不同给药途径补铁对肾性贫血的疗效及促红细胞生成素用量的影响

目的:比较静脉和口服补铁纠正肾性贫血的疗效,以及对重组人促红细胞生成素(rHuEPO)用量的影响。方法:260例未达到贫血治疗靶目标的血液透析病人,随机分为静脉铁组和口服铁组,前者给予右旋糖酐铁100 mg,在透析中静脉输入,每周2次,5 wk后改为100 mg·2 wk~(-1),至12 wk。后者给予琥珀酸亚铁200 mg,po,tid,连续服用12 wk。结果:治疗12 wk后,静脉铁组(n=165)血红蛋白(Hb)增长(21±s 13)g·L~(-1),血细胞比容(Hct)增长0．07±0．03,血清铁蛋白(SF)增长(334±134)μg·L~(-1),运铁蛋白饱和度(TSAT)增长(9±6)%,均P＜0．01。口服铁组(n=84)中,Hb和Hct分别增长(14±27)g·L~(-1)和0．032±0．010,P＜0．01;而SF和TSAT无明显变化,P＞0．05。以上2组指标变化比较差异均有非常显著意义(P＜0．01)。静脉铁组rHuEPO用量为(6 530±2 234)IU·wk~(-1),显著少于口服铁组(8839±1922)IU·wk~(-1)(P＜0．01)。静脉铁组纠正贫血达标率为Hb达标73．9%和Hct达标78．8%,均高于口服铁组(Hb达标43%和Hct达标40%,P＜0．01)。静脉铁组的不良反应发生率为1．2%,口服铁组为6%。结论:静脉应用右旋糖酐铁比口服琥珀酸亚铁能够更安全、有效地纠正肾性贫血,并且可以显著减少rHuEPO的用量。     

静脉注射右旋糖酐铁优于口服琥珀酸亚铁治疗血液透析铁缺乏贫血

目的 :比较静脉铁剂与口服铁剂在治疗透析相关性贫血中的疗效。方法 :2 3例病人随机分入静脉铁剂组 (静脉组 )和口服铁剂组 (口服组 ) ,前者给予右旋糖酐铁 10 0mg ,在病人每次透析中经透析器的静脉端输入 ,直至完成总预计补铁量 (15 36±s2 5 4 )mg ,观察时间约 6～ 8wk ;后者给予琥珀酸亚铁 2 0 0mg ,po ,每日 3次 ,连续服用 8wk。 2组病人均同时使用促红细胞生成素治疗。结果 :静脉铁剂组治疗 8wk后 ,血红蛋白增长 (15± 12 )g·L- 1,红细胞比容增长 (4± 3) % ,血清铁蛋白增长 (330±15 8) μg·L- 1,而口服铁剂组三者分别为 (3± 11)g·L- 1,(0 .7± 2 .3) %和 (10 2± 2 2 4 ) μg·L- 1,差异有显著意义 (P <0 .0 5 ) ;静脉铁剂组的有效率为 5 5 % ,而口服铁剂组为 2 5 % ,两者差异有非常显著意义 (P<0 .0 1)。不良反应发生率静脉铁剂组是 9% ,口服铁剂组为 33%。结论 :静脉铁剂在治疗血液透析贫血病人铁缺乏时安全有效 ,并优于口服铁剂     

静脉用右旋糖酐铁经透析器清除的研究

目的:了解血液透析病人静脉滴注(静滴)右旋糖酐铁后,元素铁经透析器的清除情况。方法:6例稳定的维持性血液透析病人,均在透析h2开始静滴右旋糖酐铁100mg,时间大于30min。6例病人分别使用F6透析器和GFSplus12透析器,取新鲜透析液作为空白液,透析h1的废透析液作为对照液。测定空白液、对照液和静滴开始后至透析结束时所有的废透析液中铁的含量。结果:空白液和对照液的铁浓度分别为0. 82, (4. 3±s2. 6)μg·L-1;静脉输入右旋糖酐铁后,使用F6透析器和GFS plus12透析器时透析液中铁浓度分别为( 12±6 ),(15±7)μg·L-1,均高于对照液中铁浓度(P<0. 05,P<0. 01)。对铁的总清除量最大为2. 40mg,小于输入量的3%。结论:血液透析中使用F6透析器和GFSplus12透析器对右旋糖酐铁的清除很微量,利用率高。     

