应用红细胞生成素改善血液透析患者的营养状况

目的　了解红细胞生成素（EPO）对血液透析患者营养状况的影响。方法对25例血透患者在应用红细胞生成素前，治疗后3月、6月分别进行营养状况的评价，包括膳食摄入分析、人体学、生化指标和血浆氨基酸谱的测定。结果红细胞生成素治疗后的蛋白质、能量摄入以及各营养指标均较治疗前增加，其中以治疗6月后的蛋白质、能量摄入和三头肌皮褶厚度（TSF）、转铁蛋白（TF）、纤维连接蛋白（FN）的增加更为显著。血浆氨基酸中，亮氨酸、缬氨酸和丝氨酸在治疗后有增加，精氨酸、鸟氨酸和甘氨酸则有下降，尤以6月后的变化更为显著。结论红细胞生成素在纠正血透患者贫血的同时可改善其营养状况。     

Body mass index and resistance to recombinant human erythropoietin therapy in maintenance hemodialysis patients

Abstract

The aim of this work was to contribute to a better understanding of the relationship between resistance to recombinant human erythropoietin (rhEPO) therapy and body mass index (BMI) in hemodialysis (HD) patients. We evaluated 191 HD patients and 25 healthy individuals. Complete blood count, reticulocyte count, and circulating levels of ferritin, transferrin, iron, soluble transferrin receptor (sTfR), transferrin saturation, hepcidin, C-reactive protein (CRP), interleukin 6 (IL-6), albumin, and adiponectin were measured in all patients and controls. Non-responder patients (n?=?16), as compared with responder patients (n?=?175), showed statistically significant lower BMI values, an enhanced inflammatory and higher adiponectin levels, associated with disturbances in iron metabolism. Analyzing the results according to BMI, we found that underweight patients required higher rhEPO doses than normal, overweight, and obese patients, and a higher percentage of non-responders patients were found within the underweight group of HD patients. Moreover, underweight patients presented lower levels of transferrin and higher levels of adiponectin compared to overweight and obese patients, and lower levels of iron compared with normal weight patients. Multiple regression analysis identified the sTfR, hemoglobin, BMI, and albumin as independent variables associated with rhEPO doses. In conclusion, our work showed that HD patients resistant to rhEPO therapy present a functional iron deficiency and a higher degree of inflammation, despite their lower BMI values and higher levels of adiponectin. Actually, BMI is poorly related with markers of systemic inflammation, such as IL-6 and CRP, while adiponectin works a fairly good indirect marker of adiposity within HD patients.     

Red blood cell lifespan in long-term hemodialysis patients treated with roxadustat or recombinant human erythropoietin

IntroductionA significant decrease in red blood cell (RBC) survival has been observed in patients with renal failure, which is supposed to contribute to renal anemia. The aim of this observational study was to determine RBC survival in hemodialysis (HD) patients treated with roxadustat or recombinant human erythropoietin (rhuEPO) compared with healthy persons.MethodsRBC lifespan was measured by Levitt’s CO breath test with newly developed automatic instrument ELS Tester.ResultsA total of 102 patients receiving long-term HD from two independent dialysis centers enrolled in the study, of whom 62 were treated with rhuEPO and 40 were on roxadustat therapy. A total of 25 healthy participants were recruited to match HD participants according to age and sex. Median RBC survival times in rhuEPO, roxadustat, and control groups were 65.0 (25th–75th percentile, 49.5–77.3), 75.5 (25th–75th percentile, 57.3–99.3), and 108.0 (25th–75th percentile, 89.0–141.5) d, respectively. Patients treated with roxadustat had significantly longer RBC survival time than patients treated with rhuEPO (p < .05). In multivariate analysis of factors affecting RBC lifespan in the whole HD patients, anemia treatment drugs (rhuEPO/roxadustat) and levels of hemoglobin were the significantly independent factors. RBC survival was not found to correlate with either weekly rhuEPO dosage (r = –0.087, p = .500) or weekly roxadustat dosage (r = −0.267, p = .110) in our cohort.ConclusionsHD patients treated with roxadustat had significantly longer RBC survival time than patients treated with rhuEPO, large prospective studies with long-term follow-up are warranted to verify the results in future. Abbreviations RBC: red blood cell; HD: hemodialysis; rhu EPO: recombinant human erythropoietin; ESRD: end-stage renal disease; EPO: erythropoietin; ROS: reactive oxygen species; CKD: chronic kideny disease; ESAs: erythropoiesis-stimulating agents; HIF-PHD: hypoxia-inducible factor prolyl hydroxylase; CO: carbon monoxide; Hb: hemoglobin     

