特利加压素联合白蛋白输注治疗肝肾综合征患者疗效及尿NGAL和KIM-1对疗效的预测价值
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摘要
目的探讨尿中性粒细胞明胶酶相关脂质运载蛋白(uNGAL)和肾损伤因子-1(uKIM-1)对特利加压素联合白蛋白输注治疗肝肾综合征患者疗效的预测价值。方法 2017年5月1日～2018年4月30日就诊于北京佑安医院的肝硬化并发I型HRS患者19例,应用特利加压素联合白蛋白输注治疗,采用ELLSA法测定尿NGAL和KIM-1水平。结果经特利加压素联合白蛋白输注治疗4 d后,应答12例(63.2%),未应答7例(36.8%);两组患者年龄和性别比较,差异无统计学意义(P=0.605和P=0.386),两组自发性细菌性腹膜炎(SBP)和上消化道出血发生率比较,差异无统计学意义(P=0.526和P=0.525),两组血清ALT、AST、TBIL、DBIL、BUN、ALB和血小板计数、血红蛋白、白细胞计数等基线资料比较,差异无统计学意义(P>0.05);应答组患者PTA显著高于非应答组(P=0.006),血肌酐水平显著低于非应答组(P=0.043);应答组患者uNGAL/Cr为21.8(7.8～65.5)μg/g,uKIM-1/Cr水平4.9(2.0～7.7)μg/g,均显著低于非应答组【分别为97.8(27.1～358.2)μg/g(P=0.010)和9.1(5.5～13.6)μg/g,P=0.001】;早期应答组患者90 d生存率为75.0%,非应答组为42.9%,差异无统计学意义(P=0.182);血肌酐与uNGAL/Cr呈正相关(r=0.549,P=0.022),而与uKIM-1/Cr无显著相关(r=0.213,P=0.411)。结论基线血肌酐、PTA和尿NGAL水平可以预测特利加压素联合白蛋白输注治疗的肝硬化并发HRS患者的疗效,值得进一步研究。
Objective To explore the predictive value of urinary neutrophil gelatinase-associated lipocalin(uNGAL) and urine kidney injury factor-1(KIM-1) for response of patients with hepatorenal syndrome(HRS) to terlipressin combined with albumin infusion treatment. Methods 19 consecutive patients with liver cirrhosis complicated by HRS type one were recruited in You'an hospital between May 1,2017 and April 30,2018,and all the patients received terlipressin and albumin infusion treatment. Urine NGAL and KIM-1 were detected by ELISA. Results At the end of four day treatment,12(63.2%) responded and 7(36.8%) did not;the age(P=0.605) and gender(P=0.386),the incidences of spontaneous bacterial peritonitis(P=0.526) and gastrointestinal hemorrhage(P=0.525),and serum ALT,AST,bilirubin,blood urea nitrogen,and platelet cell counts,hemoglobin levels and while blood cell counts between the two groups were not significantly different(P >0.05);the prothrombin time activity(PTA) in responded patients was much higher(P=0.006),and serum Cr level was significantly lower than in patients non-responded(P=0.043);uNGAL/Cr was 21.8(7.8 ～65.5) μg/g and uKIM-1/Cr was 4.9(2.0～7.7) μg/g in responded patients,much lower than 97.8(27.1～358.2) μg/g(P=0.010) and 9.1(5.5～13.6) μg/g(P=0.001) in non-responded patients;the 90 d survival in responded patients was 75.0%,not significantly different as compared to 42.9% in non-responded patients(P=0.182);serum Cr was positively correlated to uNGAL/Cr(r =0.549,P =0.022),while was not significantly correlated to uKIM-1/Cr(r =0.213,P =0.411). Conclusion Baseline blood creatinine,PTA and urine NGAL levels might predict the response of patients with HRS to combination of terlipressin and albumin infusion,which warrants further investigation.
Objective To explore the predictive value of urinary neutrophil gelatinase-associated lipocalin(uNGAL) and urine kidney injury factor-1(KIM-1) for response of patients with hepatorenal syndrome(HRS) to terlipressin combined with albumin infusion treatment. Methods 19 consecutive patients with liver cirrhosis complicated by HRS type one were recruited in You'an hospital between May 1,2017 and April 30,2018,and all the patients received terlipressin and albumin infusion treatment. Urine NGAL and KIM-1 were detected by ELISA. Results At the end of four day treatment,12(63.2%) responded and 7(36.8%) did not;the age(P=0.605) and gender(P=0.386),the incidences of spontaneous bacterial peritonitis(P=0.526) and gastrointestinal hemorrhage(P=0.525),and serum ALT,AST,bilirubin,blood urea nitrogen,and platelet cell counts,hemoglobin levels and while blood cell counts between the two groups were not significantly different(P >0.05);the prothrombin time activity(PTA) in responded patients was much higher(P=0.006),and serum Cr level was significantly lower than in patients non-responded(P=0.043);uNGAL/Cr was 21.8(7.8 ～65.5) μg/g and uKIM-1/Cr was 4.9(2.0～7.7) μg/g in responded patients,much lower than 97.8(27.1～358.2) μg/g(P=0.010) and 9.1(5.5～13.6) μg/g(P=0.001) in non-responded patients;the 90 d survival in responded patients was 75.0%,not significantly different as compared to 42.9% in non-responded patients(P=0.182);serum Cr was positively correlated to uNGAL/Cr(r =0.549,P =0.022),while was not significantly correlated to uKIM-1/Cr(r =0.213,P =0.411). Conclusion Baseline blood creatinine,PTA and urine NGAL levels might predict the response of patients with HRS to combination of terlipressin and albumin infusion,which warrants further investigation.
