Erythropoiesis and erythrocyte age distribution in hemodialysis patients undergoing erythropoietin therapy

Renal anemia is caused in part by a reduced life span of red blood cells (RBCs) and by reduced erythropoietin biosynthesis in the damaged kidney. The RBC age can be determined by density gradient centrifugation and estimation of cell-age-dependent enzyme activities, as aspartate aminotransferase. The RBC age distribution influences the median density (D50) of RBCs and the blood rheology in coherence with the hematocrit. In our study, the median density was determined by Percoll density gradient centrifugation in 18 healthy subjects (D50 = 1.0674 +/- 0.0016 g/ml) and in 14 hemodialysis patients (D50 = 1.0674 +/- 0.0016 g/ml in the course of recombinant human erythropoietin (rhEPO) therapy. During the first 4 weeks of therapy, a strong rejuvenation of RBCs was observed whereby the D50 reached a minimum after 2 weeks (D50 = 1.0655 +/- 0.0022 g/ml; p less than 0.05 vs. value before therapy) and a steady state after 4 weeks (D50 = 1.0658 +/- 0.0013 g/ml; p less than 0.1 vs. value before therapy). In 5 of the patients with elevated plasma parathyroid hormone (i-PTH) concentrations greater than 10 pmol/l, a significantly (p less than 0.05) reduced amount of younger RBCs (D50 = 1.0675 +/- 0.0016 g/ml) was observed in the first 2 weeks of rhEPO therapy as compared to patients with i-PTH less than 10 pmol/l (D50 = 1.0677 +/- 0.0019 g/ml). Thus, erythropoiesis in the early phase of rhEPO therapy is strongly influenced by elevated plasma i-PTH concentrations. Therefore, a gradual increase in rhEPO doses is preferable before therapy at elevated doses with an uncontrolled increase in RBC amount.     

促红细胞生成素与左旋卡尼汀对维持性血液透析患者营养状况的影响

目的　探讨促红细胞生成素 (EPO)与左旋卡尼汀对维持性血液透析 (MHD)患者营养状况的影响。方法　将 40例MHD患者随机分为A、B、C 3组 ,A组给以左旋卡尼汀 ,B组给以促红细胞生成素 ,C组以上两种药物合用 ,进行为期 3个月的随访 ,并监测人体学指标和血生化指标。结果　随访 3个月后 ,A组患者营养指标无明显变化 ,B组和C组患者营养指标有明显改善 (P <0 .0 1) ,C组与B组比较 ,营养状况改善更明显 (P <0 .0 5 )。结论　联合使用促红细胞生成素与左旋卡尼汀后MHD患者营养状况较单独使用红细胞生成素改善更加明显     

Relationship between resistance to erythropoietin and high anomalous hemoglobin levels in hemodialysis patients with beta-thalassemia minor

In dialysis patients beta-thalassemia is a cause of resistance to erythropoietin (EPO). The aim of the present study is to evaluate the relationship between the amount of circulating anomalous hemoglobin chain and EPO resistance in hemodialysis. Ten hemodialyzed patients with beta-thalassemia minor were studied. The mean hemoglobin level was 9.22 +/- 0.91 g/dl, the HbA2 ranging between 5.6 and 6.8%; the weekly EPO dose was 13,500 +/- 7,185 IU/week and significantly correlated with HbA2 (r = 0.965; p = 0.0001). When stratifying patients in two groups according to HbA2 level (LOW <6%, n = 4; HIGH >6%, n = 6; HbA2 levels, respectively, 5.7 +/- 0.1 and 6.4 +/- 0.3 g/dl, p = 0.002), it was evidenced that the need of EPO was 13,200 +/- 3,033 IU/week in LOW and 36,167 +/- 13,060 IU/week in HIGH (p < 0.001). The EPO Resistance Index in the two groups was 13.4 +/- 4.1 IU/kg BW/week/g Hb in LOW and 21.9 +/- 10.0 in HIGH (p < 0.05). No differences were evidenced between the two groups regarding age, dialysis, body weight, serum levels of urea nitrogen, creatinine, albumin, C-reactive protein, aluminum, ferritin, transferrin and parathyroid hormone. In conclusion, in patients with beta-thalassemia minor on chronic hemodialysis, the amount of anomalous hemoglobin chain directly correlate with EPO dose, strongly indicating the magnitude of resistance to erythropoietin.     

