尿NGAL对脓毒症急性肾损伤CRRT治疗时机的分析
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摘要
目的探讨尿中性粒细胞明胶酶相关脂质转运蛋白(uNGAL)指导脓毒症急性肾损伤(AKI)患者连续性肾脏替代治疗(CRRT)的时机。方法选取2013年1月-2017年6月山西大医院收治的100例脓毒症患者为研究对象。入选后测量uNGAL作为分组标准,uNGAL≥1310 ng/ml者纳入高uNGAL组(n=60),uNGAL<1310 ng/ml者纳入低uNGAL组(n=40);再将高uNGAL组随机分为早期CRRT组(n=30)与标准治疗组(n=30)。比较高uNGAL组与低uNGAL组一般临床资料及临床结局;观察早期CRRT组与标准治疗组治疗前后不同时点uNGAL、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)等炎性因子的变化及临床结局。结果高uNGAL组28 d病死率、透析依赖比例均高于低uNGAL组,差异具有统计学意义(P<0.05)。高uNGAL组患者未使用机械通气时间、非ICU住院时间均少于低uNGAL组,差异具有统计学意义(P<0.05)。早期CRRT组与标准治疗组28 d病死率比较,差异无统计学意义;治疗后早期CRRT组患者无机械通气天数、非ICU住院日均明显长于标准治疗组,差异有统计学意义(P<0.05);早期CRRT组透析依赖比例低于标准治疗组,肾功能恢复率高于标准治疗组,差异均有统计学意义(P<0.05);早期CRRT组患者治疗后uNGAL呈下降趋势,48 h明显下降,与入组时比较差异有统计学意义(P<0.05);标准治疗组uNGAL治疗前后差异无统计学意义。早期CRRT组IL-6、TNF-α水平治疗24 h后下降,48 h进一步下降,与治疗前比较差异均有统计学意义(P<0.05);标准治疗组治疗后IL-6、TNF-α水平与治疗前比较差异均无统计学意义。治疗后48 h,两组uNGAL、IL-6水平比较,差异均有统计学意义(P<0.05)。结论使用uNGAL对脓毒症AKI患者进行分类可行,可作为指导CRRT启动的指标。
Objective To investigate the effect of urinary neutrophil gelatinase-associated lipocalin(uNGAL) on the timing of continuous renal replacement therapy(CRRT) in patients with acute renal injury(AKI) associated with sepsis.Methods One hundred patients with sepsis admitted to Shanxi Grand Hospital from January 2013 to June 2017 were selected as research objects.Sixty patients with uNGAL greater than 1310 ng/ml were defined as high uNGAL group,and 40 patients with uNGAL smaller than1310 ng/ml were defined as low uNGAL group.The high uNGAL group was randomly assigned to the early CRRT group or standard treatment group.The clinical outcomes were compared between the high uNGAL group and the low uNGAL group.Changes in the levels of uNGAL,TNF-α and IL-6 inflammatory factors at different time points before and after treatment in the early CRRT group and the standard treatment group.Results The 28 d mortality and dialysis dependence rate in the high uNGAL group were significantly higher than those in the low uNGAL group(P<0.05).The patients in the high uNGAL group had less time without mechanical ventilation and less time out of ICU than those in the low uNGAL group(P<0.05).There was no statistically significant difference in mortality between the early CRRT group and the standard treatment group at 28 d.Days without mechanical ventilation and days without ICU stay in the early treatment group were significantly longer than those in the standard treatment group(P<0.05).The ratio of dialysis dependence was lower in the early CRRT group than in the standard treatment group,and the recovery rate of renal function was higher(P<0.05).In the early CRRT group,uNGAL showed a decreasing trend after treatment,which significantly decreased at 48 h(P<0.05).There was no significant difference between the uNGAL levels before and after treatment in the standard treatment group.The levels of IL-6 and TNF-α in the early CRRT group decreased 24 h after treatment,and further decreased 48 h(P<0.05).The levels of IL-6 and TNF-α showed no significant changes after the treatment in standard treatment group,but there were statistically significant changes in the uNGAL and IL-6 levels 48 h after the treatment in the two groups.Conclusion It is feasible to use uNGAL to classify patients with sepsis AKI and uNGALcan be a reliable indicator to guide the initiation of CRRT.