右旋糖酐氢氧化铁治疗肾性贫血的临床研究

目的比较静脉注射右旋糖酐氢氧化铁(科莫非)与口服多糖铁复合物(力蜚能)治疗维持性血液透析患者肾性贫血的疗效与安全性。方法 40例病情稳定的血液透析患者,规律透析2～3次/周。所有患者血红蛋白(Hb)60～100 g/L或红细胞压积(Hct)<30%,血清铁蛋白(SF)<200μg/L,转铁蛋白饱和度(TSAT)<30%,接受皮下注射重组人促红细胞生成素(rHuEPO)每周100～150 U/kg。将上述患者随机分为口服治疗组和静脉治疗组,每组20例,观察期为24周。口服组予多糖铁复合物150 mg/d。静脉组每次透析时静脉滴注右旋糖酐氢氧化铁100 mg,累计1 000 mg后每2周给予维持量100 mg。若患者的Hb达到110 g/L或Hct达到33%以上,则将rHuEPO减量以维持Hb及Hct水平。检测补铁前及补铁4、8、12、24周时患者Hb、Hct、SF以及TSAT水平。结果治疗后两组Hb、Hct、SF、TSAT均较治疗前有明显升高(P<0.05),静脉组Hb、Hct、SF、TSAT上升幅度均高于口服组(P<0.05)。治疗后24周静脉组rHuEPO用量较治疗前及口服组明显减少(P<0.05)。两组治疗前后肝功能差异无统计学意义。治疗后静脉组血清C反应蛋白高于治疗前及口服组,但仍在正常范围内。静脉组不良反应1例,口服组不良反应4例。结论静脉用右旋糖酐氢氧化铁治疗肾性贫血安全有效,不良反应少,且可减少rHuEPO用量。     

维持血液透析患者应用静脉铁剂的治疗效果观察

目的观察维持血液透析病人由规律口服铁剂改为应用静脉铁剂后EPO应用剂量、铁储备纠正及症状改善情况。方法选择维持血液透析病人(规律口服琥珀酸亚铁0.2mgTid治疗大于6个月)54例,停用口服铁剂予静脉铁剂(右旋糖酐铁)补铁治疗。静脉铁剂剂量根据患者每2个月Hb、SF、TSAT检测结果及时调整。比较治疗前及治疗后2、4、6个月患者Hb、SF、TSAT、EPO用量及肝肾功能动态变化、透析充分性、症状改善及不良反应情况。结果①治疗2个月后平均Hb上升5g/l,EPO用量减低15%,SF较前明显升高(P<0.05)。②转铁蛋白饱和度治疗6个月后有显著改善(P>0.05),EPO用量减低37%。肝肾功能治疗前后无显著差异(P>0.05)。③Kt/V无显著差异(P<0.05)。④贫血及消化道症状明显改善。⑤1例不良反应发生。结论规律应用静脉滴注右旋糖酐铁可以安全有效地减少长期血液透析病人rhEPO用量,改善铁储备及利用情况,提高患者生活质量。     

静脉补铁治疗维持性血液透析患者肾性贫血的疗效观察

目的观察静脉补充右旋糖酐铁治疗维持性血液透析患者铁缺乏的疗效和安全性,以及治疗过程中重组人促红细胞生成素(rHuEPO)用量的变化。方法选择23例接受rHuEPO和口服铁剂治疗3个月以上,但疗效欠佳的维持性血液透析患者,其血红蛋白(Hb)60~90g/L或红细胞压积(Hct)0.18~0.27,给予右旋糖酐铁静脉补铁治疗,共观察8周,分别于治疗前及治疗后8周检测血常规、血清铁蛋白(SF)、转铁蛋白饱和度(TSAT)等指标,并记录rHuEPO的用量及药物不良反应。结果右旋糖酐铁可以显著提高患者的Hb、Hct和SF、TSAT,同时可明显减少rHuEPO用量,并且临床未见严重不良反应。结论静脉补充右旋糖酐铁治疗维持性血液透析患者铁缺乏、纠正贫血是安全、有效的,同时可以减少rHuEPO的用量。     

