川黄1号方对慢性肾脏病3期患者尿IL-18及Kim-1的影响
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摘要
目的:观察川黄1号方对慢性肾脏病(chronic kidney disease,CKD)3期患者尿液中急性肾损伤标志物白介素-18(IL-18)及肾损伤分子-1(Kim-1)的影响。方法:纳入66例CKD 3期患者,随机分为川黄1号方组(治疗组)及氯沙坦片组(对照组),每组各33例;同时随机纳入20例健康志愿者作为对照。两组患者除给予基础治疗外,治疗组予川黄1号方汤剂口服,对照组予氯沙坦片口服,治疗周期均为24周。比较两组患者治疗前后的血清肌酐(Scr)、尿素氮(BUN)、估算肾小球滤过率(e GFR,MDRD公式计算)、尿酸(UA)、尿IL-18、尿Kim-1、24 h尿蛋白定量(24 h U-pro)水平的变化,同时对比健康志愿者与CKD 3期患者尿IL-18、尿Kim-1的水平。结果:1与健康志愿者比较,CKD患者的尿IL-18、Kim-1水平均显著升高(P<0.01)。2治疗后,治疗组患者的e GFR明显升高(P<0.05),Scr、BUN水平明显降低(P<0.05,P<0.01),对照组患者的UA水平明显降低(P<0.05);且治疗组患者的e GFR、UA水平高于对照组(P<0.05),Scr、BUN水平低于对照组(P<0.05,P<0.01)。3治疗后,两组患者的24 h U-pro、尿IL-18、尿Kim-1水平较治疗前均明显降低(P<0.05,P<0.01),且对照组患者的24 h U-pro水平低于治疗组(P<0.05),治疗组患者的尿IL-18水平低于对照组(P<0.05)。结论:1急性肾损伤标志物尿IL-18、Kim-1可能有助于CKD肾损伤的早期发现及疗效判定;2川黄1号方能有效保护3期CKD患者的肾功能,具有较好的临床推广应用前景。
Objective: To observe the influence of "Chuanhuang Recipe No. 1 "( CHR) on the level of urinary interleukin-18( IL-18) and kidney injury molecule-1( Kim-1) in patients with chronic kidney disease( CKD) at phase 3.Methods: Sixty-six patients with CKD at phase 3 were selected and randomly divided into the CHR group( treatment group)and the losartan potassium group( control group) with 33 cases in each group. Meanwhile,20 healthy volunteers were involved as control. All the patients were treated with the conventional medicine,and the patients in the treatment group were treated with CHR and the patients in the control group were treated with losartan tablet in addition,with a course of 24 weeks. The levels of serum creatinine( Scr),blood urea nitrogen( BUN),estimated glomerular filtration rate( e GFR),serum uric acid( UA),24 h urinary protein excretion( 24 h U-pro),urinary IL-18 and Kim-1 were detected and compared before and after treatment. Additionally,the levels of urinary IL-18 and Kim-1 were compared between the healthy volunteers and the patients with CKD at phase 3. Results: 1Compared with the healthy volunteers,the levels of urinary IL-18 and Kim-1 were obviously increased in patients with CKD( P < 0. 01). 2After treatment,the level of e GFR was increased in the treatment group( P <0. 05),and the levels of Scr and BUN were obviously decreased( P < 0. 05,P < 0. 01); the level of UA was obviously decreased in the control group( P < 0. 05); and the levels of e GFR and UA in the treatment group were higher than those in the control group( P < 0. 05),and the levels of Scr and BUN in the treatment group were lower than those in the control group( P < 0. 05,P < 0. 01). 3After treatment,the levels of 24 h U-pro,urinary IL-18 and Kim-1 were significantly decreased in both groups( P < 0. 05,P < 0. 01),and the level of 24 h U-pro in the control group was lower than that in the treatment group( P < 0. 05),the level of urinary IL-18 in the treatment group were lower than that in the control group( P < 0. 05).Conclusion: 1Urinary IL-18 and Kim-1,as the biomarkers of acute kidney injury( AKI),may contribute to the early detection of kidney injury and the efficacy determination in patients with CKD. 2CHR can effectively protect the renal function of patients with CKD at phase 3 and has good application prospect in clinic.