Hemoglobin cycling in hemodialysis patients treated with recombinant human erythropoietin

BACKGROUND: Treatment with recombinant human erythropoietin (rHuEPO) has been a major advance for the management of anemia in patients on hemodialysis. Therapy, however, is often observed to be associated with recurrent cyclic fluctuations in hemoglobin levels. The purpose of this analysis was to describe the phenomenology of hemoglobin cycling during rHuEPO treatment. METHODS: Data were analyzed for 281 hemodialysis patients treated at Winthrop-University Hospital Dialysis Centers between 1998 and 2003. Eligible patients' first full 1-year period with less than 10 hospital days was studied. Hemoglobin cycling (cycles with amplitude >1.5 g/dL and duration >8 weeks) and excursions (half of one full cycle) were analyzed. RESULTS: Greater than 90% of patients experienced hemoglobin cycling. The mean number of hemoglobin excursions was 3.1 +/- 1.1 per patient/year. The mean amplitude per hemoglobin excursion was 2.51 +/- 0.89 g/dL. The mean duration of hemoglobin excursions was 10.3 +/- 5.1 weeks. Factors associated with initiation of up excursions included increases in rHuEPO dose (84%), intravenous iron treatment initiation or increase in dose (27%), posthospital discharge (36%), factors associated with down excursions included rHuEPO dose hold (15%) or dose reduction (62%), infection (6%), discontinuation of intravenous iron therapy (5%), and hospitalization (14%). Patients with frequent hemoglobin cycling (>two full cycles per year) were characterized as being more responsive to rHuEPO [index of EPO responsiveness (ERI) 1036 +/- 659 compared to 1992 +/- 701 for other patients] (P = 0.02). CONCLUSION: Hemoglobin cycling is a common occurrence in rHuEPO-treated hemodialysis patients. It is most closely associated with frequent rHuEPO dose changes, hospitalization, and iron treatment practices.     

Exercise in hemodialysis patients after treatment with recombinant human erythropoietin

To assess the effect of substantial increases in blood hemoglobin (Hb) caused by treatment with recombinant human erythropoietin (rhEPO) on exercise capacity in maintenance hemodialysis patients, we evaluated 10 patients (7 men and 3 women) at a mean age of 44.3 +/- 8.4 years on maintenance hemodialysis for a mean of 29.7 +/- 30.2 months by treadmill exercise to exhaustion. The patients were tested before administration of rhEPO and after a minimum 1 g/dl rise in Hb. With a change in Hb from 7.1 +/- 1.4 to 9.8 +/- 2.1 g/dl, peak oxygen consumption (VO2 peak) with exercise increased 50.3 +/- 9% (T1 = 15.1 +/- 5.3, T2 = 22.7 +/- 4.6 ml O2/kg/min, p less than 0.05). Respiratory exchange ratio (RER) at a given submaximal exercise level (3 mph, 6% of elevation) decreased significantly (T1 = 1.13 +/- 0.24, T2 = 0.92 +/- 0.08, p less than 0.05). The rhEPO-mediated increase in Hb was associated with an increased VO2 peak--an improvement of the peak exercise capacity and a reduced submaximal RER--reflecting a reduction in anaerobic metabolism at activities of daily living.     

Haemodialysis efficiency after long-term treatment with recombinant human erythropoietin

In 11 chronic haemodialysis patients we investigated whether the increase in haematocrit during recombinant human erythropoietin (rHuEPO) treatment might alter the long-term efficiency of haemodialysis. After correction of anaemia with rHuEPO (mean Ht 35 +/- 2% vs 19 +/- 2% at baseline) (p 0.001), mean predialysis creatinine and urea did not change, while predialysis phosphate (1.77 +/- 0.38 vs 1.51 +/- 0.29 mmol/l) were significantly increased (p 0.01). In six of the 11 rHuEPO treated patients a post- versus pre-dialysis haemoconcentration (haematocrit 44% vs 35%) not attributable to different ultrafiltration regimes, was observed. In these 6 patients mean predialysis phosphate, creatinine and urea tended to be higher, but not significantly, in comparison to he remaining 5 patients who did not haemoconcentrate. Dialyser clearances and total extractions for urea, creatinine, phosphate and inulin were compared to those of 11 matched haemodialysis patients with anaemia. No differences were observed either for small and middle molecule clearances or their extractions between rHuEPO and anaemic patients. In conclusion, dialysis efficiency is not affected if haematocrit values are kept about 35%.     

