Effect Of Erythropoietin In Patients Research Articles

Treatment of Chronic Kidney Diseases with Darpeboetin can Ameliorate Kidney Functions: A Possible Clinical Relevance

Background: Erythropoietin (EPO) has been used clinically for the treatment of anemia as it was the first characterized hematopoietic factor. Erythropoietin is produced primarily by the kidneys (renal cortical fibroblasts) which induces proliferation and differentiation of erythroid progenitor cells. Previous studies suggested that erythropoietin may directly stimulates the regeneration of damaged tubular cells due to presence of erythropoietin receptors on renal tubular epithelial, mesangial and endothelial cells. EPO directly prevent glomerulosclerosis as a consequence of amelioration of podocyte injury. Therefore, to improve kidney function in chronic kidney disease (CKD), it is of critical importance to investigate clinically the beneficial reno-protective effects of EPO in patients with CKD. Methodology: The study was conducted at King Abdulaziz Medical City and included patients with chronic kidney diseases. Patients were under medical treatment with Darpeboetin for the first time. The administration frequency of Darpeboetin was single dose weekly. Kidney function tests including serum creatinine, serum urea, alkaline phosphatase, serum calcium, serum phosphorus, serum albumin and albuminuria were collected from the hospital electronic medical record system (BestCareR). Test values before and after treatment were compared. of the patients before starting treatment and at the end of treatment. The week before starting treatment was considered week 0 (baseline) Results: The results indicated that, treatment with a weekly single dose of Darpeboetin reduces blood urea nitrogen (BUN p=0.002) and serum uric acid level (p=0.009). The effect of treatment on serum calcium and potassium, showed a significant elevation of serum potassium (P<0.001), serum calcium (P<0.001) and adjusted calcium (P<0.001) levels parallel with significant decrease in serum phosphorus (p=0.004). Also treatment of chronic kidney disease patients significantly ameliorates serum albumin (P<0.001). Conclusion: Treatment with Darpeboetin may confirm the reno-protective potency. Darpeboetin is a promising drug to prevent or attenuate tissues kidney damage especially in chronic kidney disease

Effect of Erythropoietin in patients with acute myocardial infarction: five-year results of the REVIVAL-3 trial

BackgroundErythropoietin (EPO) has been suggested to promote cardiac repair after MI. However, the randomized, double-blind, placebo controlled REVIVAL-3 trial showed that short term high dose EPO in timely reperfused myocardium does not improve left ventricular ejection fraction after 6 months. Moreover, the study raised safety concerns due to a trend towards a higher incidence of adverse clinical events as well as a increase in neointima formation after treatment with EPO. The present study therefore aimed to assess the 5-year clinical outcomes.MethodsAfter successful reperfusion 138 patients with STEMI were randomly assigned to receive epoetin beta (3.33×104 U, n = 68) or placebo (n = 70) immediately, 24 and 48 h after percutaneous coronary intervention. The primary outcome of the present study- the combined incidence of MACE 5 years after randomization - occurred in 25% of the patients assigned to epoetin beta and 17% of the patients assigned to placebo (RR 1.5; 95% CI 0.8-3.5; p = 0.26). Target lesion revascularization was required in 15 patients (22.1%) treated with epoetin-ß and 9 patients (12.9%) treated with placebo (p = 0.15). Analysis of patients in the upper and lower quartile of baseline hemoglobin as an indirect estimate of endogenous erythropoietin levels revealed no significant impact of endogenous erythropoietin on efficiency of exogen administered epoetin-ß in terms of death and MACE.ConclusionThese long-term follow-up data show that epoetin beta does not improve clinical outcomes of patients with acute myocardial infarction.Trial registrationURL www.clinicaltrials.gov; Unique identifier NCT00390832; trial registration date October 19th 2006

Therapeutic effect of erythropoietin in patients with traumatic brain injury: a meta-analysis of randomized controlled trials.