Objective: To observe the influence of "Chuanhuang Recipe No. 1 "( CHR) on the level of urinary interleukin-18( IL-18) and kidney injury molecule-1( Kim-1) in patients with chronic kidney disease( CKD) at phase 3.Methods: Sixty-six patients with CKD at phase 3 were selected and randomly divided into the CHR group( treatment group)and the losartan potassium group( control group) with 33 cases in each group. Meanwhile,20 healthy volunteers were involved as control. All the patients were treated with the conventional medicine,and the patients in the treatment group were treated with CHR and the patients in the control group were treated with losartan tablet in addition,with a course of 24 weeks. The levels of serum creatinine( Scr),blood urea nitrogen( BUN),estimated glomerular filtration rate( e GFR),serum uric acid( UA),24 h urinary protein excretion( 24 h U-pro),urinary IL-18 and Kim-1 were detected and compared before and after treatment. Additionally,the levels of urinary IL-18 and Kim-1 were compared between the healthy volunteers and the patients with CKD at phase 3. Results: 1Compared with the healthy volunteers,the levels of urinary IL-18 and Kim-1 were obviously increased in patients with CKD( P < 0. 01). 2After treatment,the level of e GFR was increased in the treatment group( P <0. 05),and the levels of Scr and BUN were obviously decreased( P < 0. 05,P < 0. 01); the level of UA was obviously decreased in the control group( P < 0. 05); and the levels of e GFR and UA in the treatment group were higher than those in the control group( P < 0. 05),and the levels of Scr and BUN in the treatment group were lower than those in the control group( P < 0. 05,P < 0. 01). 3After treatment,the levels of 24 h U-pro,urinary IL-18 and Kim-1 were significantly decreased in both groups( P < 0. 05,P < 0. 01),and the level of 24 h U-pro in the control group was lower than that in the treatment group( P < 0. 05),the level of urinary IL-18 in the treatment group were lower than that in the control group( P < 0. 05).Conclusion: 1Urinary IL-18 and Kim-1,as the biomarkers of acute kidney injury( AKI),may contribute to the early detection of kidney injury and the efficacy determination in patients with CKD. 2CHR can effectively protect the renal function of patients with CKD at phase 3 and has good application prospect in clinic.
引文
[1]张路霞,王芳,王莉,等.中国慢性肾脏病患病率的横断面调查[J].世界临床医学,2012,6(3):171-179.
[2]龚学忠,王跃荣,符丹,等.制大黄-川芎药对对造影剂肾病大鼠肾小管上皮细胞凋亡的影响[J].中国中西医结合肾病杂志,2012,13(8):675-677.
[3]龚学忠,王骞,符丹,等.制大黄-川芎“药对”抑制造影剂肾病大鼠肾小管上皮细胞凋亡信号通路的机制研究[J].上海中医药杂志,2013,47(3):69-71.
[4]龚学忠,周令芳,王骞,等.川黄1号方对慢性肾脏病3期患者肾功能及微炎症状态的影响[J].中国中西医结合杂志,2015,35(2):137-141.
[5]Sabbisetti VS,Waikar SS,Antoine DJ,et al.Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes[J].J Am Soc Nephrol,2014,25(10):2177-2186.
[6]Yong K,Ooi EM,Dogra G,et al.Elevated interleukin-12 and interleukin-18 in chronic kidney disease are not associated with arterial stiffness[J].Cytokine,2013,64(1):39-42.
[7]de Vinuesa SG,Goicoechea M,Kanter J,et al.Insulin resistance,inflammatory biomarkers,and adipokines in patients with chronic kidney disease:effects of angiotensinⅡblockade[J].J Am Soc Nephrol,2006,17(12 Suppl 3):S206-S212.
[8]郑筱萸.中药新药临床研究指导原则(试行)[M].北京:中国医药科技出版社,2002:156-161.
[9]中华中医药学会肾病分会.慢性肾衰竭的诊断、辨证分型及疗效评定(试行方案)[J].上海中医药杂志,2006,40(8):8-9.
[10]Leslie JA,Meldrum KK.The role of interleukin-18 in renal injury[J].J Surg Res,2008,145(1):170-175.
[11]Liang D,Liu HF,Yao CW,et al.Effects of interleukin 18 on injury and activation of human proximal tubular epithelial cells[J].Nephrology,2007,12(1):53-61.