引文
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[12]Boyer TD,Sanyal AJ,Garcia-Tsao G,et al.Predictors of response to terlipressin plus albumin in hepatorenal syndrome(HRS)type 1:relationship of serum creatinine to hemodynamics.J Hepatol,2011,55(2):315-321.
[13]Gustot T,Fernandez J,Garcia E,et al.Clinical course of acute-on-chronic liver failure syndrome and effects on prognosis.Hepatology,2015,62(1):243-252.
[14]Jalan R,Saliba F,Pavesi M,et al.Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure.J Hepatol,2014,61(5):1038-1047.
[15]Fagundes C,Pepin MN,Guevara M,et al.Urinary neutrophil gelatinase-associated lipocalin as biomarker in the differential diagnosis of impairment of kidney function in cirrhosis.JHepatol,2012,57(2):267-273.
[16]Barreto R,Elia C,Sola E,et al.Urinary neutrophil gelatinase-associated lipocalin predicts kidney outcome and death in patients with cirrhosis and bacterial infections.J Hepatol,2014,61(1):35-42.
[17]Tsigou E,Psallida V,Demponeras C,et al.Role of new biomarkers:functional and structural damage.Crit Care Res Pract,2013,2013:361078.
[18]Kashani K,Cheungpasitporn W,Ronco C.Biomarkers of acute kidney injury:the pathway from discovery to clinical adoption.Clin Chem Lab Med,2017,55(8):1074-1089.
[19]Francoz C,Nadim MK,Durand F.Kidney biomarkers in cirrhosis.J Hepatol,2016,65(4):809-824.
[20]Yap DY,Seto WK,Fung J,et al.Serum and urinary biomarkers that predict hepatorenal syndrome in patients with advanced cirrhosis.Dig Liver Dis,2017,49(2):202-206.
[2]Jaques DA,Spahr L,Berra G,et al.Biomarkers for acute kidney injury in decompensated cirrhosis:a prospective study.Nephrology,2018,25(2):45-51.
[3]李谨革,聂青和.肝衰竭并发肝肾综合征临床诊治进展.实用肝脏病杂志,2014,17(2):198-201.
[4]Wong F,Nadim MK,Kellum JA,et al.Working party proposal for a revised classification system of renal dysfunction in patients with cirrhosis.Gut,2011,60(5):702-709.
[5]Alessandria C,Ozdogan O,Guevara M,et al.MELD score and clinical type predict prognosis in hepatorenal syndrome:relevance to liver transplantation.Hepatology,2005,41(6):1282-1289.
[6]Angeli P,Gines P,Wong F,et al.Diagnosis and management of acute kidney injury in patients with cirrhosis:revised consensus recommendations of the international club of ascites.JHepatol,2015,62(4):968-974.
[7]Piano S,Schmidt HH,Ariza X,et al.Association between grade of acute on chronic liver failure and response to terlipressin and albumin in patients with hepatorenal syndrome.Clin Gastroenterol Hepatol,2018[ahead of print].
[8]Facciorusso A,Chandar AK,Murad MH,et al.Comparative efficacy of pharmacological strategies for management of type 1hepatorenal syndrome:a systematic review and network metaanalysis.Lancet Gastroenterol Hepatol,2017,2(2):94-102.
[9]Gifford FJ,Morling JR,Fallowfield JA.Systematic review with meta-analysis:vasoactive drugs for the treatment of hepatorenal syndrome type 1.Aliment Pharmacol Ther,2017,45(5):593-603.
[10]Mattos AZ,Mattos AA,Ribeiro RA.Terlipressin versus noradrenaline in the treatment of hepatorenal syndrome:systematic review with meta-analysis and full economic evaluation.Eur J Gastroenterol Hepatol,2016,28(3):345-351.
[11]于淙,王鲁文,龚作炯.特利加压素治疗肝肾综合征有效性及安全性的Meta分析.实用肝脏病杂志,2013,16(2):119-121.
[12]Boyer TD,Sanyal AJ,Garcia-Tsao G,et al.Predictors of response to terlipressin plus albumin in hepatorenal syndrome(HRS)type 1:relationship of serum creatinine to hemodynamics.J Hepatol,2011,55(2):315-321.
[13]Gustot T,Fernandez J,Garcia E,et al.Clinical course of acute-on-chronic liver failure syndrome and effects on prognosis.Hepatology,2015,62(1):243-252.
[14]Jalan R,Saliba F,Pavesi M,et al.Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure.J Hepatol,2014,61(5):1038-1047.
[15]Fagundes C,Pepin MN,Guevara M,et al.Urinary neutrophil gelatinase-associated lipocalin as biomarker in the differential diagnosis of impairment of kidney function in cirrhosis.JHepatol,2012,57(2):267-273.
[16]Barreto R,Elia C,Sola E,et al.Urinary neutrophil gelatinase-associated lipocalin predicts kidney outcome and death in patients with cirrhosis and bacterial infections.J Hepatol,2014,61(1):35-42.
[17]Tsigou E,Psallida V,Demponeras C,et al.Role of new biomarkers:functional and structural damage.Crit Care Res Pract,2013,2013:361078.
[18]Kashani K,Cheungpasitporn W,Ronco C.Biomarkers of acute kidney injury:the pathway from discovery to clinical adoption.Clin Chem Lab Med,2017,55(8):1074-1089.
[19]Francoz C,Nadim MK,Durand F.Kidney biomarkers in cirrhosis.J Hepatol,2016,65(4):809-824.
[20]Yap DY,Seto WK,Fung J,et al.Serum and urinary biomarkers that predict hepatorenal syndrome in patients with advanced cirrhosis.Dig Liver Dis,2017,49(2):202-206.