemoglobin of < 11 g/dl is associated with increased morbidity and mortality. Partial correction of anaemia with epoetin leads to a partial, but not complete, reversal of LVH. One large prospective study (Lombardy Registry) found that epoetin treatment was accompanied by a 30% reduction in crude relative risk of mortality. A progressive reduction in the relative risk of general and cardiovascular mortality was found with increasing haematocrit, with and without adjustment for co-morbid conditions. Mean hospitalizations also decreased with increasing haematocrit. The long-term effects of normalized haematocrit/haemoglobin values in uraemic patients have not yet been evaluated exhaustively in prospective, randomized, multicentre studies. Epoetin treatment has been shown to induce lasting improvements in patients' sense of well-being, reduce fatigue, increase appetite and work capacity, and improve exercise tolerance, libido and work performance. Further studies are needed to demonstrate whether greater haemoglobin concentrations are associated with greater improvements in quality of life during epoetin treatment.

Topics: Anemia; Animals; Erythropoietin; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Quality of Life

Topics: Anemia; Clinical Trials as Topic; Erythropoietin; Humans; Hypertrophy, Left Ventricular; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Erythropoietin; Heart Failure; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Morbidity; Recombinant Proteins; Renal Replacement Therapy; Risk Factors

Recombinant human erythropoietin (r-HuEPO) effectively corrects the anemia of end stage renal disease (ESRD). Development or aggravation of hypertension has been the most commonly reported side-effect of r-HuEPO treatment. Placebo controlled trials have shown incidence rates ranging from 16-21%. Renal failure itself obviously is a prerequisite in the pathogenesis of r-HuEPO-induced hypertension, since it was never observed in anemic patients without renal disease. Increased whole blood viscosity and/or reduced hypoxic vasodilatation due to the rise in hematocrit may play a role in the development of hypertension at high concentrations of hematocrit. However, at hematocrit levels around 30% additional hypertensinogenic effects of r-HuEPO treatment seem likely. Endothelin and prostanoids are possible mediators of this effect. Left ventricular hypertrophy (concentric and eccentric), which can be due to hypertension and anemia, is commonly observed in ESRD patients and has been shown to be a predictor of cardiac morbidity and mortality in these patients. Following correction of anemia with r-HuEPO measures of left ventricular hypertrophy decrease by about 18% within a year. Normalization, though, is generally not achieved and in patients with r-HuEPO induced hypertension the increase of blood pressure may oppose the beneficial effects of r-HuEPO treatment on cardiac hypertrophy.

Topics: Anemia; Animals; Erythropoietin; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Recombinant Proteins

To study the specific features of diastolic dysfunction (DD) in different types of left ventricular (LV) hypertrophy (LVH) in patients with end-stage renal failure (ESRF) and to estimate the cardioprotective effect of erythropoietin.. 107 patients (57 women and 50 men) aged 22 to 63 years with ESRF were examined. The follow-up was 18 months. LV ejection fraction, peak early diastolic filling rate, peak late diastolic filling rate, their ratio, LV isovolumic relaxation time, LV end-diastolic diameter, LV end-diastolic volume, LV end-diastolic diameter index (EDDI), LV posterior wall and ventricular septal thickness, and LV mass index were determined. J. Gottdiener's classification based on the calculation of EDDI and LV relative wall thickness was used to estimate LV geometry. Erythropoietin was given to patients with the baseline level of hemoglobin (Hb) < 110 g/l or hematocrit (Ht) < 33%; and iron (III) hydroxide sucrose complex was used to those with ferritin < 100 microg/l or transferrin saturation < 20%. The target level of blood pressure was 130/80 mm Hg; Hb was less than 110 g/l for women and 120 g/l for men; Ht, > 33%.. The patients with ESRF were found to have different types of DD and LVH, the severity of which correlated with the magnitude of renal anemia and arterial hypertension (AH). Adequate correction of anemia and AH promoted the transition of more to less severe DD and LVH and in a number of cases the recovery of LV structure and function.. ESRF is characterized by different types of DD, which are pathogenetically closely related to different types of LVH. Adequate correction of renal anemia and AH may cause a significant reduction and, in a number of cases, alleviate VLH, and normalize LV systolic and diastolic functional values.

Topics: Adult; Cardiotonic Agents; Diastole; Echocardiography; Epoetin Alfa; Erythropoietin; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Treatment Outcome; Ventricular Function, Left; Young Adult

We observed 93 patients with CRS 2,4,5 types having anemia, systolic dysfunction of left ventricle (LV) - EF ≤45% and heart failure functional class (FC) II-IV (NYHA). All patients are under HD and were treated with EPO 3 times per week in a period of 6 months. We revealed improvement of LV EF 4,3 % and HF FC after EPO treatment and concluded that EPO therapy causes regression of LV hypertrophy, improves LV function and quality of life.

Topics: Anemia; Cardio-Renal Syndrome; Drug Administration Schedule; Erythropoietin; Humans; Hypertrophy, Left Ventricular; Quality of Life; Renal Dialysis; Treatment Outcome; Ventricular Function, Left

The acute administration of high-dose erythropoietin (EPO) on reperfusing ischaemic myocardium has been reported to halve myocardial infarct (MI) size in preclinical studies, but its effect in ST elevation myocardial infarction patients undergoing primary percutaneous coronary intervention (PPCI) remains unknown. We investigated whether high-dose EPO administered as an adjunct to PPCI reduces MI size.. Double-blinded, randomised, placebo-controlled.. Single tertiary cardiac centre.. Fifty-one ST elevation myocardial infarction patients undergoing PPCI.. Patients were randomly assigned to receive either a single intravenous bolus of EPO (50,000 IU) prior to PPCI with a further bolus given 24 h later (n=26) or placebo (n=25).. MI size measured by 24 h area under the curve troponin T and cardiac magnetic resonance imaging performed on day 2 and at 4 months.. EPO treatment failed to reduce MI size (troponin T area under the curve: 114.6±78 μg/ml EPO vs 100.8±68 μg/ml placebo; infarct mass by cardiac magnetic resonance: 33±16 g EPO vs 25±16 g placebo; both p>0.05). Unexpectedly, EPO treatment doubled the incidence of microvascular obstruction (82% EPO vs 47% placebo; p=0.02) and significantly increased indexed left ventricular (LV) end-diastolic volumes (84±10 ml/m(2) EPO vs 73±13 ml/m(2) placebo; p=0.003), indexed LV end-systolic volumes (41±9 ml/m(2) EPO vs 35±11 ml/m(2) placebo; p=0.035) and indexed myocardial mass (89±16 g/m(2) EPO vs 79±11 g/m(2) placebo; p=0.03). At 4 months, there were no significant differences between groups.. High-dose EPO administered as an adjunct to PPCI failed to reduce MI size. In fact, EPO treatment was associated with an increased incidence of microvascular obstruction, LV dilatation and increased LV mass. Clinical Trial Registration Information http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=4058 Unique Identifier=Study ID 4058.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Biomarkers; Coronary Circulation; Double-Blind Method; Drug Administration Schedule; Erythropoietin; Female; Hematinics; Humans; Hypertrophy, Left Ventricular; Injections, Intravenous; London; Magnetic Resonance Imaging; Male; Microcirculation; Middle Aged; Myocardial Infarction; Myocardium; Placebo Effect; Recombinant Proteins; Stroke Volume; Time Factors; Treatment Outcome; Troponin T; Ventricular Function, Left

Anemia is common among patients with chronic kidney disease (CKD). The introduction of erythropoietin treatment has changed anemia management, but the therapeutic hemoglobin (Hb) target is still under debate, and clinical evidence for its effect on cardiac functions and QOL is sparse.. A 16-week dose-response study and a 32-week follow-Up study were combined. After correcting anemia of less than 10 g/dl in pre-dialysis Japanese CKD patients, a higher Hb target (12-13 g/dl) by darbepoetin alfa (DPO) was compared with the conventional Hb target by epoetin alfa (EPO). Outcomes were anemia correction, management of the left ventricular mass index (LVMI) and QOL scores.. No significant difference was seen in Hb at baseline and week 16, but a significant difference was recorded at week 34 (12.34 +/- 0.93 g/dl for DPO and 10.43 +/- 0.90 g/dl for EPO). In both groups, LVMI decreased similarly until week 16, but the decrease of EPO was retarded, and a significant difference between LVMI was seen only in DPO at week 34 (100.7 +/- 16.6 g/m(2) for DPO and 110.9 +/- 25.2 g/m(2) for EPO). Relationships between Hb and LVMI change at week 34 were examined by stratifying Hb into four groups (Hb <10 g/dl, 10 g/dl < or = Hb <11 g/dl, 11 g/dl < or = Hb <12 g/dl and 12 g/dl < or = Hb), and a decrease of LVMI was prominent in the 12 g/dl < or = Hb group. Correction of anemia to 11 g/dl or more led to improved QOL scores. No safety difference was observed among the treatments.. Targeting a higher Hb around 12 g/dl was more beneficial than targeting conventional Hb in terms of reduction of LVMI and QOL. Further studies to determine the appropriate Hb target are necessary.

Topics: Adult; Aged; Asian People; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Heart Ventricles; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Japan; Kidney Failure, Chronic; Male; Middle Aged; Quality of Life; Recombinant Proteins

Although left ventricular hypertrophy (LVH) is a characteristic finding in hemodialysis (HD) populations, few risk factors for progressive LVH have been identified.. As part of a multinational, blinded, randomized, controlled trial that demonstrated no effect of hemoglobin targets on LV size, 596 incident HD patients, without symptomatic cardiac disease or cardiac dilation, had baseline echocardiograms within 18 months of starting dialysis and subsequently at 24, 48, and 96 weeks later. A wide array of baseline risk factors were assessed, as were BP and hemoglobin levels during the trial.. The median age and duration of dialysis were 51.5 years and 9 months, respectively. LV mass index (LVMI) rose substantially during follow-up (114.2 g/m(2) at baseline, 121 at week 48, 123.4 at week 48, and 128.3 at week 96), as did fractional shortening, whereas LV volume (68.7, 70.1, 68.7, and 68.1 ml/m(2)) and E/A ratio remained unchanged. At baseline, the only multivariate associations of LVMI were gender and N terminal pro-B type natriuretic peptide. Comparing first and last echocardiograms in those without LVH at baseline, independent predictors of increase in LVMI were higher time-integrated systolic BP and cause of ESRD. An unadjusted association between baseline LVMI and subsequent cardiovascular events or death was eliminated by adjusting for age, diabetes, systolic BP, and N terminal pro-B type natriuretic peptide.. Progressive concentric LVH and hyperkinesis occur in HD patients, which is partly explained by hypertension but not by a wide array of potential risk factors, including anemia.

Topics: Anemia; Canada; Disease Progression; England; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Linear Models; Logistic Models; Male; Middle Aged; Odds Ratio; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Renal Dialysis; Risk Factors; Time Factors; Ultrasonography

Partial correction of anemia in patients with chronic kidney disease (CKD) reduces left ventricular hypertrophy (LVH), which is a risk factor for cardiovascular (CV) morbidity, but complete correction of anemia does not improve CV outcomes. Whether LV geometry associates with CV events in patients who are treated to different hemoglobin (Hb) targets is unknown. One of the larger trials to study the effects of complete correction of anemia in stages 3 to 4 CKD was the Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta (CREATE) trial. Here, we analyzed echocardiographic data from CREATE to determine the prevalence, dynamics, and prognostic implications of abnormal LV geometry in patients who were treated to different Hb targets. The prevalence of LVH at baseline was 47%, with eccentric LVH more frequent than concentric. During the study, LVH prevalence and mean left ventricular mass index did not change significantly, but LV geometry fluctuated considerably within 2 yr in both groups. CV event-free survival was significantly worse in the presence of concentric LVH and eccentric LVH compared with the absence of LVH (P = 0.0009 and P < or = 0.0001, respectively). Treatment to the higher Hb target associated with reduced event-free survival in the subgroup with eccentric LVH at baseline (P = 0.034). In conclusion, LVH is common and associates with poor outcomes among patients with stages 3 to 4 CKD, although both progression and regression of abnormal LV geometry occur. Complete anemia correction may aggravate the adverse prognosis of eccentric LVH.