OBJECTIVE Erythropoietin (EPO) exerts a neuroprotective effect in animal models of traumatic brain injury (TBI). However, its effectiveness in human patients with TBI is unclear. In this study, the authors conducted the first meta-analysis to assess the effectiveness and safety of EPO in patients with TBI. METHODS In December 2015, a systematic search was performed of PubMed, Web of Science, MEDLINE, Embase, the Cochrane Library databases, and Google Scholar. Only English-language publications of randomized controlled trials (RCTs) using EPO in patients with TBI were selected for analysis. The assessed outcomes included mortality, favorable neurological outcome, hospital stay, and associated adverse effects. Continuous variables were presented as mean difference (MD) with a 95% confidence interval (CI). Dichotomous variables were presented as risk ratio (RR) or risk difference (RD) with a 95% CI. Statistical heterogeneity was examined using both I2 and chi-square tests. RESULTS Of the 346 studies identified in the search, 5 RCTs involving 915 patients met the inclusion criteria. The overall results demonstrated that EPO significantly reduced mortality (RR 0.69, 95% CI 0.49-0.96, p = 0.03) and shortened the hospitalization time (MD -7.59, 95% CI -9.71 to -5.46, p < 0.0001) for patients with TBI. Pooled results of favorable outcome (RR 1.00, 95% CI 0.88-1.15, p = 0.97) and deep vein thrombosis (DVT; RD 0.00, 95% CI -0.05 to 0.05, p = 1.00) did not show a significant difference. CONCLUSIONS The authors suggested that EPO is beneficial for patients with TBI in terms of reducing mortality and shortening hospitalization time without increasing the risk of DVT. However, its effect on improving favorable neurological outcomes did not reach statistical significance. Therefore, more well-designed RCTs are necessary to ascertain the optimum dosage and time window of EPO treatment for patients with TBI.

Neuroprotective Effects of Erythropoietin in Patients with Severe Closed Brain Injury.

Our research was focused on the neuroprotective function of erythropoietin (Epo) in patients with severe closed traumatic brain injury (TBI). Our model examined the influence of the outcome and neurological recovery in 42 adults with TBI who were admitted to ICU within 6 hours of their injury and were recruited into a randomized controlled study of two groups; only the patients of the intervention group received 10,000 i.u. of Epo for 7 consecutive days. A prognostic model based on CRASH II injury model and outcome was measured by survival and Glasgow Outcome Scale-Extended version (GOS-E) score at 6 months post-injury. Six patients (18.7%) died during the first two weeks; 4 of the control group and 2 of the intervention group. A mortality rate of 22.2% and 8.3% for the control and intervention group respectively was observed. A lower rate of good outcome (GOS-E score > 4) at 6 months was mentioned among patients of the control group. The study provides evidence of lower mortality and better neurological outcome for the patients who received Epo increasing the possibility that Epo therapy could be used in clinical practice, limiting neuronal damage induced by TBI.

Effect of erythropoietin in patients with acute myocardial infarction: two-year results of the REVIVAL-3 trial

Effect of erythropoietin in patients with acute myocardial infarction: two-year results of the REVIVAL-3 trial

Neuroprotective Effects of Erythropoietin in Patients with Carbon Monoxide Poisoning

The purpose of this study was to evaluate the efficacy of erythropoietin (EPO) for treating patients with carbon monoxide (CO) poisoning. We conducted a randomized, prospective study of 103 patients with CO poisoning in two groups: an EPO group (n = 54; patients received EPO) and a placebo group (n = 49; patients received normal saline). The study endpoints were the functional outcome at day 30 (the Barthel index and neurologic sequelae), National Institutes of Health Stroke Scale (NIHSS) score, and the levels of S-100β. At 18 days, the NIHSS score improved significantly and S-100β levels significantly decreased in patients in the EPO group. At 30 days, patients in the EPO group had a superior Barthel index and fewer patients had delayed neurologic sequelae (DNS). This study demonstrated that early administration of EPO to patients with CO poisoning improved neurological outcomes and reduced the incidence of DNS.