慢性炎症状态对血液透析病人补铁治疗的影响

目的: 评价慢性炎症状态对血液透析病人静脉补铁后铁代谢指标改变的影响。方法: 62例血液透析病人根据C 反应蛋白(CRP)值,分为CRP高值组(n=28)和CRP低值组(n=34),所有病人静脉使用铁右旋糖酐复合物,每次100mg,每周2~3次,共4wk,总剂量1 000mg。检测治疗前后血红蛋白、血细胞比容、血清铁蛋白(SF)、运铁蛋白饱和度(TSAT)、血清总铁结合力(TIBC)及CRP。结果:治疗后CRP高值组SF(945±s329)μg·L-1,明显高于CRP低值组(629±234)μg·L-1 (P<0. 01)。CRP高值组治疗后TIBC下降,显著高于CRP低值组(P<0. 01)。CRP与SF净增加值相关(r=0.36,P<0. 01),治疗后CRP高值组TSAT和SF呈正相关(r=0.51,P<0. 01 )。结论:慢性炎症状态下的血液透析病人可能更易出现高铁蛋白血症,而且对铁剂的治疗反应相对较差,部分原因可能与铁阻滞有关。     

间隔补铁治疗农村小儿缺铁性贫血临床分析

目的探讨间隔补铁治疗小儿缺铁性贫血的临床意义。方法将98例缺铁性贫血的小儿随机分为观察组和对照相。经12周补铁治疗,以血红蛋白(Hb)、血清铁蛋白(SF)作为评价治疗效果的血液学指标,并观察不同补铁方式的不良反应发生情况。结果两组病例在治疗后Hb、SF值交有不同程度的上升,与治疗前相比,有显著性差异(P<0.01)。治疗后Hb值无差异(P>0.05);SF值明显低于对照组(P<0.01)。副作用明显减少。结论间隔补铁在纠正贫血上与每日补铁同样有效且副作用少,在增加铁贮备上不如每日补铁明显。     

静脉使用蔗糖铁与口服铁治疗肾性贫血对照研究

目的:探讨静脉应用蔗糖铁治疗血液透析(HD)患者肾性贫血的有效性和安全性。方法:选择2007~2009年广州市中西医结合医院MHD患者30例,采用前瞻性随机对照研究,随机分为2组,观察各组用药前后血红蛋白(Hb)浓度,红细胞压积(Hct),转铁蛋白饱和度(TSAT),血清铁蛋白(SF)等疗效指标,并监测不良反应。结果:用药10周后,静脉补铁组Hb、Hct、SF水平与用药前相比均明显升高(P<0.01),优于口服补铁组,口服补铁治疗对MHD患者贫血疗效有限,治疗前后对比无统计学意义(P>0.05)。结论:静脉补铁不仅能及时有效的补充肾性贫血患者所需铁,使贫血状况改善,不良反应少,可安全应用。     

静脉滴注右旋糖酐铁注射液治疗慢性肾功能不全伴肾性贫血的临床疗效

目的观察静脉滴注(静滴)右旋糖酐铁注射液治疗慢性肾功能不全伴缺铁性贫血的疗效及安全性。方法103例慢性肾功能不全伴贫血患者,随机分为静滴组和肌注组。静滴组用进口右旋糖酐铁注射液100mg溶于100mLNS,ivgtt,每周2次;肌注组用国产右旋糖酐铁注射液100mg,im,每周2次,疗程均10wk。观察治疗前后红细胞计数(RBC)、血红蛋白(Hb)、血细胞比容(Hct)、血清铁蛋白(SF)、转铁蛋白饱和度(TSAT)、肝肾功能及药物不良反应。结果65例患者完成本研究,其中静滴组30例,肌注组35例。静滴组不良反应发生率为6.0%,低于肌注组(18.9%),P<0.01。治疗10wk后,2组贫血症状均有明显改善。静滴组SF、TSAT、Hb、Hct分别为(516.8±68.8)μg·L-1、(34.5±7.2)%、(88.8±14.4)g·L-1、(27.2±3.2)%;肌注组分别为(426±88.7)μg·L-1、(30.2±5.8)%、(79.0±11.4)g·L-1、(24.9±3.1)%,2组相比差异有统计学意义(P<0.05或P<0.01)。结论静滴右旋糖酐铁注射液治疗慢性肾功能不全伴缺铁性贫血是有效、安全的。     