Topics: Adult; Aged; Anemia; Cardiovascular Diseases; Disease-Free Survival; Echocardiography; Erythropoietin; Female; Heart Ventricles; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; Recombinant Proteins; Renal Insufficiency, Chronic; Risk Factors; Time Factors; Treatment Outcome

After acute normovolemic hemodilution (ANH), improvement of the rheologic conditions may contribute to optimize tissue oxygen delivery and attenuate ischemia-reperfusion injuries. It was hypothesized that ANH would confer additional cardioprotection in patients with ventricular hypertrophy undergoing open heart surgery.. This study was a randomized controlled trial. Forty patients scheduled for elective aortic valve replacement were randomly assigned to a control group (standard care) or an ANH group (target hematocrit level of 28%). All patients were managed with standard myocardial preservation techniques (cold blood cardioplegia, anesthetic preconditioning). The outcome measures included the release of myocardial enzymes, perioperative hemodynamic changes, the need for pharmacologic cardiovascular support, and cardiac complications.. In the ANH group, the postoperative release of troponin I (mean peak plasma concentrations, 1.7 ng/mL; 95% confidence interval, 1.4-2.1 ng/mL) and myocardial fraction of creatine kinase (22 U/L; range, 18-24 U/L) was significantly lower than in the control group (3.6 [range, 3.0-4.2] ng/mL and 45 [range, 39-51] U/L, respectively). In addition, requirement for inotropic support was significantly lower and fewer hemodiluted patients presented adverse cardiac events. After ANH, there was a significant decrease in heart rate (-11 +/- 6%) and rate-pressure product (-16 +/- 8%) until the aortic cross-clamping time and, at the end of surgery, the circulating levels of erythropoietin (EPO) were higher than in control patients (13.6 +/- 4.2 mUI/mL vs. 7.3 +/- 2.4 mUI/mL; p < 0.05).. Besides conventional cardiac preservation techniques, preoperative ANH further attenuates myocardial injuries. Optimization of preischemic myocardial oxygen delivery and/or consumption and the postconditioning effects of endogenous EPO are potential mechanisms for ANH-induced cardioprotection.

Topics: Aged; Aortic Valve Stenosis; Blood Pressure; Blood Volume; Cardiac Output; Creatine Kinase, MB Form; Echocardiography; Electrocardiography; Erythropoietin; Female; Heart Valve Prosthesis Implantation; Hemodilution; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Myocardium; Preoperative Care; Severity of Illness Index; Treatment Outcome; Troponin I

To study efficacy and safety of long-term administration of epoetin and iron preparations in glomerulonephritis (GN) patients with chronic kidney disease (CKD) of stage III-IV in systemic diseases.. A total of 189 patients at predialysis stage of CKD (glomerular filtration rate between 15 and 60 ml/min) were randomized into 3 groups depending on GN etiology: primary GN (group 1, 123 patients), GN in systemic diseases (group 2, 45 patients), controls (group 3, 21 patients). Anemia was characterized not only by red cells indices but also by the level of serum ferritin, C-reactive protein (CRP), saturation of transferrin with iron. Remodeling of the heart was determined in all the patients at dopplerechocardiography estimating left ventricular myocardial mass, relative thickness of its wall.. Correction of anemia was achieved in all the patients with GN and CKD of stage III-IV in systemic diseases despite the activity of systemic disease (high blood level of CRP) and persistent nephritis activity (high proteinuria). In many patients from groups 1 and 2 who were initially diagnosed to have left ventricular hypertrophy (LVH) of excentric type LVH regressed after 6 months of anemia correction. In group 3 with untreated anemia frequency of LVH increased.. Treatment of anemia in GN patients with CKD of stage III-IV in systemic diseases needed higher doses of epoetin and parenteral iron preparations compared to patients with the above stages of CKD with primary GN.

Topics: Anemia, Iron-Deficiency; C-Reactive Protein; Disease Progression; Dose-Response Relationship, Drug; Echocardiography, Doppler; Epoetin Alfa; Erythropoietin; Female; Ferritins; Follow-Up Studies; Glomerular Filtration Rate; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Iron; Iron Compounds; Kidney Failure, Chronic; Male; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

Morbidity and mortality rates in hemodialysis patients remain excessive. Alterations in the delivery of dialysis may lead to improved patient outcomes.. To compare the effects of frequent nocturnal hemodialysis vs conventional hemodialysis on change in left ventricular mass and health-related quality of life over 6 months.. A 2-group, parallel, randomized controlled trial conducted at 2 Canadian university centers between August 2004 and December 2006. A total of 52 patients undergoing hemodialysis were recruited.. Participants were randomly assigned in a 1:1 ratio to receive nocturnal hemodialysis 6 times weekly or conventional hemodialysis 3 times weekly.. The primary outcome was change in left ventricular mass, as measured by cardiovascular magnetic resonance imaging. The secondary outcomes were patient-reported quality of life, blood pressure, mineral metabolism, and use of medications.. Frequent nocturnal hemodialysis significantly improved the primary outcome (mean left ventricular mass difference between groups, 15.3 g, 95% confidence interval [CI], 1.0 to 29.6 g; P = .04). Frequent nocturnal hemodialysis did not significantly improve quality of life (difference of change in EuroQol 5-D index from baseline, 0.05; 95% CI, -0.07 to 0.17; P = .43). However, frequent nocturnal hemodialysis was associated with clinically and statistically significant improvements in selected kidney-specific domains of quality of life (P = .01 for effects of kidney disease and P = .02 for burden of kidney disease). Frequent nocturnal hemodialysis was also associated with improvements in systolic blood pressure (P = .01 after adjustment) and mineral metabolism, including a reduction in or discontinuation of antihypertensive medications (16/26 patients in the nocturnal hemodialysis group vs 3/25 patients in the conventional hemodialysis group; P < .001) and oral phosphate binders (19/26 patients in the nocturnal hemodialysis group vs 3/25 patients in the conventional dialysis group; P < .001). No benefit in anemia management was seen with nocturnal hemodialysis.. This preliminary study revealed that, compared with conventional hemodialysis (3 times weekly), frequent nocturnal hemodialysis improved left ventricular mass, reduced the need for blood pressure medications, improved some measures of mineral metabolism, and improved selected measures of quality of life.. isrctn.org Identifier: ISRCTN25858715.

Topics: Adult; Aged; Anemia; Blood Pressure; Calcium Phosphates; Circadian Rhythm; Erythropoietin; Female; Hematocrit; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Magnetic Resonance Imaging; Male; Middle Aged; Parathyroid Hormone; Quality of Life; Renal Dialysis

Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established.. We randomly assigned 603 patients with an estimated glomerular filtration rate (GFR) of 15.0 to 35.0 ml per minute per 1.73 m2 of body-surface area and mild-to-moderate anemia (hemoglobin level, 11.0 to 12.5 g per deciliter) to a target hemoglobin value in the normal range (13.0 to 15.0 g per deciliter, group 1) or the subnormal range (10.5 to 11.5 g per deciliter, group 2). Subcutaneous erythropoietin (epoetin beta) was initiated at randomization (group 1) or only after the hemoglobin level fell below 10.5 g per deciliter (group 2). The primary end point was a composite of eight cardiovascular events; secondary end points included left ventricular mass index, quality-of-life scores, and the progression of chronic kidney disease.. During the 3-year study, complete correction of anemia did not affect the likelihood of a first cardiovascular event (58 events in group 1 vs. 47 events in group 2; hazard ratio, 0.78; 95% confidence interval, 0.53 to 1.14; P=0.20). Left ventricular mass index remained stable in both groups. The mean estimated GFR was 24.9 ml per minute in group 1 and 24.2 ml per minute in group 2 at baseline and decreased by 3.6 and 3.1 ml per minute per year, respectively (P=0.40). Dialysis was required in more patients in group 1 than in group 2 (127 vs. 111, P=0.03). General health and physical function improved significantly (P=0.003 and P<0.001, respectively, in group 1, as compared with group 2). There was no significant difference in the combined incidence of adverse events between the two groups, but hypertensive episodes and headaches were more prevalent in group 1.. In patients with chronic kidney disease, early complete correction of anemia does not reduce the risk of cardiovascular events. (ClinicalTrials.gov number, NCT00321919 [ClinicalTrials.gov].).

Topics: Anemia; Cardiovascular Diseases; Disease Progression; Erythropoietin; Female; Follow-Up Studies; Glomerular Filtration Rate; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Quality of Life; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic; Survival Analysis

Left ventricular hypertrophy (LVH) frequently complicates chronic renal insufficiency. Anemia is also common in these patients and may contribute to LVH.. We conducted an open-label interventional trial to evaluate the effect of recombinant erythropoietin (rhEPO) on left ventricular mass index (LVMI) in anemic patients with renal insufficiency. Adults with creatinine clearance 10 to 30 mL/min (nondiabetics) or 20 to 40 mL/min (diabetics) were recruited, and rhEPO was given to those with anemia (hemoglobin level <10 g/dL). Baseline and 6-month LVMI and LVH (LVMI >130 g/m(2) in men and >100 g/m(2) in women), hemoglobin levels, creatinine clearance, blood pressure, medications, and medical history were obtained. Forty anemic and 61 nonanemic control subjects were enrolled.. Overall, the prevalence of LVH was 68.3% (95% CI 58.3-77.2), and entry hemoglobin level was the only significant predictor of baseline LVH (adjusted OR 0.69 per g/dL increase in hemoglobin, 95% CI 0.50-0.94). After 6 months, LVMI decreased in anemic patients receiving rhEPO (142 +/- 56 vs. 157 +/- 56 g/m(2)) (P= 0.007), with an increase in hemoglobin (11.3 +/- 1.9 vs. 9.1 +/- 0.7 g/dL) (P= 0.001). There were no changes in LVMI or hemoglobin level among controls. After adjusting for confounders and change in hemoglobin, receipt of rhEPO was associated with a significant reduction in LVMI (P= 0.01).. Treatment with rhEPO was not independently associated with significant changes in blood pressure or renal function. LVH is a common finding in chronic renal insufficiency and is associated with lower hemoglobin levels. Treatment with rhEPO may decrease LVH in patients with severe renal insufficiency and anemia.

Topics: Adult; Aged; Anemia; Blood Pressure; Erythropoietin; Female; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Prevalence; Recombinant Proteins; Severity of Illness Index

Left ventricular hypertrophy (LVH) and inflammation independently increase risk for death in people who receive hemodialysis. A nonrandomized, controlled trial was conducted of the effect of short daily (6 sessions/wk of 3 h each) or conventional (three sessions/wk of 4 h each) hemodialysis on LVH and inflammatory factors. A total of 26 short daily hemodialysis and 51 matched conventional hemodialysis patients were enrolled, and baseline and 12-mo measures of echocardiographic left ventricular mass index (LVMI), serum C-reactive protein (CRP), serum calcium and phosphorus, and erythropoietin resistance index were collected. Baseline characteristics were similar between groups except that hemoglobin and serum calcium were lower and serum phosphorus was higher in the short daily hemodialysis group. At 12-mo follow-up, short daily hemodialysis patients experienced a 30% decrease in LVMI (154 +/- 33 to 108 +/- 25; P < 0.0001). After adjustment for potential confounders, short daily hemodialysis (beta = -41.63, P = 0.03) and percentage decrease in serum phosphorus (beta = -0.12, P = 0.04) predicted a 12-mo decrease in LVMI. Among short daily hemodialysis patients, there were significant reductions in median CRP levels [1.22 interquartile range (IQR) (0.37 to 3.70) to 0.05 IQR (0.05 to 1.17); P < 0.01] and erythropoietin resistance index [19.5 IQR (8.6 to 37.6) to 10.5 IQR (5.5 to 14.6); P < 0.001]. There were no significant changes in LVMI, CRP, or erythropoietin resistance index in the conventional hemodialysis group. Short daily hemodialysis is associated with improved fluid and phosphorus management and a reduction in LVH and inflammatory factors compared with conventional hemodialysis. Future trials are needed to determine whether short daily hemodialysis can reduce morbidity and mortality in this high-risk population.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcium; Drug Resistance; Erythropoietin; Female; Humans; Hypertrophy, Left Ventricular; Inflammation Mediators; Kidney Failure, Chronic; Male; Middle Aged; Phosphorus; Prospective Studies; Recombinant Proteins; Renal Dialysis; Time Factors