罗沙司他胶囊对比重组人促红素注射液治疗维持性血液透析肾性贫血的有效性及安全性

目的 比较罗沙司他胶囊和重组人促红素注射液（rhEPO）治疗维持性血液透析患者肾性贫血的有效性和安全性。方法 选取2020年9月至2020年11月在本院进行维持性血液透析治疗的40例肾性贫血患者,采用随机抽签法将其分为试验组和对照组,每组各20例。试验组使用罗沙司他胶囊治疗,对照组使用rhEPO治疗,研究进行12周。比较两组患者的红细胞计数（RBC）、血红蛋白（Hb）、红细胞比容（Hct）、铁蛋白（SF）、转铁蛋白（TRF）、转铁蛋白饱和度（TS）、三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）及不良反应。结果 治疗前,两组的RBC、Hb、Hct、SF、TRF、TS、TG、TC、LDL比较,差异均无统计学意义 (均P>0.05),治疗12周后,试验组的RBC、Hb、Hct、SF、TRF、TS均高于对照组,而试验组的TG、TC、LDL均低于对照组,差异均有统计学意义（均P<0.05）。两组均无严重不良反应出现。结论 罗沙司他胶囊可以明显改善维持性血液透析患者的肾性贫血,还可降低血脂水平,改善患者铁的利用率,其药效起效快,耐受性好,安全性较高,对肾性贫血患者是一种很好的选择。     

Nutritional assessment in anemic hemodialysis patients treated with recombinant human erythropoietin

Nutritional status was assessed in 25 anemic hemodialysis patients before and during erythropoietin treatment. Nutritional assessment included regular blood chemistry determinations, anthropometric measurements, analysis of protein content in skeletal muscle, and estimation of daily protein intake from protein catabolic rate determinations (using urea kinetic modelling) and dialysis efficiency for urea. These measurements were done immediately prior to erythropoietin treatment, after anemia correction and after one year of maintenance erythropoietin treatment. Both relative body weights and subcutaneous fat stores were low at the start, but increased significantly (p less than 0.05) during the study. Sixteen of the 25 patients gained weight and eight patients lost weight. The patients with weight gain had at the start of the study low weight indices (body weight 89.9 +/- 7.6% of ideal body weight, body mass index 20.6 +/- 1.6), significantly (p less than 0.005) lower than the patients with weight loss. Although protein malnutrition was not obvious from arm anthropometrics, alkali soluble protein/DNA ratio or from serum albumin determinations, ASP/DNA ratio, increased in three of five patients investigated after one year on erythropoietin treatment. Neither protein catabolic rate nor dialysis efficiency changed significantly during the study. We conclude that anemia correction with erythropoietin has a positive effect on malnutrition in hemodialysis patients. In patients with underweight, an adjustment of fat stores was initially observed, followed possibly by an improvement in muscle protein content.     

Low-dose recombinant human erythropoietin therapy in chronic hemodialysis patients

To test the hypothesis that low-dose recombinant human erythropoietin (r-HuEpo) would be effective and safe therapy for the anemia of end-stage renal failure, we studied 37 chronic hemodialysis patients for 3 months before and 6 months after beginning treatment with r-HuEpo, 3,000 U, administered initially intravenously (IV) three times weekly. Hematocrit increased from a mean of 25.2 vol% into the target range (mean, 32.2 vol%, a 28% increase) by 4 months. Transfusion requirements were dramatically reduced. Eight patients (22%) had exacerbated or new development of hypertension, while in trials using higher doses this occurred in 35%. Vascular access thrombosis, dialyzer clotting, and seizures were not seen more frequently during r-HuEpo therapy. Dialyzer reuse was not affected. Low-dose r-HuEpo therapy is effective in most hemodialysis patients and may be associated with less adverse effects because of the slower increase in blood viscosity. As targets are reached, downward dosage adjustments need to be smaller when using an initial low-dose regimen.     