静脉用蔗糖铁治疗腹膜透析患者肾性贫血25例疗效观察

目的探讨持续性非卧床腹膜透析患者应用静脉补铁纠正肾性贫血的临床疗效。方法选择2010年3月至2011年3月收治的非卧床持续性腹膜透析的患者50例,随机分为静脉补铁组(静脉组)和口服补铁组(口服组)各25例。两组患者均给予促红细胞生成素(EPO)3 000U/次,皮下注射,每周2次,口服叶酸片30 mg/d。在此基础上静脉补铁组给予蔗糖铁注射剂(森铁能),采用分次输入的方法;口服补铁组给予琥珀酸亚铁(速力菲)0.3克/次,3次/d。观察两组患者血红蛋白(Hb)、红细胞数(RBC)、红细胞压积(HCT)、血清铁蛋白(SF),并计算出转铁蛋白饱和度(TSAT)。结果两组患者在治疗后贫血均有改善,但静脉组改善情况明显优于口服组,两组比较差异有统计学意义(P<0.05)。结论促红细胞生成素治疗持续性非卧床腹膜透析患者贫血,通过静脉补铁较口服补铁能更好地纠正贫血,且能明显提高患者的生活质量。     

Single-dose pharmacokinetics of sodium ferric gluconate complex in iron-deficient subjects

STUDY OBJECTIVES: To determine the single-dose pharmacokinetics of intravenous sodium ferric gluconate complex in sucrose injection (SFGC) in iron-deficient human volunteers, and to assess iron transport. DESIGN: Open-label, randomized study. SETTING: Clinical research facility. SUBJECTS: Fourteen iron-deficient men and women. INTERVENTIONS: Subjects were randomized to receive a single intravenous dose of either SFGC 62.5 mg administered over 30 minutes or SFGC 125 mg over 60 minutes. Five days later, the same subjects were rerandomized to receive a second intravenous dose of SFGC, either 62.5 mg administered over 4 minutes or 125 mg over 7 minutes. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected at predefined times before, during, and up to 72 hours after the infusion to determine the single-dose pharmacokinetics of SFGC. Assays were performed for both total iron and transferrin-bound iron, from which drug-bound iron could be calculated. Urine was collected over 24 hours before dosing and for 24 hours after the start of infusion to determine the renal elimination of iron. Clearance of SFGC from serum was rapid and far exceeded rates reported for iron dextran. Pharmacokinetic parameters were unaffected by dose or infusion rate. Serum iron derived from SFGC did not exceed the binding capacity of transferrin. Serum iron from SFGC became rapidly available (< 24 hrs) as transferrin-bound iron, but only after passage through another compartment, presumably the reticuloendothelial system (RES). At least 80% of the administered iron was transported to bone marrow within 24 hours after infusion. CONCLUSIONS: Iron derived from SFGC appears to be rapidly transferred to a bioavailable iron compartment as transferrin-bound iron after digestion in the RES. At the doses administered in this study, liberation of potentially toxic, free iron was not detectable.     

Comparison of oxidative stress markers after intravenous administration of iron dextran, sodium ferric gluconate, and iron sucrose in patients undergoing hemodialysis