This randomized clinical trial is designed to assess whether the prevention and/or correction of anemia, by immediate versus delayed treatment with erythropoietin alfa in patients with chronic kidney disease, would delay left ventricular (LV) growth. Study design and sample size calculations were based on previously published Canadian data.. One hundred seventy-two patients were randomly assigned. The treatment group received therapy with erythropoietin alfa subcutaneously to maintain or achieve hemoglobin (Hgb) level targets of 12.0 to 14.0 g/dL (120 to 140 g/L). The control/delayed treatment group had Hgb levels of 9.0 +/- 0.5 g/dL (90 +/- 5 g/L) before therapy was started: target level was 9.0 to 10.5 g/dL (90 to 105 g/L). Optimal blood pressure and parathyroid hormone, calcium, and phosphate level targets were prescribed; all patients were iron replete. The primary end point is LV growth at 24 months.. One hundred fifty-two patients were eligible for the intention-to-treat analysis: mean age was 57 years, 30% were women, 38% had diabetes, and median glomerular filtration rate was 29 mL/min (0.48 mL/s; range, 12 to 55 mL/min [0.20 to 0.92 mL/s]). Blood pressure and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were similar in the control/delayed treatment and treatment groups at baseline. Erythropoietin therapy was administered to 77 of 78 patients in the treatment group, with a median final dose of 2,000 IU/wk. Sixteen patients in the control/delayed treatment group were administered erythropoietin at a median final dose of 3,000 IU/wk. There was no statistically significant difference between groups for the primary outcome of mean change in LV mass index (LVMI) from baseline to 24 months, which was 5.21 +/- 30.3 g/m2 in the control/delayed treatment group versus 0.37 +/- 25.0 g/m2 in the treatment group. Absolute mean difference between groups was 4.85 g/m2 (95% confidence interval, -4.0 to 13.7; P = 0.28). Mean Hgb level was greater in the treatment group throughout the study and at study end was 12.75 g/dL (127.5 g/L in treatment group versus 11.46 g/dL [114.6 g/L] in control/delayed treatment group; P = 0.0001). LV growth occurred in 20.1% in the treatment group versus 31% in the control/delayed treatment group (P = 0.136). In patients with a stable Hgb level, mean LVMI did not change (-0.25 +/- 26.7 g/m2), but it increased in those with decreasing Hgb levels (19.3 +/- 28.2 g/m2; P = 0.002).. This trial describes disparity between observational and randomized controlled trial data: observed and randomly assigned Hgb level and LVMI are not linked; thus, there is strong evidence that the association between Hgb level and LVMI likely is not causal. Large randomized controlled trials with unselected patients, using morbidity and mortality as outcomes, are needed.

Topics: Adult; Aged; Anemia; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium; Canada; Chronic Disease; Epoetin Alfa; Erythropoietin; Female; Heart Failure; Heart Ventricles; Hemoglobins; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases; Lipids; Male; Middle Aged; Organ Size; Parathyroid Hormone; Phosphates; Recombinant Proteins; Renal Dialysis; Single-Blind Method; Treatment Failure; Ultrasonography

Cardiovascular disease is the major cause of mortality in maintenance hemodialysis patients. Left ventricular dysfunction is present in approximately 80% of these patients and is highly predictive of future ischemic heart disease, cardiac failure, and death. Anemia has been identified as one of several risk factors responsible for cardiac complications. The treatment of renal anemia with recombinant human erythropoietin (rHuEpo) and consequent improvement of cardiac performance may reverse pathological changes in left ventricular geometry. In this study, the acute and chronic effects of rHuEpo administration on 24-hour ambulatory blood pressure recordings and echocardiographic parameters in 30 rHuEpo-naïve maintenance hemodialysis patients were examined. Twenty-four-hour ambulatory blood pressure monitoring was performed prior to and after 1 week and 6 months of rHuEpo administration. The patients underwent echocardiographic examination prior to and after 6 months of rHuEpo administration. One week treatment with rHuEpo did not cause any significant change in 24-hour ambulatory blood pressure recordings. After 6 months of therapy, serum hemoglobin levels increased from 8.8 +/- 0.66 g/dL to 10.8 +/- 0.70 g/dL (P < 0.05). Echocardiographic examination revealed elevation in ejection fraction (62.26 +/- 6.84% vs. 69.90 +/- 8.98%, P < 0.05) with reductions in fractional shortening (36.70 +/- 4.96% vs. 35.96 +/- 6.32%, P < 0.05), interventricular septum thickness (1.21 +/- 0.16 vs. 1.00 +/- 0.16 cm, P < 0.05), and left ventricular mass index (148.2 +/- 46.5 g/m2 vs. 93.6 +/- 17.2 g/m2, P < 0.05). Doppler echocardiography and tissue Doppler imaging provided additional information in comparison with conventional echocardiography. Before treatment, mitral flow E wave (E, 0.64 +/- 0.27 vs. 0.82 +/- 0.17 cm/s), mitral flow A wave (A, 0.80 +/- 0.21 vs. 0.70 +/- 0.21 cm/s), early diastolic velocity of lateral wall (Lateral E', 11.2 +/- 2.8 vs. 12.4 +/- 2.3 cm/s), late diastolic velocity of lateral wall (Lateral A', 6.7 +/- 2.5 vs. 7.8 +/- 2.1 cm/s), early diastolic velocity of septal wall (Septal E', 9.7 +/- 2.9 vs. 11.3 +/- 1.1 cm/s), and late diastolic velocity of septal wall (Septal A', 6.4 +/- 2.1 vs. 7.8 +/- 2.0 cm/s) were significantly lower in patients than in the controls. Patients and controls have similar deceleration time of mitral flow E wave (E Dec, 186 +/- 57.8 vs. 192 +/- 62.4 ms), isovolumic left ventricular relaxation time (IVRT, 111.9 +/- 30.7 vs. 91

Topics: Anemia; Blood Flow Velocity; Blood Pressure Monitoring, Ambulatory; Diastole; Echocardiography; Erythropoietin; Female; Heart Septum; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Stroke Volume; Systole

It is not known whether prevention of anemia among patients with chronic kidney disease would affect the development or progression of left ventricular (LV) hypertrophy. A randomized controlled trial was performed with 155 patients with chronic kidney disease (creatinine clearance, 15 to 50 ml/min), with entry hemoglobin concentrations ([Hb]) of 110 to 120 g/L (female patients) or 110 to 130 g/L (male patients). Patients were monitored for 2 yr or until they required dialysis; the patients were randomized to receive epoetin alpha as necessary to maintain [Hb] between 120 and 130 g/L (group A) or between 90 and 100 g/L (group B). [Hb] increased for group A (from 112 +/- 9 to 121 +/- 14 g/L, mean +/- SD) and decreased for group B (from 112 +/- 8 to 108 +/- 13 g/L) (P < 0.001, group A versus group B). On an intent-to-treat analysis, the changes in LV mass index for the groups during the 2-yr period were not significantly different (2.5 +/- 20 g/m(2) for group A versus 4.5 +/- 20 g/m(2) for group B, P = NS). There was no significant difference between the groups in 2-yr mean unadjusted systolic BP (141 +/- 14 versus 138 +/- 13 mmHg) or diastolic BP (80 +/- 6 versus 79 +/- 7 mmHg). The decline in renal function in 2 yr, as assessed with nuclear estimations of GFR, also did not differ significantly between the groups (8 +/- 9 versus 6 +/- 8 ml/min per 1.73 m(2)). In conclusion, maintenance of [Hb] above 120 g/L, compared with 90 to 100 g/L, had similar effects on the LV mass index and did not clearly affect the development or progression of LV hypertrophy. The maintenance of [Hb] above 100 g/L for many patients in group B might have been attributable to the relative preservation of renal function.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Time Factors

Renal anemia is an important determinant for left ventricular hypertrophy in dialysis patients and an independent prognosis parameter for the cardiovascular survival in dialysis patients. In addition, an autonomic dysfunction is associated with the uremic state and influences the cardiovascular risk in patients with end-stage renal disease (ESRD).. We investigated in this prospective longitudinal study the effect of hemoglobin normalization by a chronic treatment with recombinant human erythropoietin (rhEPO) on cardiovascular prognosis parameters in 23 patients on chronic hemodialysis with renal anemia (hemoglobin concentration < or =10.5 g/dL) and echocardiographically proven left ventricular hypertrophy. We studied muscle sympathetic nerve activity measured by microneurography; cardiopulmonary baroreflex activity by lower-body negative pressure (LBNP-) testing; left ventricular structure and mass index (LVMI) by echocardiography; blood pressure by 24-hour readings; peripheral blood flow and vascular resistance by plethysmography before (U1) and after 7 months of chronic rhEPO treatment (U2).. In the anemic state, mean (+/- SD) muscle sympathetic nerve activity in ESRD was elevated (U1 rest, 34 +/- 13 bursts per minute) and cardiopulmonary baroreflex response during LBNP markedly lacking (U1 -15 mm Hg, 34 +/- 13 bursts per minute) reflecting a severely impaired autonomic function. Normalization of the hemoglobin concentration by chronic rhEPO treatment (U1, 10.5 +/- 0.9 g/dL versus U2, 13.4 +/- 3.1 g/dL, P <0.001) did not influence sympathetic nerve activity (U2, 34 +/- 15 bursts per minute, NS) and cardiopulmonary baroreflex sensitivity did not change (U2 -15 mm Hg, 37 +/- 16 bursts per minute, NS). LVMI decreased significantly after chronic treatment with rhEPO (U1, 134 +/- 26 g/m2 versus U2, 97 +/- 25 g/m2, P < 0.001) and left ventricular geometry developed from an asymmetric to a symmetric configuration (U1, relative wall thickness 0.58 versus U2, 0.43, P < 0.001). Under treatment with rhEPO, 24-hour systolic and diastolic blood pressure did not increase (systolic U1, 132 +/- 4 mm Hg versus U2, 128 +/- 3 mm Hg, NS, and diastolic U1, 76 +/- 2 mm Hg versus U2, 73 +/- 2 mm Hg, NS). Peripheral blood flow (U1, 6.1 +/- 3.3 mL/100 mL/min versus U2, 6.2 +/- 0.6 mL/100 mL/min, NS) as well as forearm vascular resistance (U1, 15.7 +/- 3.3 mm Hg/mL/100 mL versus U2, 14.9 +/- 3.1 mm Hg/mL/100 mL, NS) did not change by chronic rhEPO treatment.. Normalization of hemoglobin by chronic rhEPO treatment in dialysis patients has beneficial cardiovascular effects with regression of left ventricular hypertrophy and improvement of left ventricular geometry. However, a reduction of sympathetic overactivity or a resetting of baroreceptor sensitivity by a rhEPO treatment in dialysis patients in the medium-term could not be demonstrated. The reason for this may be the complex and multifactorial pathomechanism of autonomic dysfunction and cardiovascular disease in ESRD.

Topics: Adult; Aged; Anemia; Baroreflex; Blood Pressure; Echocardiography; Erythropoietin; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Longitudinal Studies; Male; Middle Aged; Prognosis; Prospective Studies; Recombinant Proteins; Regional Blood Flow; Renal Dialysis

Renal anaemia is an independent risk factor for the development of left ventricular hypertrophy (LVH), heart failure and mortality. Studies show that partial correction of anaemia leads to partial regression of LVH. However, early initiation of anaemia therapy may be the optimal way to reduce cardiac morbidity and mortality. The Cardiovascular risk Reduction by Early Anemia Treatment with Epoetin Beta (CREATE) trial will investigate the effect of early anaemia correction on cardiovascular risk reduction in patients not yet on renal replacement therapy. The primary objectives of this open, randomized, multicentre trial are to investigate the effect of early anaemia correction on the change in left ventricular mass index after 1 year, and the time to first cardiovascular event. The trial comprises two treatment arms: early intervention where patients will receive epoetin beta when their haemoglobin (Hb) level is 11-12.5 g/dl and their target Hb will be 13-15 g/dl, and late intervention, where patients will receive epoetin beta once their Hb level is <10.5 g/dl and their target Hb will be 10.5-11.5 g/dl. The study will be event-driven with a continuous evaluation and an interim analysis once every year. The inclusion of 600 patients is based on assumption of a 15-20% event rate in the control group and that 200 events are needed to detect a reduction of about one-third. In conclusion, the CREATE trial will examine whether early anaemia treatment will prevent development of LVH, reduce cardiovascular morbidity and provide other benefits.

