【摘要】目的观察硫代硫酸钠联合血液灌流对维持性血液透析(maintenance hemodialysis,MHD)患者顽固性皮肤瘙痒疗效及氧化应激状态的影响。方法选取2019 年1 月~2020 年12 月在上海市闸北区中心医院血液透析室行血液透析伴顽固性瘙痒患者70 例,随机分为3 组,分别为A 组(硫代硫酸钠治疗组)、B 组(血液灌流治疗组)、C 组(硫代硫酸钠联合血液灌流治疗组)。A 组患者每周血液透析3 次,每次透析下机前静脉推注硫代硫酸钠3.2g;B 组每周血液透析2 次,血液透析联合血液灌流1 次;C 组在B 组基础上每次透析下机前静脉推注硫代硫酸钠3.2g,持续3 月。检测治疗前和治疗3 月后血肌酐(Scr)、尿素氮(BUN)、血钙(Ca)、血磷(P)、β2微球蛋白(β2-MG)、甲状旁腺激素(PTH)、C 反应蛋白(CRP)、谷胱甘肽过氧化物酶(GSHPx)、超氧化物歧化酶(SOD)、丙二醛(MDA)指标,用匹斯堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)、视觉模拟评分法(visual analogue scale,VAS)对患者治疗前和治疗3 月后进行评分,并进行疗效及安全性评估。结果治疗3 月后,B 组与C 组血P、β2-MG、PTH 水平低于治疗前和A 组(B 组与C 组血P 的t 值分别为: 2.829, 4.226;P 值分别为: 0.010,<0.001;组间F值=3.191, P=0.041。B 组与C 组β2-MG 的t 值分别为: 2.363, 2.575;P 值分别为: 0.027, 0.017;组间F 值=4.658, P=0.013。B 组与C 组PTH 的t 值分别为: 2.715, 5.856;P 值分别为: 0.008, <0.001;组间F值=13.738, P<0.001);A组与C组的GSHPx、SOD水平均高于治疗前和同期B组(A组与C组GSHPx 的t值分别为: -2.247, -5.387;P值分别为: 0.035, <0.001;组间F值=15.577, P<0.001。A组与C组SOD的t值分别为: -2.300, -5.122;P值分别为:0.031,<0.001;组间F值=8.308, P=0.001);MDA水平明显下降(A组与C组MDA比较的t值分别为: 5.630, 7.904;P值均<0.001;组间F值=26.116, P<0.001)。治疗3月后,3组 患者的PSQI 评分、VAS 评分低于同组治疗前(3 组PSQI 评分的t 值分别为:4.739,4.761,8.803;P 值均<0.001。3组VAS评分的t值分别为: 15.087, 11.682, 17.310;P值均<0.001),C组的PSQI评分、VAS评分低于同期A组和B组(PSQI、VAS 评分的F值分别为: 15.049, 8.670;P值均<0.001)。治疗3月后,A组、B组、C组有效率分别为: 54.2%、47.8%、78.3%,3 组间比较差异存在统计学意义(χ2=4.956,P =0.026)。结论硫代硫酸钠联合血液灌流对MHD 患者顽固性皮肤瘙痒安全有效。硫代硫酸钠具有抗氧化作用,可能有助于缓解尿毒症性皮肤瘙痒。
【Abstract】Objective To observe the effect of sodium thiosulfate combined with hemoperfusion on refractory pruritus and oxidative stress in maintenance hemodialysis (MHD) patients. Methods A total of 70 MHD patients with refractory pruritus treated in the Hemodialysis Center, Shanghai Jing’an District Zhabei Central Hospital during January 2019 to December 2020 were enrolled in this study. They were randomly divided into three groups: group A (sodium thiosulfate group), group B (hemoperfusion group) and group C (sodium thiosulfate combined with hemoperfusion group). Patients in group A received hemodialysis three times a week, and 3.2g sodium thiosulfate was intravenously injected before every dialysis; those in group B received hemodialysis twice a week and hemodialysis combined with hemoperfusion once a week; those in group C used the dialysis protocols in group B as well as intravenous 3.2g sodium thiosulfate before every dialysis for 3 months. Serum creatinine (SCR), urea nitrogen (BUN), calcium (Ca), phosphorus (P), β2-micro-globulin (β2-MG), parathyroid hormone (PTH), C-reactive protein (CRP), glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured before and after 3 months treatment. Pittsburgh sleep quality index (PSQI) and visual analogue scale (VAS) were used before and after 3 months treatment to evaluate the efficacy and safety of the treatment. Results Serum P, β2-MG and PTH in group B and group C were lower after the treatment than those before the treatment, and were lower than those in group A after the treatment (Serum P, in group B and group C: t=2.829 and 4.226, P=0.010 and <0.001; between group B and group C: F=3.191 and P=0.041. Serum β2-MG, in group B and group C: t=2.363 and 2.575, P=0.027 and 0.017; between group B and group C: F=4.658 and P=0.013. Serum PTH, in group B