STUDY OBJECTIVE: To compare non-transferrin-bound iron and markers of oxidative stress after single intravenous doses of iron dextran, sodium ferric gluconate, and iron sucrose. DESIGN: Prospective, open-label, crossover study. SETTING: University-affiliated general clinical research center. PATIENTS: Twelve ambulatory patients undergoing hemodialysis. INTERVENTION: Patients received 100 mg of intravenous iron dextran, sodium ferric gluconate, and iron sucrose in random sequence, with a 2-week washout period between treatments. MEASUREMENTS AND MAIN RESULTS: Serum samples for transferrin saturation, non-transferrin-bound iron, and malondialdehyde (MDA; marker of lipid peroxidation) were obtained before (baseline) and 30, 60, 120, and 360 minutes and 2 weeks after each iron infusion. A serum sample for hemeoxygenase-1 (HO-1) RNA was obtained at baseline and 360 minutes after infusion. Non-transferrin-bound iron values were significantly higher 30 minutes after administration of sodium ferric gluconate and iron sucrose compared with iron dextran (mean +/- SEM 10.1 +/- 2.2, 3.8 +/- 0.8, and 0.23 +/-0.1 microM, respectively, p<0.001 for sodium ferric gluconate vs iron dextran, p = 0.002 for iron sucrose vs iron dextran). A significant positive correlation was noted between transferrin saturation and the presence of non-transferrin-bound iron for sodium ferric gluconate and iron sucrose (r2 = 0.37 and 0.45, respectively, p<0.001) but not for iron dextran (r2 = 0.09). After sodium ferric gluconate, significantly more samples showed increases in MDA levels from baseline compared with iron sucrose and iron dextran (p = 0.006); these increased levels were associated with the presence of non-transferrin-bound iron, baseline transferrin saturation above 30%, baseline transferrin levels below 180 mg/dl, and ferritin levels above 500 ng/ml (p<0.05). However, only a transferrin level below 180 mg/dl was independently associated (odds ratio 4.8, 95% confidence interval 1.2-15.3). CONCLUSION: Iron sucrose and sodium ferric gluconate were associated with greater non-transferrin-bound iron appearance compared with iron dextran. However, only sodium ferric gluconate showed significant increases in lipid peroxidation. The relationship between non-transferrin-bound iron from intravenous iron and oxidative stress warrants further exploration.     

Cefotaxime disposition pharmacokinetics during peritoneal dialysis

The pharmacokinetics of cefotaxime and its main metabolite des-acetyl-cefotaxime were studied after a single 1000 mg intravenous dose in 8 patients with end stage renal disease during peritoneal dialysis. Pharmacokinetic parameters were determined by iterative non-linear least squares regression analysis of plasma and dialysis fluid drug concentration curves. Biological half-life of cefotaxime ranged from 2.3 to 8.2 hours and total plasma clearance from 11 to 103 ml/min. (0.11 to 1.7 ml/min/kg b.wt). Only 1.4% to 4.2% of the intravenous dose of cefotaxime was distributed to the dialysis fluid. We conclude that the dosage of cefotaxime to uraemic patients adjusted to the renal function needs no further adjustment during peritoneal dialysis.     

Pharmacokinetics of ornidazole in patients with renal insufficiency; influence of haemodialysis and peritoneal dialysis.

The pharmacokinetics of ornidazole (Tiberal) was studied after intravenous administration of a single 500 mg dose in eight patients with advanced chronic renal failure (ACRF) (creatinine clearance 2-16 ml/min), in seven patients treated by haemodialysis (residual renal creatinine clearance 0-5 ml/min) and in five patients treated by continuous ambulatory peritoneal dialysis (CAPD) (residual renal creatinine clearance 0-6 ml/min). In ACRF patients, the half-life of ornidazole was 10.8 +/- 1.4 h, the total plasma clearance 46.3 +/- 2.3 ml/min and the volume of distribution 0.73 +/- 0.06 l/kg. During haemodialysis, ornidazole was partly removed: the dialyser extraction ratio was 42 +/- 5% and the dialysis clearance 64 +/- 7 ml/min. During CAPD, peritoneal excretion was low: the dialysis clearance was 3.0 +/- 0.4 ml/min and in 48 h 6.0 +/- 1.1% of the administered dose was found in the peritoneal fluids. In these patients, the half-life of ornidazole was 11.8 +/- 0.8 h and total plasma clearance was 48.3 +/- 5.5 ml/min, values which were close to those determined in non dialysed patients. In patients with end-stage renal disease, the half-life of ornidazole is comparable to that of subjects with normal renal function. This is due to the predominantly extra-renal elimination of the drug. Therefore, there is no need to modify the usual dosage of ornidazole for these patients. Because of the large elimination of the drug during haemodialysis it is necessary to administer the drug after the dialysis session.     