Fibrinolytic capacity in hemodialysis patients treated with recombinant human erythropoietin.

A major adverse effect of recombinant human erythropoietin (r-HuEPO) in hemodialyzed patients are thrombotic events. Several reports on platelet function during r-HuEPO treatment have been published but less is known about fibrinolysis. In the present study, the fibrinolytic capacity was studied in 20 patients on maintenance hemodialysis and treated with r-HuEPO. The patients were randomized into two groups and investigated in a crossover design. r-HuEPO was administered intravenously and subcutaneously in each group and was given for 3 months, respectively. Plasma tissue plasminogen activator (t-PA) and released t-PA remained unaffected by r-HuEPO in both groups throughout the study. Tissue plasminogen activator inhibitor (PAI) increased in a cyclic way reaching peak values 4-6 weeks after the start of investigation and again 4-6 weeks after changing therapy. The increase in PAI was significant in the two groups (0.025 > p > 0.01). Tissue plasminogen antigen was low in the uremic patients. The influence of r-HuEPO on this parameter was not investigated. Compensatory changes in plasma levels of factor XII procoagulant activity, activated protein C and of alpha 2-antiplasmin were not observed. Thrombotic events occurred in 4 patients at peak values of PAI. Six patients required an increase in heparin dose simultaneously with the increase in PAI. Thus, r-HuEPO seemed to affect the fibrinolytic capacity of uremic patients.     

围手术期应用重组人促红细胞生成素21例的经验

目的　观察围手术期患者使用重组人促红细胞生成素 (rHuEPO)在纠正贫血和减少异体输血的临床效果。方法　 2 1例腹部择期手术患者 (术前贫血或预计出血量约 4 0 0～ 6 0 0ml或预计需输血 2～ 3U)分成治疗组和对照组 ,治疗组术前每周给予rHuEPO 30 0IU/kg ,分 3次皮下注射 ,同时口服速力菲 30 0mg/d ,共 2周。对照组术前 2周口服速力菲 30 0mg/d。观察术前贫血纠正、术中减少异体输血、术后恢复的效果。结果　治疗组用药后RBC、Hgb、Hct较术前基础值分别升高 0 36×10 12 /L、13 3g/L和 3 8% ,术中异体输血量少于对照组 (P <0 0 5 ) ,术后恢复改善 ;对照组无明显变化 ,甚至下降。结论　中等量失血的围手术期患者使用rHuEPO在纠正贫血和减少异体输血是有效的方法     

促红细胞生成素治疗急性脊髓损伤

目的 观察促红细胞生成素(EPO)对急性脊髓损伤神经功能恢复的疗效.方法 急性脊髓损伤患者65例,根据用药分为EPO治疗组35例和对照组30例;分别于入院时及治疗后末次随访时对脊髓损伤程度按ASIA2000评分标准进行神经功能评定,观察两组差异;同时监测患者用药前后血常规及血清EPO浓度,记录不良反应.结果 65例患者术后随访1～3年,平均1.7年,末次随访时治疗组患者ASIA运动、触觉、痛觉功能评分为58,2±8.2、78.5±11.5、82.6±13.5,显著优于对照组运动、触觉、痛觉功能评分45.6±6.8、65.5±13.4、68.7±14.7,差异有统计学意义(P<0.05),EPO组治疗过程中未见明显不良反应.结论 促红细胞生成素是治疗急性脊髓损伤安全有效的药物,早期应用EPO对促进患者神经功能的改善与恢复具有积极意义.     