Topics: Anemia; Cardiovascular Diseases; Erythropoietin; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Recombinant Proteins; Risk Factors

The optimal target hematocrit (Ht) level in recombinant human erythropoietin (rHuEPO) therapy remains controversial and has hardly been investigated in predialysis patients. We prospectively studied the regression of left ventricular hypertrophy (LVH) on echocardiography in nine predialysis patients with chronic renal failure after a partial correction (target Ht, 30%) and normalization (target Ht, 40%) of the Ht with rHuEPO treatment. Twenty-four-hour ambulatory blood pressure monitoring was also performed. The administration of rHuEPO significantly increased Ht to the target values. The rate of renal failure progression did not change during rHuEPO treatment for 12 months (Cr, from 6.2 +/- 2.0 to 5.5 +/- 2.1 mg/dL). The left ventricular mass index (LVMI) tended to decrease after a partial correction of anemia (Ht, 32.1% +/- 1.8%) at 4 months, whereas it tended to significantly decrease after normalization of Ht (Ht, 39.1% +/- 2.4%) at 12 months (baseline, 140.6 +/- 12.1 g/m2; partial correction, 126.9 +/- 10.0 g/m2; normalization, 111.2 +/- 8.3 g/m2). All patients had received antihypertensive medication before rHuEPO administration, and additional drugs were also required in four cases during the study. As a result, a good overall blood pressure control was obtained without any adverse effects on the circadian blood pressure rhythm. In conclusion, from the perspective of LVH regression, the normalization of Ht was found to be more effective than that associated with a partial correction of anemia during rHuEPO therapy.

Topics: Aged; Disease Progression; Erythropoietin; Female; Hematocrit; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

Hemoglobin levels below 10 g/dL lead to left ventricular (LV) hypertrophy, LV dilation, a lower quality of life, higher cardiac morbidity, and a higher mortality rate in end-stage renal disease. The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown.. One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were randomly assigned to receive doses of epoetin alpha designed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks. The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation.. In patients with concentric LV hypertrophy, the changes in LV mass index were similar in the normal and low target hemoglobin groups. The changes in cavity volume index were similar in both targets in the LV dilation group. Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved (8 mL/m2 per 1 g/dL hemoglobin decrement, P = 0.009). Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation. Normalization of hemoglobin led to improvements in fatigue (P = 0.009), depression (P = 0.02), and relationships (P = 0.004).. Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation. It may, however, prevent the development of LV dilation, and it leads to improved quality of life.

Topics: Adult; Aged; Anemia; Cardiac Volume; Cardiomyopathy, Dilated; Echocardiography; Erythropoietin; Female; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Ischemia; Patient Satisfaction; Quality of Life; Renal Dialysis; Surveys and Questionnaires; Thrombosis

In a two-way study, we treated renal anemia in chronic hemodialysis patients with recombinant human erythropoietin (rh-EPO) and followed heart morphology and function dynamics by echocardiography. Thirty-eight patients were randomly divided in two equal groups: the therapy group, treated with rh-EPO for 24 months, and the control group, not treated during the first 12 months and treated with rh-EPO during the second 12 months. Anemia was corrected, and hematocrit was maintained between 30 and 35 vol% by subcutaneous rh-EPO administration. Echocardiographic assessment was performed at the end of the untreated control phase and was repeated after 12 months of rh-EPO treatment in the control group and after 12 and 24 months of treatment in the therapy group. The results revealed significant morphologic, hemodynamic, and eventually functional changes. After 12 months of rh-EPO treatment, the end-diastolic volume (EDV) decreased from 135.8 +/- 23.7 to 109.8 +/- 25.3 ml, p < 0.001; stroke volume (SV) from 91.9 +/- 17.6 to 71.3 +/- 12.4 ml, p < 0.001; left ventricular mass-Devereux (LVMD) from 297.2 +/- 57.8 to 218.0 +/- 50.4 g, p < 0.01; cardiac output (CO) from 7,279 +/- 1,932 to 5,711 +/- 1,276 ml/min, p < 0.002; total peripheral resistance (TPR) rose from 1,330 +/- 390 to 1,707 +/- 373 dynes x s/cm5, p < 0.007. After 24 months, LVMD decreased further from 224.6 +/- 43.1 to 195.7 +/- 46.3 g, p < 0.004. The relaxation time index (RTI) decreased from 64.7 +/- 20.4 to 52.4 +/- 18.0 ms, p < 0.045, suggesting improved diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Anemia; Echocardiography; Erythropoietin; Female; Heart; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

Children with end stage renal failure and anaemia have an increased cardiac index and often gross ventricular hypertrophy. The contribution of anaemia to these abnormalities is uncertain. Eleven children with end stage renal failure and anaemia (haemoglobin concentration < 90 g/l) were enrolled into a single blind, placebo controlled, crossover study to assess the cardiovascular effects of reversing anaemia using subcutaneous human recombinant erythropoietin (r-HuEpo). Each limb lasted 24 weeks; seven children completed both limbs of the study. Haemoglobin increased with r-HuEpo, remaining above 100 g/l for a mean of 11 weeks. Cardiac index fell as a result of a reduction in both left ventricular stroke volume and heart rate. Left ventricular end diastolic diameter also decreased. In five children left ventricular wall thickness and left ventricular mass decreased with r-HuEpo, but this failed to reach significance for the whole group. Blood pressure did not change in six normotensive children completing an r-HuEpo limb; the decrease in cardiac index was therefore balanced by an increase in peripheral vascular resistance. Three children were taking anti-hypertensive treatment at the start of the study; one required an increase, and one a decrease, in treatment during the r-HuEpo limb. Short term treatment with r-HuEpo reduces cardiac index. A longer study is needed to determine whether this will, in time, result in a significant reduction in left ventricular hypertrophy.

Topics: Anemia; Blood Pressure; Cardiac Output; Child; Child, Preschool; Echocardiography; Electrocardiography; Erythropoietin; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Single-Blind Method; Stroke Volume; Ventricular Function, Left

Anemia in patients with chronic kidney disease (p-CKDs) may initiate or exacerbate left ventricular hypertrophy (LVH). This study aimed to determine whether treatment using long-acting erythropoietin-stimulating agents (L-ESAs) is independently associated with LVH during the pre-dialysis to maintenance dialysis period in p-CKDs.. Physical and laboratory examinations were performed 120 days before initiating dialysis in p-CKDs (baseline). To evaluate the left ventricular mass index (LVMI) after starting dialysis, the mean hemoglobin (Hb) was defined as the average at the start of dialysis and 6 months after starting dialysis. Changes in the LVMI were observed in three groups according to mean Hb levels (Hb < 10.1, 10.1 < Hb < 11.0, and Hb > 11.0 g/dL for Groups 1, 2, and 3, respectively). LVMI was evaluated using echocardiography at the pre-dialysis, initiation, and maintenance dialysis periods.. A lower LVMI at dialysis initiation and an improvement in LVMI were detected in the highest tertile group of mean Hb (11.0 g/dl). Consequently, in the high Hb group (Hb level > 11.0 g/dl), LVMI remained low from dialysis initiation until after 6 months.The relationship between Hb and LVMI was not significant; however, a constant correlation with β ≥ 0.4 in the absolute value was maintained.. L-ESAs may correlate with Hb and LVMI after administration, independent of the baseline LVMI and Hb values. These findings have therapeutic implications in the treatment strategies for p-CKDs during the pre-dialysis to maintenance dialysis period.

Topics: Anemia; Dialysis; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Longitudinal Studies; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies

This study investigated whether administering erythropoiesis-stimulating agents (ESAs) improves endothelial function in patients with non-dialysis chronic kidney disease (CKD) and anemia.. This single-center, prospective, single-arm comparison study enrolled patients with non-dialysis CKD (stages 4-5) and hemoglobin levels <10 g/dL. ESA administration followed the Kidney Disease: Improving Global Outcomes guideline. The primary endpoint was the change in flow-mediated dilatation after ESA administration in individual patients. The secondary endpoints were changes in 6-minute walk test results, blood pressure, New York Heart Association class, and echocardiographic parameters. The echocardiographic parameters examined included chamber quantification, Doppler parameters, and systolic and diastolic function parameters.. Initially, 13 patients were screened, but 2 discontinued due to either heart failure or voluntary withdrawal. The mean flow-mediated dilatation values significantly increased by 10.59% (from 1.36% ± 1.91% to 11.95% ± 8.11%, P = .001). Echocardiographic findings showed that the left ventricular mass index decreased by 11.9 g/m2 (from 105.8 ± 16.3 to 93.9 ± 19.5 g/m2, P  =  .006), and the left atrial volume index decreased by 10.8 mL/m2 (from 50.1 ± 11.3 to 39.3 ± 11.3 mL/m2, P = .004) after 12 weeks of ESA administration. There were no significant differences between pre- and post-ESA treatment 6-minute walk test results. No significant side effects were observed during the study period.. This is the first clinical study to demonstrate that an ESA improves endothelial dysfunction, left ventricular hypertrophy, and left atrial volume in patients with non-dialysis CKD. Thus, ESAs may be considered as adjunctive therapy for reducing cardiovascular risk in these patients.

Topics: Aged; Anemia; Blood Pressure; Comorbidity; Echocardiography; Endothelium, Vascular; Erythropoietin; Female; Glomerular Filtration Rate; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Polyethylene Glycols; Prospective Studies; Renal Insufficiency, Chronic; Severity of Illness Index; Walk Test

The response to erythropoietin (EPO) treatment varies considerably in individual patients on chronic hemodialysis. The EPO resistance index (ERI) has been considered useful to assess the EPO resistance and can be easily calculated in the clinic. The aim of this study was to investigate the association between ERI and left ventricular mass (LVM) and function and to determine whether ERI was associated with cardiovascular events in patients on hemodialysis. This study was designed prospectively. Clinical, laboratory, and echocardiographic variables were assessed in 72 patients on hemodialysis. The ERI was determined as the weekly weight-adjusted dose of EPO (U/kg/week) divided by hemoglobin concentration (g/dL). Patients were divided into three groups by tertiles of ERI. Patients with higher tertiles of ERI had a higher LVM index and lower LV ejection fraction compared with those with lower tertiles of ERI (P = 0.019 and P = 0.030, respectively). The median follow-up period was 53 months. The Kaplan-Meier plot showed increased frequency of cardiovascular events in patients with higher tertiles of ERI, compared with those with lower tertiles of ERI (P = 0.011, log-rank test). The multivariate Cox proportional hazard models showed that the ERI was the significant independent predictor of cardiovascular events (HR 3.00, 95% CI, 1.04-8.62, P = 0.042). Our data show that ERI was related with LVM index, LV systolic function and cardiovascular events in patients with hemodialysis. By monitoring of ERI, early identification of the EPO resistance may be helpful to predict the cardiovascular risk in hemodialysis patients.

Topics: Drug Resistance; Echocardiography; Erythropoietin; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

Oxidative stress (OS) is involved in left ventricular hypertrophy (LVH). Short-term treatment with erythropoietin (EPO) in chronic kidney disease (CKD) complicated by anemia and LVH is associated with a reduction in left ventricular mass (LVM). We proposed to assess whether the pro-oxidant status of CKD influences these outcomes.. Predialysis patients (n = 76) with CKD and hemoglobin (Hb) levels < 11 g/dl received EPO for 6 months. The effects of this anemia correction on LVH regression were evaluated using echocardiography. Patients with LVM decrease > 10% were considered "responders" (n = 25) to treatment and those with LVM change < 10% were considered "non-responders" (n = 24). Measurement of OS included plasma and erythrocyte oxidized (GSSG) and reduced (GSH) glutathione, GSH redox ratio (GSSG/GSH), erythrocyte glutathione peroxidase (GPx) and oxidized LDL (Ox- LDL).. 49 patients completed the study. With EPO therapy, mean Hb levels increased from 9.9 ± 0.6 to 12.8 ± 1.5 g/ dl (p < 0.0001) and LVM index decreased from 69.2 ± 17.7 to 64.1 ± 19.6 g/m2.7 (p = 0.01). At 6 months, "non-responders" had higher systolic blood pressure, pulse pressure, GSSG and GSH redox ratio and lower GSH than "responders". In multivariate analysis, and following adjustment for confounding variables, systolic blood pressure and GSH redox ratio independently predicted LVH regression.. Blood pressure and plasma GSH redox ratio (a marker of OS) are important predictors of LVH regression in anemic predialysis patients treated with EPO.