and group C: t=2.715 and 5.856, P=0.008 and <0.001; between group B and group C: F=13.738 and P<0.001). Serum GSHPx and SOD in group A and group C were higher after the treatment than those before the treatment, and were higher than those in group B during the same period (Serum GSHPx, in group A and group C: t=-2.247 and - 5.387, P=0.035 and <0.001; between group A and group C: F=15.577 and P<0.001. Serum SOD, in group A and group C: t=-2.300 and -5.122, P=0.031 and <0.001; between group A and group C: F=8.308 and P=0.001). Serum MDA decreased significantly (in group A and group C: t=5.630 and 7.904, P<0.001; between group A and group C: F=26.116 and P<0.001). PSQI score and VAS score lowered after 3 months treatment compared to those before treatment in the three groups (PSQI score in groups A, B and C: t=4.739, 4.761 and 8.803 respectively, P<0.001; VAS score in groups A, B and C: t=15.087, 11.682 and 17.310 respectively, P<0. 001). PSQI and VAS scores lowered more in group C than in group A and group B during the same period (For PSQI score and VAS score: F=15.049 and 8.670, P<0.001). After 3 months treatment, the effective rates were 54.2%, 47.8% and 78.3% in group A, group B and group C, respectively, higher in group C than in groups A and B (χ2=4.956, P=0.026). Conclusions Sodium thiosulfate combined with hemoperfusion was safe and effective for MHD patients with refractory pruritus. Sodium thiosulfate has antioxidant effect, which may alleviate uremic pruritus.
[1] Mathur VS, Lindbe J, Gemain M, et al. A longitudinal study of uremic pruritus in hemodialysis patients[J]. Clin J Am Soc Nephml, 2010,5(8): 1410-1419.
[2] Combs SA, Teixeria JP, Germain MJ , et al. Pruritus in kidney disease[J]. Semin Nephrol, 2015, 35(4): 383-391.
[3] Elizabeth Simonsen , Paul Komenda , Blake Lerner, et al. Treatment of Uremic Pruritus: A Systematic Review[J]. Am J Kidney Dis. 2017; 70(5): 638-655.
[4] 胡小红,陈揭剑,梅长林. 尿毒症瘙痒发病机制与治疗进展[J]. 中华肾脏病杂志,2013,29(11): 866-869.
[5] 沈静,张琳,常艳微等.透析疗法治疗尿毒症性皮肤瘙痒症的研究进展[J]. 辽宁中医杂志,2018,45(6):1324-1326.
[6] 唐倩,蒋先淑,李志勇. 血液透析联合血液灌流与HDF治疗尿毒症患者皮肤瘙痒的Meta分析[J]. 重庆医学,2016,45(18):2522-2525.
[7] 杜雯,管海英,商鼎. 硫代硫酸钠应用于钙化防御的研究进展[J]. 上海医学, 2021,42(5):20-23.
[8] 吴红,肖跃飞.硫代硫酸钠治疗尿毒症皮肤瘙痒的临床观察[J]. 中国血液净化,2020,19(2):92-94,102.
[9] 刘音,赵彬,刘丽芳等. 硫代硫酸钠在血液透析患者难治性皮肤瘙痒症中的临床应用观察[J]. 临床肾脏病杂志,2020,20(3):194-197.
[10] Yu-Huan Song, Si-Yang Wang, Jia-Hui Lang, et al. Therapeutic effect of intravenous sodium thiosulfate for uremic pruritus in hemodialysis patients[J]. Renal
Failure, 2020, 42( 1), 987–993.
[11] WANG G, WANG K. The Ca2+ Permeable Cation Transient Receptor Potential TRPV3 Channel: An Emerging Pivotal Target for Itch and Skin Diseases[J].Mol Pharmacol, 2017, 92(3): 193-200.
[12] Wen-Hong Li, Yu-Min Yin, Hao Chen, et al. Curative effect of neutral macroporous resin hemoperfusion on treating hemodialysis patients with refractory uremic pruritus[J]. Medicine, 2017, 96(12): 1-6.
[13] 陈娟娟,刘素贞,杨义芳等. 血液灌流联合高通量血液透析对尿毒症性皮肤瘙痒的疗效及其对患者钙磷代谢和肾功能的影响[J]. 中国医学前沿杂志(电子版),2021,13(2):89-92.
[14] Ji-Won Min, Su-Hyun Kim, Young Ok Kim, et al. Comparison of uremic pruritus between patients undergoing hemodialysis and peritoneal dialysis[J]. Kidney Research and Clinical Practice, 35(2):107-113.