性别和年龄与脑动脉狭窄的相关性研究

目的探讨性别和年龄与脑动脉狭窄的关系。方法选择缺血性脑卒中患者565例,男性420例、女性145例、年龄<65岁276例、年龄≥65岁289例,比较不同性别、年龄患者脑动脉狭窄的情况。结果颅外动脉狭窄率高于颅内动脉(71.9%vs 63.0%,P<0.05)。男性颅内动脉狭窄率明显高于女性(65.5%vs 55.9%,P=0.039)。在年龄<65岁患者中,男性颅外动脉狭窄率与女性无明显差异(63.6%vs 52.5%,P=0.122),男性颅内动脉狭窄率高于女性(56.7%vs 39.0%,P=0.016);在年龄≥65岁患者中,男性颅外和颅内动脉狭窄率与女性无明显差异(84.7%vs 75.6%,P=0.064,74.9%vs 67.4%,P=0.195)。年龄与颅外和颅内动脉狭窄存在相关性(P<0.05),性别与颅外、颅内动脉狭窄无相关性(P>0.05)。结论不同性别和年龄脑动脉狭窄分布存在差异。男性可能更易罹患脑动脉狭窄,男性颅内动脉狭窄更常见。     

重组人促红细胞生成素治疗血液透析患者肾性贫血效果分析

目的采用促红细胞生成素抵抗指数(ERI)评价血液透析患者肾性贫血的治疗效果,并分析可能的影响因素。方法采用横断面研究方法,对2012年4月在四川大学华西医院血液透析中心行维持性血液透析的患者进行调查,按ERI指数分成3组:A组ERI<15,B组ERI 15～25,C组ERI>25。比较各组临床指标的差异,并通过相关性分析探讨ERI的影响因素。结果研究共纳入260例维持性血液透析患者,平均ERI为22.53±9.21。C组的超敏C反应蛋白(hs-CRP)、甲状旁腺激素(PTH)高于A、B组(P<0.05),而尿素清除指数(Kt/V)和转铁蛋白饱和度(TSAT)低于其他两组(P<0.05)。3组患者的白蛋白、血脂、铁蛋白差异无统计学意义。相关性分析显示,hs-CRP、PTH、Kt/V、TSAT是ERI升高的影响因素。结论促红细胞生成素治疗血液透析患者肾性贫血的效果受诸多因素影响,在调整药物剂量前应首先对相关因素进行评估和干预,以避免盲目增加药量而导致的副反应和治疗花费。     

Arterial hypertension in patients with chronic kidney insufficiency in hemodialysis with erythropoietin

The purpose of this study was to evaluate the effect of the partial correction of anaemia with recombinant human erythropoietin (rHuEPO) on the blood pressure (BP) of patients on chronic haemodialysis (HD). A group of 50 patients (26 men and 24 woman, mean age of 50 +/- 19.0 and range of 21 to 67) with basal levels of haemoglobin (Hb) less than or equal to 8 g/dl was evaluated before and during treatment with rHuEPO. Recombinant erythropoietin was started at 50 U/kh I.V. 3 times a week, immediately after each session of HD, for 4 weeks, and this dose was increased in steps of 25 U/kg until and Hb level of 12 g/dl or a maximum dose of 100 U/kg were reached. Before the administration of rHuEPO 33 patients (67.3%) were normotensives and 16 (32.6%) were hypertensives treated and well controlled. During the period of administration of rHuEPO 10 of the normotensives (30.3%) and 5 (31.3%) of the hypertensives patients showed an increase in the B.P. There was no correlation between the frequency of increase in B.P. and sex, age, length of time on HD and previous levels of B.P., but that frequency was higher in the patients with the lowest basal levels of haematocrit (Hct) and with the greatest increases in Hct (delta Hct). An immediate effect of I.V. administration of rHuE-PO on B.P. levels was not found. Finally we discuss the etiopathologic factors eventually responsible for the increase in BP and suggest some rules to be observed in the therapeutic use of rHuEPO.     

Association of nodular hyperplasia with resistance to cinacalcet therapy for secondary hyperparathyroidism in hemodialysis patients

There have been few long-term prospective studies investigating the effect of cinacalcet on secondary hyperparathyroidism with or without nodular hyperplasia. We examined whether the effect of cinacalcet on secondary hyperparathyroidism differed between patients with or without nodular hyperplasia. Stable hemodialysis patients with secondary hyperparathyroidism resistant to conventional treatment received cinacalcet for 12 months. Based on ultrasonography findings, patients were divided into group S (gland < 500 mm(3) without nodular hyperplasia) and group L (gland ≥ 500 mm(3) with nodular hyperplasia). Serum levels of intact parathyroid hormone, bone-specific alkaline phosphatase, osteocalcin, and cross-linked N-terminal telopeptide of type 1 collagen were measured. Thirty-one patients completed the study. The changes of parameters from the baseline did not differ significantly between the two groups after 6 months. However, the percentage reduction of each parameter was significantly smaller in group L compared with group S after 12 months. Nodular hyperplasia is associated with resistance to cinacalcet therapy in patients on chronic dialysis with secondary hyperparathyroidism.     