Topics: Aged; Anemia; Biomarkers; Blood Pressure; Chi-Square Distribution; Chronic Disease; Erythropoietin; Female; Glutathione; Glutathione Disulfide; Glutathione Peroxidase; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Lipoproteins, LDL; Logistic Models; Male; Middle Aged; Multivariate Analysis; Oxidative Stress; Recombinant Proteins; Time Factors; Treatment Outcome; Ultrasonography

Recent studies revealed that erythropoietin (EPO) has tissue-protective effects in the heart by increasing vascular endothelial growth factor (VEGF) expression and attenuating myocardial fibrosis in ischemia models. In this study, we investigated the effect of EPO on ventricular remodeling and blood vessel growth in diabetic rats.. Male SD rats were randomly divided into 3 groups: control rats, streptozotocin (STZ)-induced diabetic rats, and diabetic rats treated with 1000 U/kg EPO by subcutaneous injection once per week. Twelve weeks later, echocardiography was conducted, and blood samples were collected for counting of peripheral blood endothelial progenitor cells (EPCs). Myocardial tissues were collected, quantitative real-time PCR (RT-PCR) was used to detect the mRNA expression of VEGF and EPO-receptor (EPOR), and Western blotting was used to detect the protein expression of VEGF and EPOR. VEGF, EPOR, transforming growth factor beta (TGF-β), and CD31 levels in the myocardium were determined by immunohistochemistry. To detect cardiac hypertrophy, immunohistochemistry of collagen type I, collagen type III, and Picrosirius Red staining were performed, and cardiomyocyte cross-sectional area was measured.. After 12 weeks STZ injection, blood glucose increased significantly and remained consistently elevated. EPO treatment significantly improved cardiac contractility and reduced diastolic dysfunction. Rats receiving the EPO injection showed a significant increase in circulating EPCs (27.85 ± 3.43%, P < 0.01) compared with diabetic untreated animals. EPO injection significantly increased capillary density as well as EPOR and VEGF expression in left ventricular myocardial tissue from diabetic rats. Moreover, EPO inhibited interstitial collagen deposition and reduced TGF-β expression.. Treatment with EPO protects cardiac tissue in diabetic animals by increasing VEGF and EPOR expression levels, leading to improved revascularization and the inhibition of cardiac fibrosis.

Topics: Animals; Blotting, Western; Collagen Type I; Collagen Type III; Diabetes Mellitus, Experimental; Endothelial Cells; Erythropoietin; Fibrosis; Gene Expression Regulation; Hypertrophy, Left Ventricular; Immunohistochemistry; Injections, Subcutaneous; Male; Myocardial Contraction; Myocardium; Neovascularization, Physiologic; Platelet Endothelial Cell Adhesion Molecule-1; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Receptors, Erythropoietin; Recovery of Function; RNA, Messenger; Stem Cells; Time Factors; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

To ascertain mechanisms of development of left ventricular hypertrophy (LVH) and possible cardioprotective action of anemia correction in patients with end-stage renal disease.. A total of 98 patients (53 females and 45 males aged 49.4 +/- 14 years) on hemodialysis participated in the study. The patients were examined clinically with estimation of the levels of parathormone, calcium, phosphorus, erythrocytic indices, serum ferritin, blood transferrin. Echocardiography with dopplerography on Aloka-4000 unit were made. Left ventricular geometry was assessed by J. Gottdiener classification. Therapeutic policy aimed at correction of anemia, arterial hypertension, phosphorus-calcium metabolism.. The patients were treated and followed up for 18 months. The examination was done before treatment, 12 and 18 months later. After the trial the patients were divided into 4 groups depending on the results obtained on LVH development. Blood pressure, hemoglobin, echocardiographic parameters changed according to the patient's group. After 18 months of observation and treatment with erythropoietin and iron preparations, ACE inhibitors, angiotensin II receptor blockers, beta-adrenoblockers, drugs regulating phosphorus-calcium metabolism some cases were seen of reduction of systolic blood pressure, achievement of target hemoglobin level, regression of LVH.. Combined treatment of hemodialysis patients including antianemic, antihypertensive drugs promoted improvement of LVH or its regression in some cases.

Topics: Adrenergic beta-Antagonists; Adult; Anemia; Angiotensin-Converting Enzyme Inhibitors; Combined Modality Therapy; Erythropoietin; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Vitamin D deficiency is highly prevalent in chronic kidney disease. The aim of this study was to evaluate the effects of oral cholecalciferol supplementation on mineral metabolism, inflammation, and cardiac dimension parameters in long-term hemodialysis (HD) patients.. This 1-year prospective study included 158 HD patients. Serum levels of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], intact parathyroid hormone, and plasma brain natriuretic peptide as well as circulating bone metabolism and inflammation parameters were measured before and after supplementation. Baseline 25(OH)D and 1,25(OH)(2)D levels were measured twice (end of winter and of summer, respectively). Therapy with paricalcitol, sevelamer, and darbepoietin was evaluated.. There was an increase in serum 25(OH)D and 1,25(OH)(2)D levels after supplementation. Conversely, serum calcium, phosphorus, and intact parathyroid hormone were decreased. There was a reduction in the dosage and in the number of patients who were treated with paricalcitol and sevelamer. Darbepoietin use was also reduced, with no modification of hemoglobin values. Serum albumin increased and C-reactive protein decreased during the study. Brain natriuretic peptide levels and left ventricular mass index were significantly reduced at the end of the supplementation.. Oral cholecalciferol supplementation in HD patients seems to be an easy and cost-effective therapeutic measure. It allows reduction of vitamin D deficiency, better control of mineral metabolism with less use of active vitamin D, attenuation of inflammation, reduced dosing of erythropoiesis-stimulating agents, and possibly improvement of cardiac dysfunction.

Topics: Administration, Oral; Aged; Biomarkers; Bone Density Conservation Agents; Bone Remodeling; C-Reactive Protein; Calcitriol; Calcium; Chelating Agents; Cholecalciferol; Chronic Disease; Darbepoetin alfa; Dietary Supplements; Ergocalciferols; Erythropoietin; Female; Hematinics; Humans; Hypertrophy, Left Ventricular; Inflammation Mediators; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Parathyroid Hormone; Phosphorus; Polyamines; Prospective Studies; Renal Dialysis; Serum Albumin; Sevelamer; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Vitamins

Anemia is common in patients with chronic heart failure and an independent predictor of poor prognosis. Chronic anemia leads to left ventricular (LV) hypertrophy and heart failure, but its molecular mechanisms remain largely unknown. We investigated the mechanisms, including the molecular signaling pathway, of cardiac remodeling induced by iron deficiency anemia (IDA). Weanling Sprague-Dawley rats were fed an iron-deficient diet for 20 wk to induce IDA, and the molecular mechanisms of cardiac remodeling were evaluated. The iron-deficient diet initially induced severe anemia, which resulted in LV hypertrophy and dilation with preserved systolic function associated with increased serum erythropoietin (Epo) concentration. Cardiac STAT3 phosphorylation and VEGF gene expression increased by 12 wk of IDA, causing angiogenesis in the heart. Thereafter, sustained IDA induced upregulation of cardiac hypoxia inducible factor-1alpha gene expression and maintained upregulation of cardiac VEGF gene expression and cardiac angiogenesis; however, sustained IDA promoted cardiac fibrosis and lung congestion, with decreased serum Epo concentration and cardiac STAT3 phosphorylation after 20 wk of IDA compared with 12 wk. Upregulation of serum Epo concentration and cardiac STAT3 phosphorylation is associated with a beneficial adaptive mechanism of anemia-induced cardiac hypertrophy, and later decreased levels of these molecules may be critical for the transition from adaptive cardiac hypertrophy to cardiac dysfunction in long-term anemia. Understanding the mechanism of cardiac maladaptation to anemia may lead to a new strategy for treatment of chronic heart failure with anemia.

Topics: Adaptation, Physiological; Anemia, Iron-Deficiency; Animals; Blood Pressure; Body Weight; Disease Models, Animal; Erythropoietin; Heart; Heart Failure; Heart Rate; Hypertrophy, Left Ventricular; Hypoxia-Inducible Factor 1, alpha Subunit; Iron; Kidney; Male; Myocardial Contraction; Myocardium; Neovascularization, Physiologic; Phosphorylation; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Receptors, Erythropoietin; STAT3 Transcription Factor; Time Factors; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Ventricular Function, Left; Ventricular Pressure; Ventricular Remodeling

Topics: Adaptation, Physiological; Anemia, Iron-Deficiency; Animals; Erythropoietin; Heart Failure; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Myocardial Contraction; Myocardium; Neovascularization, Physiologic; Phosphorylation; Receptors, Erythropoietin; STAT3 Transcription Factor; Time Factors; Ventricular Function, Left; Ventricular Remodeling

We report our experience of the first use of nocturnal home haemodialysis in Hong Kong. The patient, a 40-year-old man with end-stage renal failure, was recruited into the Nocturnal Home Haemodialysis Programme at Princess Margaret Hospital in 2006. He received haemodialysis at home on alternate nights (3.5 sessions per week) for 5.5 to 6 hours per session. After 1 year of nocturnal home haemodialysis, his recombinant human erythropoietin requirement had been reduced by more than 50%. His serum phosphate level decreased by 35% and calcium phosphate product by 34%. After nocturnal home haemodialysis, his blood pressure control has been excellent and he was able to cease taking anti-hypertensive medications soon after commencing nocturnal home haemodialysis. Regression of his left ventricular hypertrophy has also been noted, with a 39% decrease in his left ventricular mass index. The haemodialysis adequacy index, weekly single-pool Kt/V, increased by 59% after switching to nocturnal home haemodialysis and his quality-of-life indices also showed significant improvement. Nocturnal home haemodialysis holds promise as an alternative dialytic therapy for patients on chronic haemodialysis in Hong Kong.

Topics: Adult; Erythropoietin; Hemodialysis, Home; Hong Kong; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Quality of Life; Recombinant Proteins

Topics: Anemia; Cardiovascular Diseases; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Recombinant Proteins; Renal Insufficiency, Chronic

Anemia is common in end-stage renal disease (ESRD) patients and an important determinant for left ventricular hypertrophy (LVH) in dialysis patients. There are increasing numbers of biosimilar epoetin-alfa entering Thailand.. To conduct a prospective trial to evaluate the efficacy and safety of a biosimilar epoetin-alfa (epoetin) (Espogen) in ESRD patients receiving chronic hemodialysis complicated by anemia and to address its impact on the left ventricular mass index (LVMI) and volume index (LVVI) in these patients.. Twenty-two hemodialysis (HD) subjects were recruited from Rajavithi and Huachiew Hospitals. Inclusion criteria were chronic HD, hemoglobin (Hb) < 10 g/dL without preceding treatment (epoetin or transfusion) for 1 month. Echocardiographic baselines were obtained Epoetin-alfa was initially given 4,000 IU subcutaneously twice a week and titrated biweekly to keep the Hb range of 11 to 12 g/dL (titration period 12 weeks). Treatment continued until the end of 24 weeks. Records were made for conventional blood tests, blood pressure, amount of drugs needed to control blood pressure, and adverse events. Echocardiogram was repeated (on observer blinding) at the completion of the present study.. After 24-week of epoetin therapy, the predialysis Hb level increased significantly from 8.0 +/- 1.3 g/dL to 11.0 +/- 1.1 g/dL (p < 0.001). The mean dose of epoetin at the present study entry was 143.6 +/- 87.8 IU/kg/ week. At the present study entry, LVH was present in 86.4% of the patients. At the completion of the present study, a decrease in LVMI was observed in 50% of the patients; however, the mean LVMI change was not significantly different. Notably, there were minimal but significant changes in LVEDD (52.8 +/- 7.0 vs. 50.1 +/- 6.9 mm, p < 0.05), LVVI (86.2 +/- 25.2 vs. 75.5 +/- 19.5 mL/m2, p < 0.05) and when subjects were partitioned into tertiles of baseline LVMI, the LVVI change was confined to the highest tertile (103.7 +/- 25.2 vs. 79.6 +/- 21.9 mL/ m2, p < 0.05). The aortic root diameter also significantly decreased despite some increase in blood pressures but without significant change in number of antihypertensive agents. No serious adverse event was observed during the present study period.. The efficacy of anemia treatment and safety of the biosimilar epoetin-alfa was demonstrated in hemodialysis patients. Significant regression of LVVI and some reduction in LVMI were shown in this 24-week prospective trial.

