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维持性血液透析患者贫血及其相关因素分析
中文摘要

目的:横断面分析上海交通大学医学院附属新华医院血液净化部维持性血液透析(Maintenance hemodialysis,MHD)患者贫血达标状况,研究维持性血液透析患者血红蛋白((Hemoglobin,HGB)达标率及贫血程度的影响因素。探讨本中心使用促红细胞生成素(Erythropoietin, EPO)的患者是否存在促红细胞生成素抵抗(Erythropoiesis resistance),并试分析MHD患者对促红素反应性的影响因素。 方法:1)选择2017年10月20日至2017年11月19日期间,我院稳定血液透析(透析龄≥3个月并符合筛选条件)345例患者作为研究对象,收集登记的基本数据,包括人口统计学资料、原发病因、透析模式、药物治疗、实验室数据情况等。统计本院血红蛋白达标率,再根据血红蛋白是否达标(Hb≥1109/L)、贫血严重程度进行分组,比较各组MHD患者一般情况、药物治疗情况、血管通路、治疗模式、生化指标等因素。并利用多元logistics回归分析关于贫血达标的危险因素。 2)筛选符合条件并正接受重组促红细胞生成素治疗的患者300例,利用促红细胞生成素低反应性指数(Erythropoietin resistance index,ERI)研究MHD患者性别、药物治疗、治疗模式、治疗频率等各方面对EPO反应性的影响,并利用Pearson相关性分析及多元线性回归分析ERI的独相关因素。 结果:1)本院研究共纳入的345例MHD患者中,按Hb≥110 g/L为血红蛋白达标进行统计,Hb达标患者205名(占59.4%)。将患者按原发病分组,发病率前四位分别为原发性肾小球疾病170例(占49.28%),糖尿病肾病63例(占18.26%),高血压肾病62例(占17.97%),多囊肾20例(占5.80%)。其中自身免疫相关原发病平均血红蛋白水平最低(P=0.056)。按Hb是否达标比较患者年龄、透析龄、干体重、Kt/V、URR、血管通路、血清铁(Fe)、铁蛋白(SF)、透析前血清磷(P)、校正钙(Ca)、甲状旁腺素(PTH)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)等,差异无统计学意义(P>0.05);贫血达标组患者的男性比率、转铁蛋白饱和度(TSAT)达标率、杂合型透析模式(HD+HDF+HP)治疗率、前白蛋白、白蛋白(ALB)、中性粒细胞百分比(N%)、透前血清钾(K)、透前血清镁(Mg)、透前二氧化碳结合力(CO2CP)、血肌酐(Scr)均高于未达标组,超敏C反应蛋白(hsCRP)、碱性磷酸酶(ALP)低于未达标组,差异有统计学意义(P<0.05)。按照贫血程度分层比较重度贫血组、中度贫血组、轻度贫血组、达标组、超标组的男性比率、URR、 N%、血前白蛋白、ALB、ALP、K、Mg、血尿素氮(BUN)、PTH、hsCRP具有统计学差异,(P<0.05)。其中重度贫血的两例透析龄偏低,考虑与饮食习惯、毒素累积、透析充分性差有关。关于血红蛋白达标的多因素logistics回归结果显示女性患者、酸中毒、低镁血症、继发性甲状旁腺机能亢进、铁缺乏是影响MHD患者血红蛋白达标的独立危险因素。 2)排除未使用EPO治疗的45名患者,按照每周每千克体重EPO用量分组,结果提示MHD患者的EPO用量与血红蛋白达标率无明显相关,部分患者存在EPO抵抗的可能。分别对比不同性别、原发病、药物应用(静脉铁剂、口服铁剂、他汀类、ACEI类)、透析模式、血管通路、透析频率等对于ERI及EPO抵抗发生率的影响,除了性别、治疗频率外其他均无显著差异。但药物与ERI的关系需要更加严谨的临床前瞻性试验加以验证。透析频率(>2次/周)可以显著降低EPO抵抗发生率,另外杂合型透析模式(HD+HDF+HP)可以有效增加透析充分性,在保证小分子毒素被清除的基本上减少体内β 2-MG等大分子毒素的累积,但无直接证据可以改善EPO低反应性。关于ERI的Pearson相关分析提示:ERI与Kt/V、URR、hsCRP、HDL、β 2微球蛋白、校正钙水平呈正相关(r=0.202,r=0.238,r=0.152,r=0.245,r=0.154, r=0.153,P<0.05),与干体重、前白蛋白、LDL、TSAT呈负相关(r=-0.309,r=-0.216,r=-0.166,r=0.122,P<0.05)。而ERI与ALB、PTH、SF等无统计学意义。后将显著相关因素纳入多元线性回归模型,结果提示hsCRP、TSAT、LDL、HDL、Kt/V为ERI的独立相关变量(P<0.05)。 结论:本次研究中MHD患者的贫血治疗达标率为59.4%,高于目前国内一般水平。女性、酸中毒、透前电解质紊乱、继发性甲状旁腺机能亢进、铁缺乏均为为影响MHD患者血红蛋白达标的危险因素,而选择杂合式(HD+HDF+HP)透析模式可以提高血红蛋白水平。EPO治疗率为86.96%,EPO抵抗(ERI>2.5 IU/wk/㎏/g/L)发生率为9.00%。而hsCRP、 TSAT、LDL、HDL、Kt/V是ERI的独立相关因素。提高透析治疗频率(>2次/周)可以显著降低EPO抵抗发生率,而其他因素如原发病、透析模式等未发现与EPO反应性有关。另外女性MHD患者相比于男性患者更易发生贫血和EPO抵抗,是否绝经未见无明显影响。 关键字:维持性血液透析 血红蛋白 贫血 促红细胞生成素抵抗

英文摘要

Objective: Cross-sectional analysis of anaemia in maintenance hemodialysis patients in the Department of Blood Purification, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. To investigate the influencing factors of hemoglobin compliance rate and anemia level in maintenance hemodialysis patients. To investigate whether there is erythropoiesis-hyporesponsiveness in patients with erythropoietin (EPO) in our center, and to analyze the influencing factors of erythropoietin reactivity in MHD patients . Methods: 1)Select 345 patients with stable hemodialysis (dialysis age ≥ 3 months and meet the screening conditions) from