Objective To investigate the effect of urinary neutrophil gelatinase-associated lipocalin(uNGAL) on the timing of continuous renal replacement therapy(CRRT) in patients with acute renal injury(AKI) associated with sepsis.Methods One hundred patients with sepsis admitted to Shanxi Grand Hospital from January 2013 to June 2017 were selected as research objects.Sixty patients with uNGAL greater than 1310 ng/ml were defined as high uNGAL group,and 40 patients with uNGAL smaller than1310 ng/ml were defined as low uNGAL group.The high uNGAL group was randomly assigned to the early CRRT group or standard treatment group.The clinical outcomes were compared between the high uNGAL group and the low uNGAL group.Changes in the levels of uNGAL,TNF-α and IL-6 inflammatory factors at different time points before and after treatment in the early CRRT group and the standard treatment group.Results The 28 d mortality and dialysis dependence rate in the high uNGAL group were significantly higher than those in the low uNGAL group(P<0.05).The patients in the high uNGAL group had less time without mechanical ventilation and less time out of ICU than those in the low uNGAL group(P<0.05).There was no statistically significant difference in mortality between the early CRRT group and the standard treatment group at 28 d.Days without mechanical ventilation and days without ICU stay in the early treatment group were significantly longer than those in the standard treatment group(P<0.05).The ratio of dialysis dependence was lower in the early CRRT group than in the standard treatment group,and the recovery rate of renal function was higher(P<0.05).In the early CRRT group,uNGAL showed a decreasing trend after treatment,which significantly decreased at 48 h(P<0.05).There was no significant difference between the uNGAL levels before and after treatment in the standard treatment group.The levels of IL-6 and TNF-α in the early CRRT group decreased 24 h after treatment,and further decreased 48 h(P<0.05).The levels of IL-6 and TNF-α showed no significant changes after the treatment in standard treatment group,but there were statistically significant changes in the uNGAL and IL-6 levels 48 h after the treatment in the two groups.Conclusion It is feasible to use uNGAL to classify patients with sepsis AKI and uNGALcan be a reliable indicator to guide the initiation of CRRT.
引文
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[13]Liu Y,Davari-Farid S,Arora P,et al.Early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury after cardiac surgery:a systematic review and meta-analysis[J].J Cardiothorac Vasc Anesth,2014,28(3):557-563.
[14]Liu KD,Himmelfarb J,Paganini E,et al.Timing of initiation of dialysis in critically ill patients with acute kidney injury[J].Clin J Am Soc Nephrol,2006,1(5):915-919.
[15]Shiao CC,Wu VC,Li WY,et al.Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery[J].Crit Care,2009,13(5):8171.
[16]Wu VC,Ko WJ,Chang HW,et al.Early renal replacement therapy in patients with postoperative acute liver failure associated with acute renal failure:effect on post-operative outcomes[J].J Am Coll Surg,2007,205(2):266-276.
[17]Murugan R,Wen X, Shah N,et al.Plasma inflammatory and apoptosis markers are associated with dialysis dependence anddeath among critically ill patients receiving renal replacement therapy[J].Nephrol Dial Transpl,2014,29(10):1854-1864.
[18]Kjeldsen L,Johnsen AH,Sengelcv H,et al.Isolation and primary structure of NGAL,a novel protein associated with human neutrophil gelatinase[J].J Biol Chem, 1993,268(14):10425-10432.
[19]Cowland JB, Scrensen OE, Sehested M,et al.Neutrophil gelatinase-associated lipocalin is up-regulated in human epithelial cells by IL-1 beta,but not by TNF-alpha[J].JImmunol,2003,171(12):6630-6639.
[20]Mishra J,Ma Q,Pmda A, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury[J].J Am Soc Ncphrol,2003,14(10):2534-2543.
[21]Chawla LS, Seneff MG, Nelson DR, et al. Elevated plasma concentrations of IL-6 and elevated APACHEⅡscore predict acute kidney injury in patients with severe sepsis[J].Clin J Am Soc Nephrol,2007,2(1):22-30.
[2]Srisawat N, Sileanu FE,Murugan R,et al. Variation in riskand mortality of acute kidney injury in critically ill patients:a multicenter study[J].Am J Nephrol,2015,41(1):81-88.
