脓毒症AKI患者NGAL、KIM 1、Cys C在CRRT联合活血解毒益气汤治疗后的表达及其预后价值
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摘要
目的:观察连续性肾脏替代疗法(CRRT)联合活血解毒益气汤对脓毒症急性肾损伤(AKI)患者中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾损伤分子1(KIM 1)、胱抑素C(Cys C)的影响,探讨这些指标预测患者预后的价值。方法:选取脓毒症患者120例作为研究对象,其中发生AKI者62例,设为AKI组,未发生AKI者58例,设为非AKI组。AKI组采取CRRT联合活血解毒益气汤治疗,非AKI组采取常规基础治疗。观察两组治疗后急性生理与慢性健康评价Ⅱ(APACHEⅡ)分数、序贯器官衰竭评价(SOFA)分数、脑钠肽(BNP)、氧合指数、ICU滞留时间、平均住院天数等常规指标;观察两组患者进入ICU后0 h、6 h、12 h、24 h、48 h血清肌酐(SCr)、NGAL、KIM 1、Cys C的变化情况;分析两组治疗前后Cys C、NGAL、KIM 1水平与SCr水平、SOFA分数、APACHEⅡ分数的相关性;随访28 d,记录两组预后情况,并分析NGAL、KIM 1、Cys C对患者肾脏功能转归和病死率的预测价值。结果:治疗后两组APACHEⅡ分数、SOFA分数、BNP、氧合指数、ICU滞留时间、平均住院天数比较差异有统计学意义(P<0.05)。AKI组SCr、Cys C在入室12 h升高最显著,KIM 1在入院24 h后升高最显著,NGAL在入室0 h时水平最高,均达到峰值,治疗结束后所有指标水平均下降,与非AKI组治疗结束后比较,差异有统计学意义(P<0.05)。NGAL水平、Cys C水平与APACHEⅡ分数呈正相关性。AKI组治疗后近期死亡18例(29.03%),死亡原因大部分为脏器功能衰竭、严重感染或呼吸衰竭;存活44例,其中肾功能慢慢恢复并脱离透析者21例(47.73%),肾脏丢失者23例(52.27%)。结论:CRRT联合活血解毒益气汤治疗通过降低脓毒症AKI患者Cys C水平,调节KIM 1、NGAL表达保护肾功能;NGAL、KIM 1、Cys C可作为预测患者预后的独立指标,NGAL、Cys C的预测价值较高,KIM 1的预测价值较低。
Objective:To observe the expressions of neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule 1(KIM 1) and cystatin C(Cys C) in patients with sepsis-induced acute kidney injury(AKI) treated by continuous renal replacement therapy(CRRT) combined with Huoxue Jiedu Yiqi Decoction and analyze their prognostic value. Methods:A total of 120 patients with sepsis were divided into AKI group(62 cases with sepsis-induced AKI) and non-AKI group(58 cases without sepsis-induced AKI).The AKI group was treated with CRRT combined with Huoxue Jiedu Yiqi Decoction and the non-AKI group was treated with conventional basic therapy. After treatment,routine parameters of the two groups such as acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score,sequential organ failure assessment(SOFA) score,brain natriuretic peptide(BNP),oxygenation index,ICU retention time,average length of hospital stay and so on were observed. The levels of serum creatinine(SCr),NGAL,KIM 1 and Cys C of the two groups were observed at the 0 th,6 th,12 th,24 th and 48 th hour in ICU. The correlation between levels of Cys C,NGAL,KIM 1 and SCr level,SOFA score,APACHE Ⅱ score of the two groups was analyzed before and after treatment. After treatment,the patients were followed for 28 days to record the prognosis.At the same time,the value of NGAL,KIM 1 and Cys C in predicting kidney function and death rate of the patients were analyzed. Results:After treatment,the differences of APACHE Ⅱ scores,SOFA scores,BNP,oxygenation index,ICU retention time and average length of hospital stay between the two groups were statistically significant(P<0.05). In the AKI group,the levels of SCr,Cys C reached a peak value at the12 th hour in ICU,the level of KIM 1 reached a peak value at the 24 th hour in ICU and the level of NGAL reached a peak value at the 0 th hour in ICU. After treatment,all the above parameters of the AKI group were decreased and the differences of these parameters between the two groups were statistically significant(P<0.05). The NGAL level,Cys C level and APACIIE Ⅱ scores were positively correlated. In the AKI group,18 patients(29.03%) died shortly after the treatment. The major causes of death were organ failure,severe infection or respiratory failure. Among the survived 44 cases,21 cases(47.73%) had renal function recovery and were out of dialysis,but the other 23 cases(52.27%) had kidney loss. Conclusions:CRRT therapy combined with Huoxue Jiedu Yiqi Decoction can protect the renal function of patients with sepsis-induced AKI by reducing the level of Cys C and regulating the expressions of KIM 1 and NGAL.The levels of NGAL,KIM 1 and Cys C can be used as independent prognostic parameters for the patients.The predictive value of NGAL and Cys C is high,but the predictive value of KIM 1 is low.