Topics: Adult; Aged; Anemia; Epoetin Alfa; Erythropoietin; Female; Health Status Indicators; Heart Ventricles; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Time Factors; Treatment Outcome; Ultrasonography

In hemodialysis patients, left ventricular hypertrophy (LVH) correlates with mortality. The reason for LVH in uremics is multifactorial. The primary objective of our study was to investigate the effects of a multi-interventional treatment strategy on LVH.. In 230 ambulatory patients, including patients with coronary artery disease, diabetes, diastolic and systolic dysfunction, we continued optimized cardiac therapy (beta-blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) with full anemia correction by intravenous epoetin-beta. The dose of epoetin-beta for maintaining target hemoglobin (Hb) was 68 +/- 23 IU/kg/week. Serial echocardiograms were recorded every 3-6 months. The mean observation period was 4.8 +/- 1.2 years.. Mean Hb at baseline was 11.2 +/- 2.0 versus 14.1 +/- 1.4 g/dl (p < 0.001) at study end. There was a significant reduction in left ventricular mass index (LVMI: 159 +/- 50.4 vs. 130.2 +/- 42.7 g/m(2); p < 0.001). In a subgroup of 2/3 of the patients, LVMI returned to normal (169 +/- 33 vs. 114 +/- 14 g/m2; p < 0.001).. Baseline LVMI (p < 0.001), Hb increase (p < 0.03), and triple cardiac therapy (p < 0.03) were significant and independent prognostic factors for a reduction in LVMI. The annual cardiovascular mortality was 5%. Even anemia correction from 12 to 14 g/dl results in further (p < 0.001) regression of LVMI.

Topics: Aged; Anemia; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Erythropoietin; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Uremia

Topics: Anemia; Cardiovascular Diseases; Epoetin Alfa; Erythropoietin; Heart Failure; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Recombinant Proteins; Renal Insufficiency, Chronic

Left ventricular hypertrophy (LVH) is an independent predictor of morbidity and mortality in dialysis patients. It remains unclear whether efforts to correct anemia in patients with mild-to-moderate chronic renal insufficiency (CRI) can reverse LVH. This prospective multi-center Chinese cohort study evaluates left ventricular mass index (LVMI) evolution in anemic CRI patients with or without recombinant human erythropoietin (rHuEPO) therapy.. Six centers enrolled 158 patients with serum creatinine from 147 to 400 micromol/L, and 86 of whom with hemoglobin (Hb) levels < 110 g/L received rHuEPO (Group A). Forty patients with comparable Hb levels (< 110 g/L) but did not receive rHuEPO (Group B) and those with Hb >/= 110 g/L (Group C, n = 32) were served as controls. Echocardiographic studies were performed to evaluate LVMI at baseline and every 3 months during a two-year period.. At baseline, the prevalence of LVH was 72.1% in Group A, 72.5% in Group B and 59.4% in Group C. LVMI was inversely correlated with Hb levels (r = -0.70, P < 0.01). There was no difference in age, gender, aetiology of renal failure, blood pressure (BP) and cardiovascular risk factors between the 3 groups. The administration of rHuEPO in Group A significantly increased Hb levels from (93.8 +/- 14.6) g/L to (111.2 +/- 10.3) g/L and decreased LVMI from (142.6 +/- 25.7) g/m(2) to (132.4 +/- 18.5) g/m(2). The prevalence of LVH decreased 16.3% after a partial correction of anemia at 24 months, whereas Hb levels in controls (Group B and Group C) tended to decrease and LVMI significantly increased compared with baseline. The prevalence of LVH was significantly increased in Group B and C after 24 months. The percentage of patients whose serum creatinine level doubled during the follow-up was 3.4% in Group A, 15.0% in Group B and 9.4% in Group C, the difference between Group A and Group B being significant (P < 0.05). In addition, good BP control was obtained without any adverse effects.. High prevalence of LVH was present in pre-dialysis CRI patients, which is associated with severity of anemia. Early treatment of anemia with rHuEPO can reverse LVH in CRI patients.

Topics: Adolescent; Adult; Anemia; Cohort Studies; Erythropoietin; Female; Follow-Up Studies; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins

Cardiovascular complications are the leading cause of mortality in patients with end-stage renal disease. Left ventricular hypertrophy (LVH) is recognized as an independent risk factor for cardiovascular morbidity and mortality. At the onset of dialysis, more than 70% of the patients with chronic kidney disease have echocardiographic evidence of LVH. Anemia, increased red cells filterability time (RCFT), and blood viscosity are known to induce LVH.. To evaluate, prospectively, the effects of erythropoietin (EPO) therapy for 20 weeks on RCFT and left ventricular mass (LVM).. Twenty uremic and anemic predialysis patients with creatinine clearance test below 35 mL/min were studied. RCFT test and three-dimensional echocardiography were performed at 0, 10, and 20 weeks.. EPO therapy for 20 weeks did not adversely affect renal function and did not significantly change the mean blood pressure. It significantly increased the hemoglobin and fibrinogen levels, and decreased RCFT and LVM (p < .01).. Although correction of anemia can contribute to regression of LVM, we speculate that an increasing number of cells with normalized viscoelastic properties and a direct effect of EPO on erythrocytes and myocardiocytes, through specific receptors, may also play an important role.

Topics: Aged; Anemia; Echocardiography, Three-Dimensional; Erythrocyte Deformability; Erythropoietin; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Prospective Studies; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Bias; Biomarkers; Chronic Disease; Epoetin Alfa; Erythropoietin; Goals; Hemoglobins; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Randomized Controlled Trials as Topic; Recombinant Proteins; Reference Values; Research Design; Treatment Outcome

Acute alveolar hypoxia causes pulmonary vasoconstriction that matches lung perfusion to ventilation to optimize gas exchange. Chronic alveolar hypoxia induces pulmonary hypertension, characterized by increased muscularization of the pulmonary vasculature and right ventricular hypertrophy. Elevated erythropoietin (EPO) plasma levels increase hematocrit and blood viscosity and may affect structure and function of the pulmonary circulation. To differentiate between the direct effects of hypoxia and those linked to a hypoxia-induced increase in EPO/hematocrit levels, we investigated the lung vasculature in transgenic mice constitutively over-expressing EPO (termed tg6) upon exposure to normoxia and chronic hypoxia. Despite increased hematocrit levels (approximately 0.86),tg6 mice kept in normoxia did not develop selective right ventricular hypertrophy. The portion of vessels with a diameter of 51-95 microm and >155 microm was increased whereas the portion of small vessels (30-50 microm) was decreased. Pulmonary vascular resistance and the strength of hypoxic vasoconstriction measured in isolated perfused lungs were decreased. Vasoconstrictions induced by the thromboxane mimetic U46619 tended to be reduced. After chronic hypoxia (FiO2 = 0.10, 21 days), vascular resistance and vasoconstrictor responses to acute hypoxia and U46619 were reduced in tg6 mice compared to wildtype controls. Chronic hypoxia increased the degree of pulmonary vascular muscularization in wildtype but not in tg6 mice that already exhibited less muscularization in normoxia. In conclusion, congenital over-expression of EPO exerts an "anti-pulmonary hypertensive" effect, both structurally and functionally, particularly obvious upon chronic hypoxia.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Aspirin; Blood Pressure; Blood Vessels; Blood Viscosity; Cyclooxygenase Inhibitors; Erythropoietin; Hematocrit; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Hypertrophy, Right Ventricular; Hypoxia; Lung; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle, Smooth, Vascular; Nitric Oxide Synthase; omega-N-Methylarginine; Up-Regulation; Vascular Resistance; Vasoconstriction; Vasoconstrictor Agents

Left ventricular hypertrophy (LVH) is commonly present in hemodialysis patients (HD pts) and is considered as an independent risk factor for high mortality. Many studies have confirmed sound connection between anemia and LVH in this patients.. To analyse dystolic function of LVH in uraemic pts during the 6 months human recombinant erythropoectin (rHu-Epo) treatment of anemia, with emphasis on the role of nitric oxide (NO), whose role in regulation of LV diastolic distensibility has been hinted in some recent studies.. The study included 20 HD pts, aged 39.6 +/- 5.3 yrs, with the same condition of HD treatment, signs of anemia and echocardiographically verified LVH. Pulse Doppler echocardiography confirmed LV diastolic function as a ratio of early to late diastolic mitral flow velocity (E/A). Nitrate concentration was determined by colorimetric method using Greiss reagent. Renal anemia was treated with rHuEpo.. Six months rHuEpo treatment of anemia in HD pts with LVH caused significant reduction of LV mass index (p = 0.008). However, we observed unfavourable fall in LV diastolic function (E/A = 0.83, p = 0.007). In the same time, it was found that the serum NO level was higher for 11.8% in HD pts with LVH as compared with the pts with normal LV mass. Also, the significant positive correlation was found between the level of NO and LV mass index before (p = 0.004) and after rHuEpo therapy (p = 0.03), as well as a significant positive correlation between NO and E/A in the same conditions (p = 0.002) and p = 0.049). Level of NO negatively correlates with blood hemoglobin level, but without statistical significance.. Correction of anemia with rHuEpo leads to the significant partial regression of LVH. Reduction of diastolic function of LV, observed after diminished LV mass index, could be related to the significant fall of NO level and damaged response of LV to NO. The results of the study strongy suggest that NO can present an important determinant of LV diastolic function in uraemic pts.

Topics: Adult; Anemia; Diastole; Echocardiography, Doppler, Pulsed; Erythropoietin; Humans; Hypertrophy, Left Ventricular; Nitric Oxide; Recombinant Proteins; Renal Dialysis; Ventricular Function, Left

Hypertension and anemia may be causes of left ventricular hypertrophy (LVH) in uremia but the molecular mechanism is not known. Uremia was induced in male Spraugue Dawley rats by 5/6 nephrectomy. The following groups of rats were studied for 6 weeks; uremic rats (U) fed ad. lib., control rats (C) pair-fed with U, U rats given hydralazine (100 mg/kg/day) (UH), U rats given erythropoietin (48 U/kg/week, i.p.) (UE). Both diastolic and mean arterial pressures are higher (P < 0.01) in U and UE compared with C whereas both pressures in UH were normalized. Hemoglobin in U was lower than in C, and was normalized in UE. U, UH and UE had higher heart weight/body weight ratios (HW/BW) as well as left ventricular weight/body weight ratios (LV/BW) compared with C (P < 0.01). Compared with U, UH has lower HW/BW and LV/BW (P < 0.05) and UE has normal HW/BW but lower LV/BW than U (P < 0.05). To see if the gene expression in uremic LVH is similar to that described in pressure overload LVH in which mRNA levels of angiotensin converting enzyme (ACE), transforming growth factor-beta1 (TGF-beta1), atrial natriuretic factors (ANF) and skeletal a- actin were increased, we measured these mRNA levels by Northern analysis. TGF-beta1, ACE and alpha-actin mRNA levels were not changed in all 4 groups. ANF mRNA in U and UE was increased 3 fold over C, and normalized in UH. Treatment of anemia with erythropoietin improved uremic LVH but did not change ANF mRNA; whereas treatment of hypertension with hydralazine normalized ANF mRNA but did not completely correct uremic LVH. Thus, gene expression in uremic LVH is distinct from that in pressure-overload LVH, suggesting that other unidentified factor(s) might be involved in uremic LVH.