October 20, 2017 to November 19, 2017 as the study object.Collecting the basic data of registration, including population Statistical data, cause disease, dialysis model, medication, laboratory data, etc. The hemoglobin compliance rate was calculated(Hb≥110g/L) and then grouped according to whether hemoglobin was up to standard(Hb≥110g/L) and the severity of anemia. The general conditions, drug treatment, vascular access, treatment modes, and biochemical indicators of each group of MHD patients were compared. And using multivariate logistic regression analysis of risk factors for anaemia compliance. 2)Select 300 patients who meet the conditions and are receiving recombinant erythropoietin, and use erythropoietin resistance index (ERI) as a tool.Researching the effect of gender, drug treatment, treatment mode, and treatment frequency on ERI and EPO resistance. The effects of EPO on responsiveness were analyzed using Pearson correlation analysis and multiple linear regression analysis of ERI independent factors. Results: 1) Among the 345 patients with MHD included in this study, Hb ≥ 110 g/L was used as the standard of hemoglobin compliance, and 205 patients (59.4%) were met with the standard. The patients were grouped according to the original disease. The incidence of primary glomerular disease was 170 cases (49.28%), diabetic nephropathy was 63 cases (18.26%), and hypertensive nephropathy was 62 cases (17.97%). Polycystic kidney disease in 20 cases (5.80%). The average hemoglobin level in autoimmune related primary disease was the lowest (P=0.056). Comparing the patient's age, dialysis age, dry weight, Kt/V, URR, vascular access, serum iron (Fe), ferritin (SF), pre-dialysis serum phosphorus (P), corrected calcium (Ca), thyroid Parathyroid hormone (PTH), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), etc., were not statistically significant (P>0.05). The ratio of males to patients with anemia in the anaemia group, TSAT compliance rate, heterozygous dialysis model (HD+HDF+HP) treatment rate, prealbumin, albumin (ALB), neutrophil percentage ( N%), pervasive serum potassium (K), prepermeant serum magnesium (Mg), permeate carbon dioxide binding capacity (CO2CP), and serum creatinine (Scr) were all higher than the non-compliance group, and high-sensitivity C-reactive protein (hsCRP), Alkaline phosphatase (ALP) was lower than the non-compliance group, the difference was statistically significant (P<0.05). According to the level of anemia, we compared the ratio of males in the severe anemia group, the moderate anemia group, the mild anemia group, the attainment group, and the over-standard group, URR, N%, pre-blood albumin, ALB, ALP, K, Mg, and blood urea nitrogen. (BUN), PTH, and hsCRP were statistically different (P<0.05). Two cases of severe anemia, with low dialysis age, were associated with dietary habits, toxin accumulation, and poor dialysis adequacy. The multivariate logistic regression analysis of hemoglobin attainment indicated that female patients, acidosis, hypomagnesemia, secondary hyperparathyroidism, and iron deficiency were independent risk factors affecting hemoglobin levels in MHD patients. 