Echocardiographic findings in patients on maintenance hemodialysis substituted with recombinant human erythropoietin

Cardiomegaly and impaired myocardial function are frequent in patients on maintenance hemodialysis. One important reason is probably severe renal anemia. Substitution with recombinant human erythropoietin (rhEPO) results in long-term correction of renal anemia. We investigated the changes in cardiac function under rhEPO therapy using echocardiography. 13 patients with severe renal anemia (hct less than 26%) but independent of regular blood transfusions during the last six months were treated with 40-120 IU/kg rhEPO intravenously three times/week. Echocardiographic studies were performed in the anemic state and when hematocrit values were stable at levels above 30%. Left ventricular end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD) were reduced (LVEDD: 53.9 +/- 4.2 mm vs. 51.4 +/- 5.8 mm; LVESD: 35.7 +/- 5 mm vs. 32.8 +/- 5 mm). Mean end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were also diminished (LVEDV: 141.9 +/- 25.4 ml vs. 128.1 +/- 32.5 ml; LVESV: 54.8 +/- 18.6 ml vs. 45.1 +/- 17 ml). Stroke volume (SV) fell slightly from 87.1 ml to 83 ml resulting in a decrease of cardiac output (CO) from 6.9 +/- 1.6 l/min to 6.2 +/- 1.7 l/min. The thickness of the left ventricular posterior wall (LVPW) and of the septum interventriculare (IVS) remained constant. Myocardial contractility indicated by ejection fraction (EF), fractional shortening (FS) and the velocity of circumferential fiber shortening (VCF) frequently improved. Our data indicate that correction of renal anemia by rhEPO can improve myocardial function in patients on maintenance hemodialysis.     

Skeletal effects of erythropoietin in hemodialysis patients

AIMS: To assess the effects of erythropoietin (EPO) on bone metabolism in patients receiving chronic hemodialysis (HD). METHODS: Forty one patients were divided into two groups whether they required the administration of EPO to treat renal anemia or not. Serial measurements of predialysis blood samples and bone mineral density were performed prospectively over a year. RESULTS: The administration of EPO was associated with an increased serum creatinine (11.9 +/- 0.4 to 12.5 +/- 0.4 mg/dl, p < 0.05), insulin-like growth factor binding protein (3.0 +/- 0.2 to 3.4 +/- 0.2 micrograms/ml, p < 0.05) as well as decreased iron level (112 +/- 7 to 88 +/- 7 micrograms/dl, p < 0.005). Furthermore, in EPO-treated group, exogenous EPO doses correlated with the increments in 1,25-dihydroxy-vitamin D (r = 0.38, p < 0.05), intact osteocalcin (r = 0.42, p < 0.05) and bone alkali-phosphatase (r = 0.53, p < 0.005), but not intact parathyroid hormone (r = 0.09). Both metacarpal index (0.47 +/- 0.02 to 0.47 +/- 0.02) and the summation of gray scale/diameter (2.68 +/- 0.06 to 2.61 +/- 0.07 mmAl), bone mineral density parameters, remained unchanged. CONCLUSION: The present data provide evidence that EPO may modulate the production of 1,25-dihydroxy-vitamin D in HD patients. Furthermore, our findings suggest that EPO therapy activates insulin-like growth factor system in HD patients, possibly through its actions on metabolism.     

Intradialytic hypotension is associated with dialytic age in patients on chronic hemodialysis

Abstract

Objective: Intradialytic hypotension (IDH) is common in patients on chronic hemodialysis, but knowledge on determinants is still unclear. The present study aims at evaluating the association between IDH and dialytic age (DA) in patients on chronic hemodialysis. Methods: Between January 2012 and January 2013, 82 patients on chronic hemodialysis for at least 1?year were screened for inclusion in the present study. Of these, 14 were excluded because of advanced heart failure (n.9), history of alcohol/substance abuse (n.1), diagnosis of dementia (n.2), actual instability of clinical conditions requiring hospitalization (n.2). IDH was defined as a decrease in systolic blood pressure ≥20?mmHg or a decrease in mean arterial pressure (MAP) by 10?mmHg associated with clinical events and need for nursing interventions. The number of IDH episodes in 10 consecutive hemodialysis sessions was recorded for each patient. Linear and logistic regressions were adopted to assess the adjusted association between IDH and DA. Results: The mean DA was 92?±?81. Eleven patients (16%) experienced IDH. DA was associated with IDH (OR?=?1.01; 95% CI?=?1.01–1.02; p?=?0.048), after adjusting for potential confounders. DA was associated with the numbers of IDH events in the unadjusted model (B?=?0.02; 95% CI?=?0.01–0.03; p?=?0.042), after adjusting for age and sex (B?=?0.01; 95% CI?=?0.01–0.03; p?=?0.042) as well as in the multivariable model (B?=?0.02; 95% CI?=?0.01–0.05; p?=?0.045). Conclusion: DA is associated with an increased probability of IDH and with increased number of IHD events. Studies are needed to understand the underlying factors of such an association.     