Erythropoietin treatment in patients with acute myocardial infarction: A meta-analysis of randomized controlled trials

In experimental models of acute myocardial infarction (AMI), erythropoietin (EPO) reduces infarct size and improves left ventricular (LV) function. However, in the clinical setting, the effect of EPO in AMI was unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of EPO to explore the safety and therapeutic effects of EPO in patients with AMI. We identified reports of RCTs comparing EPO to placebo for AMI in adult humans in PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Outcomes included all-cause mortality, major cardiovascular events, cardiac function by LV ejection fraction and infarct size. We included 13 articles of RCTs with data for 1,564 patients. Erythropoietin therapy did not improve LV ejection fraction (weighted mean difference [WMD] 0.33, 95% CI -1.90 to 1.24, P = .68) and had no effect on infarct size, as measured by cardiac magnetic resonance imaging (WMD -0.12, -2.16 to 1.91, P = .90) or serum peak value of creatine kinase-MB (WMD -2.01, -25.70 to 21.68, P = .87). Erythropoietin treatment did not decrease the risk of total adverse cardiac events (relative risk [RR] 1.02, 0.65-1.61, P = .92). Erythropoietin treatment also failed to decrease the risk of heart failure (RR, 0.69, 0.27-1.72, P = .42) and all-cause mortality (RR 0.55, 0.22-1.33, P = .18). Moreover, EPO had no effect on the risk of stent thrombosis (RR, 0.69, 0.29-1.64, P = .40). Erythropoietin in patients with AMI seems to have no clinical benefit for heart function or reducing infarct size, cardiovascular events, and all-cause mortality. Erythropoietin may not be a choice for patients with AMI.

Renovascular Protective Effects of Erythropoietin in Patients with Chronic Kidney Disease

Erythropoietin (EPO) has been widely used for the treatment of anemia in chronic kidney disease (CKD). A growing body of evidence indicates that the therapeutic benefits of EPO could extend beyond the improvement of anemia. The aim of the present study was to determine whether EPO affects renovascular and oxidative stress biomarkers in pre-dialysis CKD patients with anemia. The study was a single-arm prospective study. Fifteen CKD patients (9 males and 6 females, mean age 63 years) with anemia (mean Hb: 8.1 g/dL) were treated with recombinant human EPO; 12,000 U administered subcutaneously once every 2 weeks. Various parameters were measured before and 6 months after treatment. These included serum hemoglobin (Hb), creatinine, estimated glomerular filtration rate (eGFR), proteinuria, urinary liver-type fatty acid binding protein (L-FABP--a biomarker of renal injury), urinary 8-hydroxydeoxyguanosine (8-OHdG--a marker of oxidative stress), serum asymmetrical dimethylarginine (ADMA), carotid artery intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) as vascular markers and plasma brain natriuretic peptide (BNP) levels and left ventricular ejection fraction (LVEF) as cardiac function markers and cardio-thoracic ratio (CTR) and inferior vena cava dimension (IVCS) as extra fluid retention markers. After 6 months, serum Hb was significantly increased (p<0.001) and urinary levels of protein, L-FABP and 8-OHdG, carotid IMT, baPWV, plasma BNP and serum ADMA levels were significantly decreased (p<0.001). Serum creatinine, eGFR, LVEF, CTR and IVCS showed little difference throughout the experimental period. These data suggest that recombinant human EPO may ameliorate renal injury, oxidative stress and progression of atherosclerosis in addition to improving anemia in CKD patients.