Objective:To observe the expressions of neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule 1(KIM 1) and cystatin C(Cys C) in patients with sepsis-induced acute kidney injury(AKI) treated by continuous renal replacement therapy(CRRT) combined with Huoxue Jiedu Yiqi Decoction and analyze their prognostic value. Methods:A total of 120 patients with sepsis were divided into AKI group(62 cases with sepsis-induced AKI) and non-AKI group(58 cases without sepsis-induced AKI).The AKI group was treated with CRRT combined with Huoxue Jiedu Yiqi Decoction and the non-AKI group was treated with conventional basic therapy. After treatment,routine parameters of the two groups such as acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score,sequential organ failure assessment(SOFA) score,brain natriuretic peptide(BNP),oxygenation index,ICU retention time,average length of hospital stay and so on were observed. The levels of serum creatinine(SCr),NGAL,KIM 1 and Cys C of the two groups were observed at the 0 th,6 th,12 th,24 th and 48 th hour in ICU. The correlation between levels of Cys C,NGAL,KIM 1 and SCr level,SOFA score,APACHE Ⅱ score of the two groups was analyzed before and after treatment. After treatment,the patients were followed for 28 days to record the prognosis.At the same time,the value of NGAL,KIM 1 and Cys C in predicting kidney function and death rate of the patients were analyzed. Results:After treatment,the differences of APACHE Ⅱ scores,SOFA scores,BNP,oxygenation index,ICU retention time and average length of hospital stay between the two groups were statistically significant(P<0.05). In the AKI group,the levels of SCr,Cys C reached a peak value at the12 th hour in ICU,the level of KIM 1 reached a peak value at the 24 th hour in ICU and the level of NGAL reached a peak value at the 0 th hour in ICU. After treatment,all the above parameters of the AKI group were decreased and the differences of these parameters between the two groups were statistically significant(P<0.05). The NGAL level,Cys C level and APACIIE Ⅱ scores were positively correlated. In the AKI group,18 patients(29.03%) died shortly after the treatment. The major causes of death were organ failure,severe infection or respiratory failure. Among the survived 44 cases,21 cases(47.73%) had renal function recovery and were out of dialysis,but the other 23 cases(52.27%) had kidney loss. Conclusions:CRRT therapy combined with Huoxue Jiedu Yiqi Decoction can protect the renal function of patients with sepsis-induced AKI by reducing the level of Cys C and regulating the expressions of KIM 1 and NGAL.The levels of NGAL,KIM 1 and Cys C can be used as independent prognostic parameters for the patients.The predictive value of NGAL and Cys C is high,but the predictive value of KIM 1 is low.
引文
[1] ALOBAIDI R,BASU R K,GOLDSTEIN S L,et al. Sepsis-associated acute kidney injury[J]. Semin Nephrol,2015,35(1):2-11.
[2] DAI X,ZENG Z,FU C,et al. Diagnostic value of neutrophil gelatinase-associated lipocalin,cystatin C,and soluble triggering receptor expressed on myeloid cells-1 in critically ill patients with sepsis-associated acute kidney injury[J]. Crit Care,2015,19(1):223.
