Leehey David J, Palubiak David J, Chebrolu Srivasa, Agarwal Rajiv
Division of Nephrology, Department of Medicine, Loyola University School of Medicine and Edward Hines Jr VA Medical Center, Hines, IL 60141, USA.
Nephrol Dial Transplant. 2005 Jan;20(1):135-40. doi: 10.1093/ndt/gfh565. Epub 2004 Nov 2.
Intravenous (i.v) iron is widely used to treat anaemia in patients with chronic kidney disease (CKD). Although beneficial and usually well tolerated, concerns have been raised about its ability to cause oxidative stress and renal injury.
To determine if i.v. iron causes oxidative stress [as assessed by plasma and urine malondialdehye (MDA)] and/or renal injury (as assessed by urinary albumin, total protein and enzymuria), we conducted a prospective, four-way randomized crossover, blinded end-point trial in eight patients with CKD. Two widely used doses of sodium ferric gluconate (125 mg infused over 1 h and 250 mg infused over 2 h) were given with or without the antioxidant N-acetylcysteine (NAC), resulting in four treatment dose-antioxidant/placebo combinations in each patient. Transferrin saturation was measured with urea polyacrylamide gel electrophoresis, MDA by high performance liquid chromatography, and albuminuria and proteinuria by standard clinical methods. Enzymuria was assessed by measurement of N-acetyl-beta-D-glucosaminidase (NAG) excretion by colorimetric assay.
I.v. ferric gluconate infusion at both doses resulted in a marked increase in transferrin saturation and a significant increase in plasma MDA levels. Urinary MDA levels also increased at the higher dose of iron. There was no evidence of acute renal injury, as assessed by albuminuria, proteinuria or enzymuria. Pre-treatment with NAC had no effect on oxidative stress or the above urinary parameters.
I.v. ferric gluconate caused oxidative stress (as reflected by increased MDA), but this was not associated with biochemical manifestations of acute renal injury.
静脉注射铁剂被广泛用于治疗慢性肾脏病（CKD）患者的贫血。尽管其有益且通常耐受性良好，但人们对其引发氧化应激和肾损伤的能力表示担忧。
为确定静脉注射铁剂是否会导致氧化应激（通过血浆和尿液丙二醛（MDA）评估）和/或肾损伤（通过尿白蛋白、总蛋白和酶尿评估），我们对8例CKD患者进行了一项前瞻性、四组随机交叉、盲终点试验。给予两种广泛使用的葡萄糖酸铁钠剂量（1小时内输注125毫克和2小时内输注250毫克），同时给予或不给予抗氧化剂N-乙酰半胱氨酸（NAC），每位患者产生四种治疗剂量-抗氧化剂/安慰剂组合。通过尿素聚丙烯酰胺凝胶电泳测量转铁蛋白饱和度，通过高效液相色谱法测量MDA，通过标准临床方法测量白蛋白尿和蛋白尿。通过比色法测量N-乙酰-β-D-氨基葡萄糖苷酶（NAG）排泄来评估酶尿。
两种剂量的静脉注射葡萄糖酸铁均导致转铁蛋白饱和度显著增加，血浆MDA水平显著升高。较高剂量铁剂时尿MDA水平也升高。通过白蛋白尿、蛋白尿或酶尿评估，没有急性肾损伤的证据。NAC预处理对氧化应激或上述尿液参数没有影响。
静脉注射葡萄糖酸铁会导致氧化应激（表现为MDA增加），但这与急性肾损伤的生化表现无关。