Safe administration of iron sucrose in a patient with a previous hypersensitivity reaction to ferric gluconate

A 67-year-old woman with iron deficiency anemia required parenteral iron therapy and was treated with intravenous ferric gluconate. She tolerated the first dose, but after the second dose, she developed a tingling feeling all over her body, along with swelling in her hands and feet, and a rash with hives over most of her body. It was thought that she had likely experienced a hypersensitivity reaction to ferric gluconate. The decision was made to continue therapy; however, two modifications were made. The patient was given dexamethasone, diphenhydramine, and ibuprofen 1 hour before administering the third dose, and the infusion time was prolonged by 1 hour. Approximately 45 minutes after the infusion was completed, the patient developed hives on her arms and legs. At the patient's next clinic visit, it was decided that continuation of parenteral iron repletion was necessary, and the decision was made to attempt a challenge with iron sucrose. The patient was given dexamethasone 8 mg to be taken the night before and the morning of treatment. She successfully completed the iron repletion therapy with iron sucrose. Three parenteral iron products are available in the United States: iron dextran, sodium ferric gluconate complex, and iron sucrose. Iron dextran, the oldest of these products, carries the highest risk for hypersensitivity reactions. Available data suggest that either iron sucrose or ferric gluconate can be safely administered to patients with known hypersensitivity to iron dextran. Our patient's experience implies that it may be possible to safely administer iron sucrose to a patient with hypersensitivity to ferric gluconate. This finding has clinical implications and warrants confirmation in a larger population.     

右旋糖酐铁治疗血液透析患者重度肾性贫血

目的:观察右旋糖酐铁注射液治疗维持性血液透析(血透)患者肾性贫血的疗效。方法:46例维持性血透患者,每周血液透析3次,每次4h。随机分为注射右旋糖酐氢氧化铁组(21例)与口服琥珀酸亚铁组(25例),检测治疗前后血清铁指标、红细胞相关指标及生化指标。结果:10次血透后两组Hb,Hct,血清铁蛋白(SF)与转铁蛋白饱和度(TSAT)均较治疗前显著升高,且静脉组明显高于口服组(P<0．01)。结论:静脉注射右旋糖酐氢氧化铁可有效纠正维持性血透患者的铁缺乏、提高铁利用率及重组红细胞生成素的治疗效果。     

促红细胞生成素联合静脉铁剂治疗肾性贫血的疗效分析

目的观察并比较静脉注射科莫非(右旋糖酐氢氧化铁)联合促红细胞生成素治疗维持性血液透析(HD)患者铁缺乏的临床疗效。方法采用前瞻性、随机对照研究。选择44例慢性肾衰竭维持性HD患者,随机分为静脉注射右旋糖酐氢氧化铁组(静脉组)与口服琥珀酸亚铁组(口服组),静脉组21例,口服组23例,总疗程8周。检测治疗前后血清铁、红细胞相关指标及生化指标,观察疗效及促红细胞生成素的用量。结果共40例完成本研究,静脉组20例,口服组20例,两组患者年龄、性别、族别、维持透析时间、贫血程度、血清铁指标及基因重组红细胞生成素(rHuEPO)用量无显著性差异;治疗8周后贫血均有明显改善,静脉组血红蛋白(Hb)上升(61.45±25.58)%,红细胞压积(Hct)上升(67.22±31.66)%,口服组Hb上升(31.77±13.37)%,Hct上升(34.41±21.81)%,静脉组显著高于口服组(P<0.001);静脉组血清铁蛋白(SF)上升(272.38±502.54)%,口服组上升(186.78±304.55)%,静脉组转铁蛋白饱和度(TSAT)上升(45.6±33.6)%,口服组上升(11.4±12.11)%,静脉组明显高与口服组(P<0.001);静脉组rHuEPO的用量(7150.00±1565.25),口服组rHuEPO的用量(10600.00±2521.49),rHuEPO的用量静脉组低于口服组(P<0.001);治疗8周后两组血清白蛋白升高,静脉组血肌酐下降,其他指标无改变。结论促红细胞生成素联合静脉铁剂治疗肾性贫血的疗效优于口服组,且节省促红细胞生成素的用量,减少治疗费用,适合维持性血液透析(HD)患者铁缺乏的长期补铁的途径。