[3]姚咏明,盛志勇,林洪远,等. 2001年国际脓毒症定义会议关于脓毒症诊断的新标准[J].中华危重病急救医学,2006,18(11):645-646
[4]王海燕. KDIGO急性肾损伤临床实践指南[M].北京:人民卫生出版社,2013:33.
[5]中华医学会急诊医学分会危重病专家委员会.脓毒症的定义、诊断标准、中医证候诊断要点及说明(草案)[J].中华急诊医学杂志,2007,16(8):797-798.
[6]姚咏明,黄立锋.《2008国际严重脓毒症和脓毒性休克治疗指南》概要[J].中华危重病急救医学,2008,20(3):135-138.
[7]王怡,王翠,郭默宁,等.急性生理与慢性健康评分Ⅱ与诊断相关组风险分析的相关性[J].中国医刊,2016,51(9):91-94.
[8] REMYASRI N,BHANDARY N M,D’SOUZA A D. Initial sequential organ failure assessment score versus simplified acute physiology score to analyze multiple organ dysfunction in infectious diseases in intensive care unit[J].Indian J of Crit Care Med,2016,20(4):210-215.
[9] PETERS E,MEHTA R L,MURRAY P T,et al. Study protocol for a multicentre randomised controlled trial:Safety,tolerability,efficacy and quality of life of a human recombinant alkaline phosphatase in patients with sepsisassociated acute kidney injury(STOP-AKI)[J]. BMJ Open,2016,6(9):e012371.
[10]池锐彬,古伟光,梁美华,等.血清胱抑素C联合APACHEⅡ评分对重症急性肾损伤患者诊断和预后预测的价值[J].中国中西医结合急救杂志,2016,23(4):404-407.
[11] BANG J Y,KIM S O,KIM S G,et al. Cystatin-C is associated with partial recovery of kidney function and progression to chronic kidney disease in living kidney donors:observational study[J]. Medicine,2017,96(5):e6037.
[12] WANG M, ZHANG L, YUE R, et al. Significance of cystatin C for early diagnosis of contrast-induced nephropathy in patients undergoing coronary angiography[J].Med Sci Monitor,2016(22):2956-2961.
[13] KOKURA K,KUROMI Y,ENDO T,et al. A kidney injury molecule-1(Kim-1)gene reporter in a mouse artificial chromosome:the responsiveness to cisplatin toxicity in immortalized mouse kidney S3 cells[J]. J Gene Med,2016,18(10):273-281.
[14]徐建国,金献冠,李钰.尿肾损伤分子1和中性粒细胞明胶酶相关脂质运载蛋白对脓毒症合并急性肾损伤患者早期连续性肾脏替代治疗的预测价值[J].中华危重症医学杂志(电子版),2016,27(4):250-255.
[15]许建宁,徐玉辉,蓝海兵.尿NGAL、KIM-1、L-FABP水平在脓毒症急性肾损伤早期诊断中的临床意义[J].广东医学,2015,12(21):3365-3367.
[16] PATEL M L,SACHAN R,SHYAN R,et al. Diagnostic accuracy of urinary neutrophil gelatinase-associated lipocalin in patients with septic acute kidney injury[J]. Int J Nephrol Renovasc Dis,2016,9(3):161-169.
[17]李红艳. ROC曲线评价血清胱抑素C对早期肾功能损伤的临床诊断价值[J].中国实验诊断学,2017,21(6):958-960.
[18] GAUER S,URBSCHAT A,GRETZ N,et al. Kidney injury molecule-1 is specifically expressed in cysticallytransformed proximal tubules of the PKD/Mhm(cy/+)rat model of polycystic kidney disease[J]. Int J of Mol Sci,2016,17(6):802.
[19]程悠悠,黄庆,叶宏伟. NGAL和Cys-C对脓毒症相关急性肾损伤的早期诊断学意义[J].华南国防医学杂志,2016,12(8):496-499.