[3]Jun M,Heerspink HJ,Ninomiya T,et al. Intensities of renal replacement therapy in acute kidney injury:a systematic review and meta-analysis[J].Clin J Am Soc Nephrol,2010,5(6):956-963.
[4]Huang QY,Wei YP,Liao S.Effect of continuous renal replacement therapy on organ function in patients with sepsis complicated with acute renal injury[J].Trauma Crit Care Med,2018,6(5):312-313,315.[黄勤英,韦艳萍,廖帅.连续性肾替代治疗对脓毒血症合并急性肾损伤患者器官功能影响研究[J].创伤与急危重病医学,2018,6(5):312-313,315.]
[5]KDIG O AKIWork Group.KDIGO clinical practice guideline for acute kidney injury[J].Kidney Int Suppl,2012,2:1-138.
[6]Ronco C,Ricci Z,De Backer D,et al. Renal replacement therapy in acute kidney injury:controversy and consensus[J].Crit Care,2015,19:146.
[7]Lu JH,Pei HH.Advances in early diagnostic markers of sepsisrelated renal injury[j].Trauma Crit Care Med,2017,5(2):125-128.[吕俊华,裴红红.脓毒症相关肾损伤早期诊断标志物研究进展[J].创伤与急危重病医学,2017,5(2):125-128.]
[8]De Geus HR,Bakker J,Lesaffre EM,et al. Neutrophil gelatinaseassociated lipocalin at ICU admission predicts for acute kidney injury in adult patients[J].Am J Respir Crit Care Med,2011,183(7):907-914.
[9]Critical Care Medicine Group of Chinese Medical Association.Guideline of severe sepsis/septic shock treatment of China(2014)[J].Chin Crit Care Med,2015,27(6):401-426.[中华医学会重症医学分会.中国严重脓毒症/脓毒性休克治疗指南(2014)[J].中华危重病急救医学,2015,27(6):401-426.]
[10]KDIGO.Clinical practice guideline for acute kidnev injury[J].Kidney Int Suppl,2012,2:8-12.
[11]Karvellas CJ,Farhat MR,Sajjad I,et al. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury:a systematic review and metaanalysis[J].Crit Care,2011,15(1):R72.
[12]Zarbock A,Kellum JA,Schmidt C,et al. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury:the ELAIN randomized clinical trial[J].JAMA,2016,315(20):2190-2199.
[13]Liu Y,Davari-Farid S,Arora P,et al.Early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury after cardiac surgery:a systematic review and meta-analysis[J].J Cardiothorac Vasc Anesth,2014,28(3):557-563.
[14]Liu KD,Himmelfarb J,Paganini E,et al.Timing of initiation of dialysis in critically ill patients with acute kidney injury[J].Clin J Am Soc Nephrol,2006,1(5):915-919.
[15]Shiao CC,Wu VC,Li WY,et al.Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery[J].Crit Care,2009,13(5):8171.
[16]Wu VC,Ko WJ,Chang HW,et al.Early renal replacement therapy in patients with postoperative acute liver failure associated with acute renal failure:effect on post-operative outcomes[J].J Am Coll Surg,2007,205(2):266-276.
[17]Murugan R,Wen X, Shah N,et al.Plasma inflammatory and apoptosis markers are associated with dialysis dependence anddeath among critically ill patients receiving renal replacement therapy[J].Nephrol Dial Transpl,2014,29(10):1854-1864.
[18]Kjeldsen L,Johnsen AH,Sengelcv H,et al.Isolation and primary structure of NGAL,a novel protein associated with human neutrophil gelatinase[J].J Biol Chem, 1993,268(14):10425-10432.
[19]Cowland JB, Scrensen OE, Sehested M,et al.Neutrophil gelatinase-associated lipocalin is up-regulated in human epithelial cells by IL-1 beta,but not by TNF-alpha[J].JImmunol,2003,171(12):6630-6639.
[20]Mishra J,Ma Q,Pmda A, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury[J].J Am Soc Ncphrol,2003,14(10):2534-2543.
[21]Chawla LS, Seneff MG, Nelson DR, et al. Elevated plasma concentrations of IL-6 and elevated APACHEⅡscore predict acute kidney injury in patients with severe sepsis[J].Clin J Am Soc Nephrol,2007,2(1):22-30.