Topics: Actins; Anemia; Animals; Atrial Natriuretic Factor; Erythropoietin; Gene Expression; Heart Ventricles; Hydralazine; Hypertension; Hypertrophy, Left Ventricular; Male; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transforming Growth Factor beta; Transforming Growth Factor beta1; Uremia

Anemia has been shown to be a key component of renal failure, as well as of the occurrence of left ventricular hypertrophy (LVH), with special attention paid to the paracrine mechanism of left ventricular remodelling.. The aim of the study was to analyze possible association of serum angiotensin-converting enzyme (ACE) activity and LVH in hemodialysis patients with anemia treated with human recombinant erythropoietin (rHuEpo) during six months.. LV geometry was determined by echocardiographic analysis in 20 hemodialysis patients before and after erythropoietin treatment. Serum ACE activity was measured by spectrophotometric method using hippyril-l-histidyl-l-leucin as a substrate.. Serum ACE activity increased to 47.3% in hemodialysis patients with LVH as compared to patients with normal LV mass. A significant positive correlation was found between the level of ACE activity and LV mass index (p=0.004). Six-month erythropoietin treatment of anemia led to a significant reduction of LV mass index (p<0.008) and serum ACE activity (p=0.003) from the initial values.. The levels of serum ACE activity are associated with LV geometry. Our findings suggested the possibility of simultaneous and modest modulation of LV mass and serum ACE activity with rHuEpo correction of renal anemia.

Topics: Anemia; Erythropoietin; Humans; Hypertrophy, Left Ventricular; Peptidyl-Dipeptidase A; Recombinant Proteins; Renal Dialysis; Uremia

To investigate effects of early correction of anemia on the rate of cardiovascular complications and survival on regular hemodialysis (RHD).. Eighty patients with chronic renal failure (CRF) on regular hemodialysis entered two groups: group 1 with hemoglobin (Hb) < 80 g/l (n = 36) and group 2 with Hb > 100 g/l (n = 44). 90% patients of group 2 were treated for renal anemia for 6-8 months of predialysis CRF. When placed on RHD, group 1 started therapy with epoetin, 39 patients of group 2 continued epoetin treatment.. Patients of group 2 had a higher rate of eccentric left ventricular hypertrophy (LVH) with reduced ejection fraction and development of congestive cardiac failure and coronary heart disease. Eccentric LVH in group 1 patients regressed only in 80% when the patients were on hemodialysis and received epoetin for correction of anemia. Overall cardiac death in group 1 was twice that of group 2 patients.. Early correction of anemia led to a 50% increase in 5-year survival. This fact can be explained with inhibited progression of eccentric LVH.

Topics: Adult; Anemia; Cardiotonic Agents; Case-Control Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Ventricular Function, Left

Topics: Anemia, Hypochromic; Erythropoietin; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Recombinant Proteins; Ventricular Function, Left

The high cardiac output state is considered a major factor for occurrence of left ventricular hypertrophy (LVH). Increased left ventricular mass is a powerful predictor of morbidity and mortality. We analyzed morphologic changes of the heart in dialysis patients during treatment with erythropoietin (EPO) and after cessation of therapy. Fourteen hemodialysis patients were treated with EPO for 1 year. They were above age 18, dialyzed 3 times per week, and with a hematocrit below 28 vol%. EPO was given subcutaneously, at a dose of 20 U/kg body weight 3 times per week, before each hemodialysis session. Anemia was corrected and hematocrit maintained between 30 and 35 vol%. When this part of the study was completed, EPO was stopped in all 14 patients. Echocardiography was performed three times: at baseline, at 12 months of therapy, and 1 year after EPO cessation. Mean hematocrit of the group at these 3 time intervals was 23.78 +/- 2.11 vol%; 33.14 +/- 1.95 vol%; and 25.93 +/- 5.23 vol%, respectively (mean +/- SD). The following echocardiographic changes occurred. End-diastolic volume decreased from 134.8 +/- 25.4 to 113.2 +/- 26.4 ml and increased back to 136.2 +/- 46.2 ml. Left ventricular mass decreased from 296.6 +/- 62.4 to 225.2 +/- 52.7 g and increased again to 311.7 +/- 106 g. Cardiac output decreased from 7,295.8 +/- 2,166.9 to 5,816.4 +/- 1,216.2 ml/min and increased to 6,803.2 +/- 1,646.5 ml/min. Total peripheral resistance increased from 1,360.8 +/- 428 to 1,691.3 +/- 326 and decreased again to 1,242.8 +/- 303.3 dyne x s/cm5. All these changes were significant. Mean arterial pressure increased from 114.7 +/- 13.9 to 119.3 +/- 13.8 mm Hg and decreased to 100.5 +/- 9.3 mm Hg. LVH could be affected severely by the degree of anemia in uremics and was reversible.

Topics: Adult; Aged; Anemia; Cardiac Output; Erythropoietin; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Recurrence

15 years after recombinant erythropoietin (EPO) has become available for the treatment of renal anemia, the target hemoglobin concentration to be achieved is still controversial. A positive impact of partial correction of renal anemia on quality of life has been conclusively demonstrated. Several more recent studies indicate that further improvement of well-being can be achieved with normalization of hemoglobin levels. In addition, there is increasing evidence that anemia is associated with the progression of left-ventricular hypertrophy and mortality. These findings imply that correction of renal anemia has the potential to improve patient prognosis. However, in patients with advanced cardiac disease, the US normal hematocrit failed to demonstrate a prognostic benefit and instead suggested that the attempt to normalize hemoglobin may be harmful. Nevertheless, in patients with less advanced cardiac disease complete correction of renal anemia may prevent progressive ventricular dilatation. The impact of early anemia correction is currently tested in several trials in predialysis patients. Irrespective of the uncertainties about the upper target range, current US and European guidelines have defined a hemoglobin concentration of 11 g/dl as the lower target range on the basis of both symptomatic and prognostic considerations. In the majority of patients these minimum requirements are not yet achieved. Less then 10% of patients receive EPO prior to the onset of dialysis, the mean hemoglobin level at the start of dialysis is not higher than 9 g/dl and a significant proportion of patients permanently remain below 11 g/dl.

Topics: Aged; Anemia; Erythropoietin; Hemoglobins; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Renal Insufficiency

Dysfunction of the cardiovascular system is a common complication of chronic renal insufficiency. Many factors can cause left ventricular hypertrophy (LVH), and hypertension and anemia are among them. They play an important role in the pathogenesis of LVH as well as in the development of cardiac dysfunction. Echocardiography enables early detection of functional macrocirculatory changes as well as adequate measuring of cardiac structures and LV mass. Anemia of end-stage chronic renal insufficiency (ESRD) is only one among its many complications and has complex pathogenesis; one of the primary factors causing anemia is insufficient production of erythropoietin, a leading factor in the production of erythropoiesis. Anemia correction with recombinant human erythropoietin (r-HuEPO) in ESRD has a positive effect on the cardiovascular system. In this study the authors examined the hemodynamic effect of erythropoietin in anemic patients undergoing hemodialysis and observed its positive effect on the cardiovascular system. Twenty-two patients were included in the study (13 men and 9 women) mean age x=39.5 years. All patients were dialyzed three times a week for 4 hours and were all (Abstract continued) treated, according to protocol, with r-HuEPO for 8 months. Left ventricular mass was measured by the Penn Convention formula. The authors noticed the effectiveness of this therapy through an increase of hemoglobin of 35% and of hematocrit of 34% and a direct effect on the cardiovascular system. Echocardiographic findings showed decrease of LV mass from 391 to 274 mg (30%). The correction of renal anemia with erythropoietin leads to structural microcirculatory changes and partial morphologic regression of preexistent LVH, which again leads to regression of cardiac dysfunctions and improved hemodynamic effect, physical capacity, and cardiopulmonary status, and ultimately better quality of life for dialyzed patients.

Topics: Adult; Erythropoietin; Female; Hematocrit; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Microcirculation; Middle Aged; Recombinant Proteins; Renal Dialysis; Ultrasonography; Ventricular Dysfunction, Left

Secondary hyperparathyroidism is a frequent condition of dialysis patients. Endocrine derangements, with disturbance of calcium metabolism are complex, involving bone, heart (left ventricular hypertrophy-dilatation), bone marrow (anemia and erythropoietin resistance), muscle (increase of body fat mass) and insulin resistance. Aim of the study was to assess how these conditions are inter-correlated in the same patients. 45 patients (m 20, f 25; years 61.8 +/- 11.6) in maintenance bicarbonate three-weekly hemodialysis since > 3 years were studied. Cardiac function was assessed by echocardiography (EF%: left ventricular ejection fraction), which showed an inverse correlation both with parathormone (iPTH vs EF%: r = -0.64; p < 0.001) and with erythropoietin (rHu-EPO vs EF%: r = -0.62; p < 0.001). This suggests the possibility of a multi-endocrine resistance in dialysis patients with chronic renal failure, secondary to the degree of malnutrition. Lower lean mass is correlated with hyperparathyroidism (iPTH vs fat mass%: r = 0.37; p < 0.01), with lower left ventricular systolic function (EF% vs fat mass%: r = -0.41; p < 0.005) and with rHu-EPO resistance. Moreover, patients with higher iPTH show a hypercatabolic disposition, assessed as protein catabolic rate (PCR/kg vs iPTH r = 0.54; p < 0.001). This pattern can be a consequence of chronic renal failure, but bio-compatibility of materials can be involved as well.

Topics: Body Mass Index; Drug Resistance; Erythropoietin; Female; Hemoglobin A; Humans; Hyperparathyroidism, Secondary; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Contraction; Nutrition Disorders; Parathyroid Hormone; Recombinant Proteins; Renal Dialysis; Stroke Volume; Systole

Left ventricular hypertrophy (LVH) has been identified as an independent risk factor for mortality in patients with chronic renal failure (CRF) and anemia has been proposed to contribute to LVH. The cardiovascular and hemodynamic effects of correction of anemia with recombinant human erythropoietin (rHU EPO) was assessed in a 12 week prospective study in patients with CRF.. Biochemical parameters and echocardiography were studied at the start and after three months therapy with EPO in 24 patients with CRF--11 predialysis (Group I) and 13 dialysis (Group II).. The mean haemoglobin (Hb)--g/dl increased significantly from 7.5 +/- 1.0 to 10.1 +/- 1.1 in group I and from 6.7 +/- 0.6 to 9.4 +/- 0.8 in group II (p < 0.05) on EPO therapy. The left ventricular mass index (LVMi)--g/m2 reduced significantly from 185.6 +/- 44.6 to 158.3 +/- 4.1 in group I and from 158.0 +/- 26.9 to 131.6 +/- 22.1 in group II (p < 0.05 in both). The interventricular septal thickness (IVST) also showed a significant decline in both groups, 1.17 +/- 0.06 to 1.14 +/- 0.05 (group I) and 1.09 +/- 0.25 to 1.01 +/- 0.21 (group II), p < 0.05 in both. The thickness of the left ventricular posterior wall remained unchanged. The left ventricular end diastolic and systolic diameters (LVEDD and LVESD) significantly reduced from their baseline values in both the groups (p < 0.05). The diastolic filling parameters across the mitral valve remained unchanged in both the groups. The cardiac index (CI)--L/min/m2 decreased from 3.53 +/- 0.3 to 3.03 +/- 0.27 in group I and from 3.31 +/- 0.64 to 2.80 +/- 0.60 in group II (p < 0.05) and the total peripheral resistance (TPR)--dynes/cm5/sec increased from 1567 +/- 164.8 to 1883 +/- 190.7 in group I and from 1618 +/- 375.7 to 2004 +/- 437.3 in group II. The differences in all the parameters at the start and after 3 months of EPO were comparable in groups I and II. The mean arterial pressure (MAP) changed insignificantly in both the groups.. To conclude, this study has shown that the decrease in LVMi with EPO reflects the role of anemia in the genesis of LVH and that the correction of anemia with EPO in CRF results in regression of LVMi and has a favourable effect on cardiovascular hemodynamics.