Erythropoietin in patients with aneurysmal subarachnoid haemorrhage: a double blind randomised clinical trial

Erythropoietin (EPO) is neuroprotective in experimental models of stroke and subarachnoid haemorrhage (SAH) and possibly in patients with thromboembolic stroke. We studied the efficacy and safety of EPO in patients with SAH. A larger scale clinical trial was planned but preliminarily terminated because of a lower than expected inclusion rate. However, 73 patients were randomised to treatment with EPO (500 IU/kg/day for three days) or placebo. The primary endpoint was Glasgow Outcome Score at six months. We further studied surrogate measures of secondary ischaemia, i.e. transcranial Doppler (TCD) flow velocity, symptomatic vasospasm, cerebral metabolism (microdialysis) and jugular venous oximetry, biochemical markers of brain damage (S-100beta and neuron specific enolase) and blood-brain barrier integrity. The limited sample size precluded our primary hypotheses being verified and refuted. However, data from this study are important for any other study of SAH and as much raw data as possible are presented and can be included in future meta analyses. On admission the proportion of patients in a poor condition was higher in the EPO group compared with the placebo group but the difference was statistically insignificant. In the EPO-treated patients the CSF concentration of EPO increased 600-fold. Except for a higher extracelullar concentration of glycerol in the EPO group probably caused by the poorer clinical condition of these patients, there were no statistically significant group differences in the primary or secondary outcome measures. EPO was well tolerated. Beneficial effects of EPO in patients with SAH cannot be excluded or concluded on the basis of this study and larger scale trials are warranted.

Effects of Subcutaneous Recombinant Human Erythropoietin in Patients on Continuous Ambulatory Peritoneal Dialysis

The use of recombinant human erythropoietin (rHuEPO) has revolutionized the treatment of renal anemia, but the dose regimens, the optimal frequency, and the effects on other target organs like the central nervous systems (CNS) are still under discussion. We designed a prospective, ongoing study with 10 stable continuous ambulatory peritoneal dialysis (CAPD) patients (6 males, 4 females; mean age 64.4 +/- 7.8 years), with a pretreatment hemoglobin (Hb) < 7.0 g% and requiring regular blood transfusions. Seven patients were treated with 4000 U rHuEPO once weekly (Eritrogen, Boehringer Mannheim), 2 patients received 4000 U every 5 and 8 days, and the last one 4000 U every 10 days. The target hematocrit was 33% and Hb 10.0 g%. The CNS activity was recorded as visual (VEP), brainstem (BAER), and somatosensory (SEP)-evoked potentials. The mean Hb concentration increased from 6.9 +/- 1.2 g% to 10.3 +/- 1.6 g% (p < 0.001) over 8 weeks. There were no significant changes in urea, creatinine, and potassium levels, and urine output. rHuEPO induced a decrease in latency of P100 VEP, in the four main components of BAER, and in the P27-N35 intertime of SEP. Parallel to the improvement of red cell indices, patients experienced a dramatic improvement in well-being. The subcutaneous administration of a single vial of rHuEPO is safe, convenient, and inexpensive in CAPD. The role of rHuEPO treatment in improving the electrophysiological brain function in uremic and anemic patients remains to be studied and may not necessarily be based on improved cerebral oxygenation.

Hemodynamic and Cardiac Effects of Erythropoietin in Patients on Regular Dialysis

The long-term impact of erythropoietin (EPO) treatment on cardiac structures and function was prospectively studied in eight hypertensive (Group I) and seven normotensive (Group II) patients on hemodialysis (HD). Doppler-echocardiograms were done before EPO and at two and twelve months of treatment. Mean hemoglobin (+/- SD) before EPO was 6.4 +/- 0.9; it rose significantly up to two months and then remained constant. At two months, cardiac index (CI) had significantly decreased, while peripheral vascular resistances increased. Five patients required increased antihypertensive drug treatment. No changes were seen in myocardial parameters at this short follow-up. After one year, left ventricular mass index (LVMi) decreased (p less than 0.05) in both groups concomitantly with a decrease in diastolic diameter and septum and posterior wall thicknesses. Basal LVMi was higher in Group I than in Group II, and after one year the regression was more marked in Group II. Left cardiac work showed prompt and steady improvement in both groups. Maintained partial correction of anemia with EPO during one year was associated with a return to normal of high CI, decreased left cardiac work and impressive regression of left ventricular hypertrophy.

Effect of erythropoietin in patients with myeloma.

Effect of erythropoietin in patients with myeloma.