Key role of insulin resistance in vascular injury among hemodialysis patients

Insulin resistance prevails not only among diabetic patients but also among hypertensive and obese patients. The relationship between insulin resistance and cardiovascular diseases was investigated in hemodialysis (HD) patients. Eighty-one maintenance HD patients were enrolled. The homeostasis model assessment of insulin resistance (HOMA-IR) method was used to assess insulin resistance. The relationship of HOMA-IR with cardiovascular and all-cause events was assessed. Compared with nondiabetic patients (n = 55), diabetic patients (n = 26) showed higher HOMA-IR (2.5 +/- 0.3 vs 1.4 +/- 0.2, P < .05), lower ankle-brachial pressure index (ABI, 0.85 +/- 0.09 vs 1.12 +/- 0.02, P < .01), and shorter HD duration (3 +/- 1 vs 9 +/- 1 years, P < .01), although their body mass index was similar (22.3 +/- 0.5 vs 21.5 +/- 0.4 kg/m(2)). Nondiabetic patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (n = 36) had lower HOMA-IR (1.2 +/- 0.2 vs 1.8 +/- 0.4, P < .05) and higher ABI (1.18 +/- 0.02 vs 1.02 +/- 0.05, P < .01) than those without (n = 17). Cardiovascular events were less common in HD patients with normal HOMA-IR (P < .05) or ABI (P < .01). Our data indicate that 69% of diabetic and 27% of nondiabetic patients have HOMA-IR greater than 1.6, implying reduced insulin sensitivity in HD patients. The present results provide evidence that angiotensin inhibition improves insulin resistance, possibly preventing vascular injury in HD patients. Finally, our findings suggest that insulin resistance is prognostic of cardiovascular events in HD patients.     

Correction of copper deficiency improves erythropoietin unresponsiveness in hemodialysis patients with anemia

We have encountered five hemodialysis patients who had received enteral nutrition and recovered from erythropoietin-resistant anemia with neutropenia after the correction of copper deficiency. We reduced the required doses of recombinant human erythropoietin (rHuEPO) to maintain the target hematocrit levels and three patients were finally weaned from the rHuEPO therapy. Thus, copper deficiency is involved in erythropoietin-resistant anemia in hemodialysis patients.     

Association of HCMV specific IgG subclass antibody levels with gender and age

Infection with human cytomegalovirus (HCMV), a ubiquitously distributed herpesvirus, has been associated with human immune system aging. Especially total HCMV specific IgG antibody (AB) titres have been correlated with human frailty and mortality. The aim of this study was to further assess to which extent HCMV specific subclass AB titres differ between individuals and whether this is associated with age and gender.     

老年血液透析患者血压升高的机制及促红细胞生成素的影响

目的　探讨老年血液透析患者血压升高的机制以及基因重组促红细胞生成素(rHuEPO ,EPO)对维持性血液透析患者血管活性介质的影响。　方法　 5 2例老年血液透析患者 ,合并高血压者 2 3例 (HBP组 ) ,正常血压者 2 9例 (NBP组 )。检测血中血管活性介质 :内皮素 (ET)、肾素活性 (PRA)、醛固酮 (PA)、血管紧张素Ⅰ (AⅠ )、血管紧张素Ⅱ (AⅡ )、多巴胺 (DA)、肾上腺素 (E)和去甲肾上腺素 (NE)。NBP组中 15例静脉 1次注射EPO 30 0 0U(EPO组 ) ,14例作为对照 (NS组 )静脉注射生理盐水。均于注射后第 1、3、6、9、12、18、2 4、30、4 4h动态检测血中EPO和上述血管活性介质。　结果　 (1)与NBP组较比 ,HBP组DA (346 0 6± 137 12 )pmol/L、E (6 0 0 0 0± 4 36 36 )pmol/L和NE(4789 90± 1892 31)pmol/L明显增加 (P <0 0 5 ) ;(2 )与NS组相比 ,EPO组ET一过性升高 ,而DA、E和NE进行性升高 (P >0 0 5 )。　结论　老年血液透析患者血压升高和EPO引起的血压升高的机制可能与血中DA、E和NE增多有关。     

Influence of age and gender in Japanese patients with non-alcoholic steatohepatitis

Aim: Nonalcoholic steatohepatitis (NASH) is considered to be a manifestation of metabolic syndrome. Because prevalence and severity of metabolic syndrome are different according to ages, gender and ethnic group, it is speculated that the clinicopathological features of NASH may also vary in relation to these factors. The present study was performed to clarify the influence of age and gender on the development of Japanese NASH. Subjects: One hundred 93 biopsy-proven NASH patients (86 women and 107 men) were included in this cross-sectional study. The patients were separately analyzed by generation; a younger group (<55 years old) and an older group (>/=55 years old). These groups were compared for their clinical and histological features. Independent risk factors for advanced fibrosis were also analyzed. Results: Comparison of our younger and older groups showed that older patients had much more advanced fibrosis than the younger ones (advanced fibrosis: 23.8%; youngergroup vs. 54.3%; older group, P < 0.001). Women were predominant in the older group (23.8%; younger group vs. 67.4%; older group, P < 0.001). According to the multivariate analysis for risk factors for advanced fibrosis, age (P = 0.007) and BMI (P = 0.028) were independent predictors of advanced fibrosis in the younger group. In contrast, the absence of hyperlipidemia (P = 0.042) was the only significant independent predictor of advanced fibrosis in the older group. Gender was not a risk factor for the severity of NASH. Conclusions: Clinicians need to be aware of age- and gender-specific differences when assessing the characteristics of NASH, and the findings may be useful for prevention and treatment of this disease.