超纯透析液对血液透析患者促红素低反应性的影响

目的 探讨超纯透析液对维持性血液透析患者促红细胞生成素低反应性的影响.方法 选择维持性血液透析患者70例,随机分为普通透析液组(CD组,35例)和超纯透析液组(UPD组,35例),随访1年后观察两组超敏C反应蛋白(hs-CRP)和促红细胞生成素抵抗指数(Erythropoietin resistance index,ERI)的差异.结果 ①以ERI为因变量进行多元逐步线性回归分析,显示hs-CRP是ERI最为重要的独立影响因素(R2=0.699,p＜0.001);②随访1年后两组间hs-CRP差异有统计学意义(5.12±2.74 vs 3.77±2.19,P＜0.05),超纯透析液组ERI有明显改善(11.06±5.27 vs 16.42±7.05,p＜0.01).结论 ①C-反应蛋白升高是促红细胞生成素抵抗的独立影响因素;②使用超纯透析液可改善患者炎症状态和促红素低反应性.     

Antibodies in alloimmunized uraemic patients treated with recombinant erythropoietin

Abstract We have retrospectively analysed sera from 52 already sensitized uraemic patients collected over 1 year and compared erythropoietin (EPO)-treated with non-EPO-treated patients. Significantly fewer (P<0.01) patients (33%) on dialysis because of the rejection of their kidney grafts received EPO than patients on dialysis because of underlying kidney disease (71%). EPO treatment reduced the number of additional blood transfusions, since 3/28 EPO-treated but 12/24 non-EPO-treated patients were given blood (P<0.05). Among the EPO-treated patients, 64% showed a loss of panel-reactive antibodies (PRA), as measured by the microlymphocytotoxic technique, while only 12.5% of the non-treated patients showed a loss of PRA (P<0.01). In the subgroup of transplanted patients, PRA loss was only found among the EPO-treated patients, but their number was. small (P<0.05). The class, subclass and specificities of the antibodies, as determined by FACS (flow cytometry) analyses, showed no distinct differences between EPO- and non-EPO-treated patients. The differences were significant between transfused and previously transplanted patients.     

Vascular changes in hemodialysis patients in response to recombinant human erythropoietin

The partial correction of anemia with recombinant human erythropoietin (rHuEpo) is frequently associated with an increase in arterial pressure and could oppose the beneficial effect of anemia correction on myocardial function. In order to analyze the influence of rHuEpo therapy on the vessels and the heart, we performed systemic and regional hemodynamics studies in 11 hemodialysis patients before and 10 to 35 weeks after initiation of rHuEpo therapy, when hemoglobin concentration was 6.8 +/- 0.9 and 10.6 +/- 0.66 g/dl (mean +/- SD), respectively. The mean arterial pressure remained unchanged during this period (88 +/- 21 vs. 88 +/- 15 mm Hg). Echocardiographic study showed that rHuEpo treatment led to a decrease in left ventricular end-diastolic diameter (4.9 +/- 0.5 vs. 5.1 +/- 0.6 cm; P less than 0.03), left atrial diameter (3.22 +/- 0.30 vs. 3.43 +/- 0.33; P less than 0.03), and left ventricular mass index (109.8 +/- 30.6 vs. 133 +/- 30.8 g/m2; P less than 0.05). Left ventricular ejection volume decreased from 86 +/- 24 to 75 +/- 19 ml (P less than 0.03) and heart rate from 76 +/- 9 to 70 +/- 10 beats/min (P less than 0.05). Cardiac index decreased from 4715 +/- 700 to 3635 +/- 444 ml/min/m2 (P less than 0.01) and peripheral resistances rose from 1480 +/- 162 to 1943 +/- 250 dynes.sec.cm-5.m2 (P less than 0.01). Fractional ejection and mean circumferential fiber shortening remained unchanged. The treatment with rHuEpo did not change the aortic diameters.(ABSTRACT TRUNCATED AT 250 WORDS)