[2] DAI X,ZENG Z,FU C,et al. Diagnostic value of neutrophil gelatinase-associated lipocalin,cystatin C,and soluble triggering receptor expressed on myeloid cells-1 in critically ill patients with sepsis-associated acute kidney injury[J]. Crit Care,2015,19(1):223.
[3]姚咏明,盛志勇,林洪远,等. 2001年国际脓毒症定义会议关于脓毒症诊断的新标准[J].中华危重病急救医学,2006,18(11):645-646
[4]王海燕. KDIGO急性肾损伤临床实践指南[M].北京:人民卫生出版社,2013:33.
[5]中华医学会急诊医学分会危重病专家委员会.脓毒症的定义、诊断标准、中医证候诊断要点及说明(草案)[J].中华急诊医学杂志,2007,16(8):797-798.
[6]姚咏明,黄立锋.《2008国际严重脓毒症和脓毒性休克治疗指南》概要[J].中华危重病急救医学,2008,20(3):135-138.
[7]王怡,王翠,郭默宁,等.急性生理与慢性健康评分Ⅱ与诊断相关组风险分析的相关性[J].中国医刊,2016,51(9):91-94.
[8] REMYASRI N,BHANDARY N M,D’SOUZA A D. Initial sequential organ failure assessment score versus simplified acute physiology score to analyze multiple organ dysfunction in infectious diseases in intensive care unit[J].Indian J of Crit Care Med,2016,20(4):210-215.
[9] PETERS E,MEHTA R L,MURRAY P T,et al. Study protocol for a multicentre randomised controlled trial:Safety,tolerability,efficacy and quality of life of a human recombinant alkaline phosphatase in patients with sepsisassociated acute kidney injury(STOP-AKI)[J]. BMJ Open,2016,6(9):e012371.
[10]池锐彬,古伟光,梁美华,等.血清胱抑素C联合APACHEⅡ评分对重症急性肾损伤患者诊断和预后预测的价值[J].中国中西医结合急救杂志,2016,23(4):404-407.
[11] BANG J Y,KIM S O,KIM S G,et al. Cystatin-C is associated with partial recovery of kidney function and progression to chronic kidney disease in living kidney donors:observational study[J]. Medicine,2017,96(5):e6037.
[12] WANG M, ZHANG L, YUE R, et al. Significance of cystatin C for early diagnosis of contrast-induced nephropathy in patients undergoing coronary angiography[J].Med Sci Monitor,2016(22):2956-2961.
[13] KOKURA K,KUROMI Y,ENDO T,et al. A kidney injury molecule-1(Kim-1)gene reporter in a mouse artificial chromosome:the responsiveness to cisplatin toxicity in immortalized mouse kidney S3 cells[J]. J Gene Med,2016,18(10):273-281.
[14]徐建国,金献冠,李钰.尿肾损伤分子1和中性粒细胞明胶酶相关脂质运载蛋白对脓毒症合并急性肾损伤患者早期连续性肾脏替代治疗的预测价值[J].中华危重症医学杂志(电子版),2016,27(4):250-255.
[15]许建宁,徐玉辉,蓝海兵.尿NGAL、KIM-1、L-FABP水平在脓毒症急性肾损伤早期诊断中的临床意义[J].广东医学,2015,12(21):3365-3367.
[16] PATEL M L,SACHAN R,SHYAN R,et al. Diagnostic accuracy of urinary neutrophil gelatinase-associated lipocalin in patients with septic acute kidney injury[J]. Int J Nephrol Renovasc Dis,2016,9(3):161-169.
[17]李红艳. ROC曲线评价血清胱抑素C对早期肾功能损伤的临床诊断价值[J].中国实验诊断学,2017,21(6):958-960.
[18] GAUER S,URBSCHAT A,GRETZ N,et al. Kidney injury molecule-1 is specifically expressed in cysticallytransformed proximal tubules of the PKD/Mhm(cy/+)rat model of polycystic kidney disease[J]. Int J of Mol Sci,2016,17(6):802.
[19]程悠悠,黄庆,叶宏伟. NGAL和Cys-C对脓毒症相关急性肾损伤的早期诊断学意义[J].华南国防医学杂志,2016,12(8):496-499.