Topics: Adolescent; Adult; Aged; Anemia; Echocardiography; Erythropoietin; Female; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Ventricular Function, Left

Angiotensin-converting enzyme (ACE) inhibitors have the capability of decreasing left ventricular mass index (LVMI) in chronic haemodialysis (HD) patients. On the other hand, recent reports provide conflicting information regarding the impact of ACE inhibitors on responsiveness to recombinant human erythropoietin (rHuEpo), and there are no data about the effect of withdrawing ACE inhibitors both on rHuEpo response and LVMI in HD patients.. ACE inhibitors were switched to another antihypertensive medication in 23 out of 68 patients in our HD unit who were receiving both rHuEpo and an ACE inhibitor for more than 1 year. Blood pressure at the pre- and post-dialysis phases, haematocrit levels and rHuEpo doses were determined at the end of the first and of the third years, and the LVMI was determined at the end of the third year. Statistical analyses were done in 15 patients in whom the study could be completed.. The mean (+/-SD) haematocrit level was increased from 26.3+6.4% to 29.8+/-6.3% at the first year (P<0.05), and to 29.4+/-6.5% at the third year (P<0.05 vs before), while the mean dose of rHuEpo was decreased from 208.3+/-99.0 UI/kg/week to 141.0+/-91.8 at the first year (P=0.01), and to 141.4+/-81.0 at the third year (P=0.01 vs before). Administration of rHuEpo had been stopped in two patients at the end of the first year. The mean blood pressure level and the mean LVMI were not changed (P>0.05 vs before). There were no significant changes in dialysis parameters, iron status, plasma renin activities, and levels of aldosterone, intact parathyroid hormone, aluminum and erythropoietin.. The findings of this small uncontrolled study indicate that withdrawal of ACE inhibitors in hypertensive chronic HD patients receiving rHuEpo may result in an increase in haematocrit level, and a decrease in dose of rHuEpo without any significant changes in the blood pressure level and LVMI. Controlled prospective studies are needed to clarify this issue.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Drug Therapy, Combination; Echocardiography; Erythropoietin; Female; Hematocrit; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Recombinant Proteins; Renal Dialysis

The aim of this study was to compare clinical and biological results in 4 standard hemodialyzed patients originally treated by three 4-5 h sessions per week and converted within one year to daily hemodialysis sessions of 2-2.5 h each 6 times per week. The modalities and the total weekly dialysis times remained the same. With daily hemodialysis, the blood pressure and left ventricular mass index decreased significantly (p < 0.01). A significant decrease in the urea time averaged deviation (TAD) (p < 0.005) and increase in the Kt/V index (p < 0.05) were observed. A gain in dry weight was shown with a rise in caloric intake from 33+/-3.21 to 40.8+/-6.35 kcal/kg/day (p < 0.05), and the normalized protein catabolic rate (nPCR) increased significantly (p < 0.0038). One patient who was receiving erythropoietin (EPO) for anemia could stop his treatment. No arteriovenous fistula complications were observed. Daily hemodialysis seems to be the method of choice to manage hypertension and left ventricular hypertrophy in uremic patients. The increase of the urea TAD to a value closer to that of the healthy kidney due to the increase of the frequency of dialysis is probably the main explanation for clinical improvement.

Topics: Adult; Aged; Anemia; Arteriovenous Shunt, Surgical; Blood Pressure; Energy Intake; Erythropoietin; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Proteins; Renal Dialysis; Time Factors; Ultrasonography; Urea; Uremia; Weight Gain

Topics: Cardiac Output; Erythropoietin; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Parathyroid Hormone; Renal Dialysis; Uremia

Topics: Adult; Aged; Anemia; Antihypertensive Agents; Blood Pressure; Erythropoietin; Female; Hematocrit; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Renal Dialysis; Retrospective Studies

The results of anemia correction by recombinant human erythropoietin (rHuEPO) therapy with regard to cardiac function and left ventricular hypertrophy in dialysis patients are controversially discussed. The aim of the study was to assess the effects of therapy rHuEPO on cardiac morphology and function in dialysis patients. We studied 11 clinically stable hemodialysis patients with severe renal anemia (hematocrit <27%) and increased left ventricular mass index (LVMi) with no history of coronary or valvular heart disease, systemic disease, severe hyperparathyroidism, hypertension stage 2 or higher, transfusion-dependent anemia, and concurrent rHuEPO treatment. The patients were treated with rHuEPO administered subcutaneously once or twice weekly at a mean dose of 80 +/- 31 IU/kg week until the hematocrit was >30% and underwent a complete Doppler echocardiographic study at baseline and at follow-up (after 12.2 +/- 2.9 months). At follow-up, ejection fraction and fractional shortening significantly increased from 62.7 +/- 13.8 to 67.8 +/- 9. 7% (p < 0.05) and from 35.5 +/- 9.8 to 39.4 +/- 7.1% (p < 0.05), respectively, whereas mean velocity of circumferential fiber shortening demonstrated a trend towards amelioration from 1.18 +/- 0. 23 to 1.27 +/- 0.27 circ/s (n.s.). LVMi and morphological data remained unchanged throughout the study. Nevertheless, LVMi changes showed two different behaviors with respect to baseline values: in 6 patients with higher baseline values, LVMi decreased from 229 +/- 36 to 191 +/- 45 g/m2 (p < 0.05), while it worsened in 5 patients with less marked LVMi, increasing from 141 +/- 32 to 186 +/- 40 g/m2 (p < 0.05). Our data demonstrate that partial correction of renal anemia with rHuEPO therapy seems to improve cardiac performance and to induce a regression of left ventricular hypertrophy, particularly in patients with greater baseline hypertrophy, ultimately confirming the multifactorial pathogenesis of left ventricular hypertrophy.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Body Weight; Echocardiography, Doppler; Erythropoietin; Female; Heart Function Tests; Hematocrit; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis; Ventricular Function, Left

Systemic hypertension may develop, or worsen, in 20-30% of haemodialysis patients treated with recombinant human erythropoietin (r-HuEPO). No particular group of patients, however, should be excluded from r-HuEPO treatment because of this increased risk. In the vast majority of cases, hypertension can be managed effectively by reducing dry weight, and by adding an antihypertensive agent if necessary. Only if these approaches are ineffective should the dose of r-HuEPO be reduced. Patients on dialysis are likely to be intolerant of cardiac ischaemia, as a result of coronary artery disease, microvascular occlusive disease, inadequate neo-vascularization in cardiac hypertrophy, or reduced glucose uptake (which impairs non-oxidative metabolism of the heart). Treatment with r-HuEPO can significantly reduce cardiac risk, as measured by surrogate endpoints such as left ventricular hypertrophy. More studies are urgently needed to investigate the potential beneficial effects of r-HuEPO on hard endpoints such as cardiac morbidity and mortality. In addition, dose-response data for target haematocrits in the range 30-40% are needed before an appropriate target haematocrit can be determined for patients with symptomatic vascular and cardiac disease.

Topics: Erythropoietin; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Myocardial Ischemia; Peripheral Vascular Diseases; Recombinant Proteins

The aim of our study was to evaluate cardiovascular function at rest and during exercise in dialysis patients before and after treatment with Epo and to examine the changes in left ventricular mass as the consequence of treatment for anaemia. We applied echocardiography and radionuclide ventriculography at rest and after exercise in our research. Following treatment with Epo there was a decrease in the initially high cardiac output (CO) and cardiac index (CI) from 7.5 to 6.31/min and from 4.3 to 3.61/min/m2 respectively. No changes were noted in mean diastolic (DPB) and mean blood pressure (MBP), as well as the initially increased peripheral resistance index (TPRi) of 2582.3 +/- 2097.3 dyn-s-cm-5.m2. Nevertheless, end-diastolic (EDV) and end-systolic (ESV) volume were significantly decreased (P < 0.05), but the ejection fraction (EF) remained unchanged (73.9%). The decrease in the mean values for left ventricular mass (LVM) was significant only within the subgroup of dialysed patients who initially had larger left ventricular mass (P < 0.01). The functional capacity of the CV system measured during exercise increased from four metabolic equivalents (METs) to 6 METs (P < 0.01). A significant increase in blood volume was also observed following treatment of anaemia. The haemodynamic consequences of Epo therapy for the treatment of anaemia were quite positive. However, we would like to point out certain concerns regarding the dialysed patients with initially lower values for left ventricular mass and cardiac output, since the patients within this group developed left ventricular hypertrophy and an increase in cardiac output.

Topics: Adult; Anemia; Chronic Disease; Echocardiography; Erythropoietin; Exercise Tolerance; Female; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Radionuclide Ventriculography; Renal Dialysis

The purpose of this study was to examine the effect of recombinant human erythropoietin (r-HuEPO) on left ventricular mass. Twenty-seven hemodialysis patients (13 men and 14 women) were given r-HuEPO for renal anemia. Blood pressure and heart rate were measured before and after the 16-week course of r-HuEPO, and at the same time echocardiography was performed to measure left ventricular dimensions and wall thickness. These measurements were used to calculate left ventricular volume, cardiac output (CO), and left ventricular mass (LVmass). Diastolic blood pressure (DBP) increased after administration of r-HuEPO (from 75.8 +/- 10.8 mmHg to 85.6 +/- 12.7 mmHg), but there was no change in systolic blood pressure (SBP) or heart rate. LVmass increased significantly in seven cases (from 194.7 +/- 40.0 g to 240.3 +/- 47.3 g). These cases, Group I, showed no decline in stroke volume (SV) or CO, and showed significant increases in SBP. In the remaining 20 cases, Group II, LVmass decreased or was unchanged. In this group SV and CO decreased, but there was no increase in SBP. We conclude that increases in LVmass may be associated with elevated systolic blood pressure and hypertrophy of the left ventricular wall, when hemodialysis patients with severe renal anemia are given r-HuEPO.

Topics: Adult; Aged; Anemia; Erythropoietin; Female; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Ventricular Function, Left

Children with end stage renal failure and anaemia have an increased cardiac index and often gross ventricular hypertrophy. Correction of anaemia with recombinant human erythropoietin (r-HuEpo) for less than six months results in a reduction in the cardiac index without a significant reduction in left ventricular hypertrophy. Seven children receiving dialysis (group 1) were studied to determine whether a reduction in left ventricular hypertrophy would occur after a 12 month period of r-HuEpo. A decrease in the cardiac index was seen by six months, and a significant reduction in left ventricular mass index and cardiothoracic ratio was seen by 12 months. Successful renal transplantation also results in a reduction in the cardiac index and left ventricular hypertrophy, but the relative contributions of correction of anaemia and correction of biochemical disturbance is unknown because they usually improve simultaneously. To investigate this, six children (group 2) who already had a mean haemoglobin concentration of 107 g/l while receiving dialysis were followed up for 12 months after successful transplantation. They showed no significant change in haemoglobin concentration, but a dramatic improvement in biochemistry. There was no significant change in cardiovascular function. Anaemia is the more dominant influence on cardiovascular function in end stage renal failure.

Topics: Adolescent; Anemia; Child; Child, Preschool; Erythropoietin; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Kidney Transplantation; Male; Recombinant Proteins; Renal Dialysis; Uremia

28 anemic [hematocrit (Hct) < 25%] and normotensive patients on maintenance hemodialysis with uremia-associated left-ventricular (LV) hypertrophy were treated with recombinant human erythropoietin. Before correction of anemia, after 4 months at a target Hct of 35% and 16 months (Hct still 35%) patients were assessed by echocardiography and physical stress testing. Partial correction of anemia resulted in a decrease in the LV end-diastolic diameter from 52.6 +/- 3.4 SD mm to 49.6 +/- 3.4 mm at 4 months (p < 0.01) and 47.9 +/- 2.9 mm at 16 months (p < 0.001). Concomitantly there was a slight decrease of LV end-systolic diameter (30.4 +/- 3.1 vs. 32.6 +/- 3.5 mm, p < 0.05) and LV posterior wall thickness (12.1 +/- 0.9 vs. 12.8 +/- 0.8 mm, p < 0.05) at 16 months. The calculated LV muscle mass index was reduced from 199 +/- 35 g/m2 to 173 +/- 34 g/m2 at 4 months (p < 0.01) and 160 +/- 28 g/m2 at 16 months (p < 0.001). Heart rate at rest was reduced significantly from 80 +/- 12 to 73 +/- 11 min (p < 0.01) at 4 and 16 months. LV ejection fraction, thickness of LV septum and blood pressure did not change. Partial correction of anemia led to an increase of maximal physical stress tolerance from 1.4 +/- 0.4 to 1.85 +/- 0.5 W/kg b.w. at 4 months (p < 0.01), which was maintained at 16 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Anemia; Blood Pressure; Erythropoietin; Female; Heart Rate; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Renal Dialysis; Time Factors; Uremia; Ventricular Function, Left

Topics: Anemia; Erythropoietin; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Ultrasonography

Topics: Adult; Anemia; Erythropoietin; Female; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Uremia