[12]Driver TH,Katz R,Ix JH,et al.Urinary kidney injury molecule 1(KIM-1)and interleukin 18(IL-18)as risk markers for heart failure in older adults:the Health,Aging,and Body Composition(Health ABC)Study[J].Am J Kidney Dis,2014,64(1):49-56.
[13]Koyner JL,Garg AX,Coca SG,et al.Biomarkers predict progression of acute kidney injury after cardiac surgery[J].J Am Soc Nephrol,2012,23(5):905-914.
[14]郑平东.慢性肾衰竭病因病机与临证辨治[J].上海中医药大学学报,2008,22(2):1-3.
[15]龚学忠.从“毒瘀互结”论治造影剂肾病[J].上海中医药杂志,2012,46(2):57-59.
[16]王永钧,何立群,孙伟,等.中药辨证组方对慢性肾脏病3期的肾保护作用——315例多中心、前瞻性、双盲、随机对照试验[J].世界中医药,2013,8(9):1001-1006.
[17]高建明,朱强,朱为瑷.黄芪与川芎嗪联合治疗慢性肾小球肾炎蛋白尿[J].江苏大学学报:医学版,2005,15(6):509-510.
[2]龚学忠,王跃荣,符丹,等.制大黄-川芎药对对造影剂肾病大鼠肾小管上皮细胞凋亡的影响[J].中国中西医结合肾病杂志,2012,13(8):675-677.
[3]龚学忠,王骞,符丹,等.制大黄-川芎“药对”抑制造影剂肾病大鼠肾小管上皮细胞凋亡信号通路的机制研究[J].上海中医药杂志,2013,47(3):69-71.
[4]龚学忠,周令芳,王骞,等.川黄1号方对慢性肾脏病3期患者肾功能及微炎症状态的影响[J].中国中西医结合杂志,2015,35(2):137-141.
[5]Sabbisetti VS,Waikar SS,Antoine DJ,et al.Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes[J].J Am Soc Nephrol,2014,25(10):2177-2186.
[6]Yong K,Ooi EM,Dogra G,et al.Elevated interleukin-12 and interleukin-18 in chronic kidney disease are not associated with arterial stiffness[J].Cytokine,2013,64(1):39-42.
[7]de Vinuesa SG,Goicoechea M,Kanter J,et al.Insulin resistance,inflammatory biomarkers,and adipokines in patients with chronic kidney disease:effects of angiotensinⅡblockade[J].J Am Soc Nephrol,2006,17(12 Suppl 3):S206-S212.
[8]郑筱萸.中药新药临床研究指导原则(试行)[M].北京:中国医药科技出版社,2002:156-161.
[9]中华中医药学会肾病分会.慢性肾衰竭的诊断、辨证分型及疗效评定(试行方案)[J].上海中医药杂志,2006,40(8):8-9.
[10]Leslie JA,Meldrum KK.The role of interleukin-18 in renal injury[J].J Surg Res,2008,145(1):170-175.
[11]Liang D,Liu HF,Yao CW,et al.Effects of interleukin 18 on injury and activation of human proximal tubular epithelial cells[J].Nephrology,2007,12(1):53-61.
[12]Driver TH,Katz R,Ix JH,et al.Urinary kidney injury molecule 1(KIM-1)and interleukin 18(IL-18)as risk markers for heart failure in older adults:the Health,Aging,and Body Composition(Health ABC)Study[J].Am J Kidney Dis,2014,64(1):49-56.
[13]Koyner JL,Garg AX,Coca SG,et al.Biomarkers predict progression of acute kidney injury after cardiac surgery[J].J Am Soc Nephrol,2012,23(5):905-914.
[14]郑平东.慢性肾衰竭病因病机与临证辨治[J].上海中医药大学学报,2008,22(2):1-3.
[15]龚学忠.从“毒瘀互结”论治造影剂肾病[J].上海中医药杂志,2012,46(2):57-59.
[16]王永钧,何立群,孙伟,等.中药辨证组方对慢性肾脏病3期的肾保护作用——315例多中心、前瞻性、双盲、随机对照试验[J].世界中医药,2013,8(9):1001-1006.
[17]高建明,朱强,朱为瑷.黄芪与川芎嗪联合治疗慢性肾小球肾炎蛋白尿[J].江苏大学学报:医学版,2005,15(6):509-510.