2)Excluding 45 patients not treated with EPO were grouped according to EPO dosage per kilogram of body weight per week. The results suggest that the dose of EPO in MHD patients is not significantly related to the hemoglobin compliance rate, and some patients may have EPO resistance. The effects of gender, primary disease, drug use (venous iron, oral iron, statins, ACEIs), dialysis model, vascular access, dialysis frequency, etc., on the incidence of ERI and EPO resistance, in addition to gender, treatment There were no significant differences outside the frequency. However, the relationship between drugs and ERI needs more rigorous clinical prospective trials to verify. The frequency of dialysis (>2 times per week) can significantly reduce the incidence of EPO resistance. In addition, the heterozygous dialysis model (HD+HDF+HP) can effectively increase the dialysis adequacy and substantially reduce the body of β2 in ensuring that the small molecule toxin is eliminated. -Accumulation of macromolecule toxins such as β2-MG, but there is no direct evidence to improve EPO low reactivity. Pearson correlation analysis of ERI suggested that ERI was positively correlated with Kt/V, URR, hsCRP, HDL, β2 microglobulin, and corrected calcium levels (r=0.202, r=0.238, r=0.152, r=0.245, r=0.154). (r=0.153, P<0.05), negatively correlated with dry weight, prealbumin, LDL and TSAT (r=-0.309, r=-0.216, r=-0.166, r=0.122, P<0.05). The ERI and ALB, PTH, SF, etc. were not statistically significant. After the significant correlation factors were included in the multiple linear regression model, the results suggested that hsCRP, TSAT, LDL, HDL, and Kt/V were independently related variables of ERI (P<0.05). Conclusion: The standard rate of anemia treatment in MHD patients was 59.4% in this study, which is higher than the current domestic general level. Females, acidosis, osmotic electrolyte imbalance, secondary hyperparathyroidism, and iron deficiency are all risk factors affecting hemoglobin levels in MHD patients, while heterozygous (HD+HDF+HP) dialysis mode can increase hemoglobin levels. . The rate of EPO treatment was 86.96%, and the incidence of EPO resistance (ERI>2.5 IU/wk/㎏/g/L) was 9.00%. HsCRP, TSAT, LDL, HDL, and Kt/V were independently related factors of ERI. Increasing the frequency of dialysis treatment (>2 times/week) can significantly reduce the incidence of EPO resistance, while other factors such as primary disease, dialysis model, etc. were not found to be related to EPO reactivity. In addition, women with MHD were more likely to suffer from anemia and EPO resistance than men, and there was no significant effect of menopause. KEY WORDS: maintenance hemodialysis, anemia, erythropoietin resistance index

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