联合检测血清NGAL、KIM-1和SCr可有效提高慢性肾病分期诊断
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摘要
为了探讨中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin, NGAL)和肾损伤分子-1 (kidney injury molecule-1, KIM-1)以及血肌酐(serum creatinine, SCr)联合检测对慢性肾病(chronic kidney disease, CKD)的早期诊断价值,本研究收集260例肾病患者和85例健康体检者,检测其血清NGAL、KIM-1和SCr水平。依据肾功能分级标准,CKD患者分为CKD 1期(53例),CKD 2期(68例),CKD 3期(71例),CKD 4期(46例)和CKD 5期(22例),并分析以上指标在各组间的含量差异,及其联合测定对CKD早期的敏感性。与健康对照组相比较,CKD 1期、CKD 2期、3期、4期和5期患者的NGAL、KIM-1水平均明显升高(p<0.001)。血清SCr含量在CKD 3期、4期和5期组较健康对照组显著增加(p<0.001)。以上3项指标均随着CKD严重程度增加而升高。各组指标阳性率分析显示,3项联合检测阳性率高于单项检测阳性率。ROC曲线分析NGAL、KIM-1、SCr对CKD诊断的AUC值F分别是为0.824、0.805、0.856。相关性分析结果显示,GFR和NGAL、KIM-1、SCr相关系数分别是r=-0.784、-0.756、-0.728 (p<0.05)。NGAL与KIM-1、SCr的相关系数分别是r=0.932、0.764 (p<0.05);KIM-1与SCr的相关系数r分别是0.791 (p<0.05)。本研究初步得出结论:血清NGAL、Kim-1可作为CKD早期诊断的重要指标,联合检测血清NGAL、Kim-1、SCr可有效提高CKD早期肾损伤诊断的敏感度,对CKD的分期诊断和治疗具有极其重要的临床价值。
In order to explored the early diagnostic value of combined detection of serum Neutrophil Gelatinase-Associated Lipocalin(NGAL), Kidney Injury Molecule-1(KIM-1) and serum creatinine(SCr) in the diagnosis of chronic kidney disease(CKD) staging, 260 CKD patients and 85 cases of physical examination from March 2016 to June 2017 were enrolled in this study, the serum NGAL, KIM-1 and serum creatinine(SCr) level of them were measured.Based on the grading standard for renal function, the CKD patients were divided into five stages: CKD stage 1(53samples), CKD stage 2(68 samples), CKD stage 3(71 samples), CKD stage 4(46 samples) and CKD stage 5(22samples). The content differences of NGAL, KIM-1 and SCr, as well as the sensitivity of the combined determination to the early stage of CKD were both analyzed among the groups. Compared with the healthy control group, the contents of NGAL and KIM-1 were obviously elevated at CKD stages 1～5(p<0.001), while the level of SCr was markedly increased at CKD stages 3～5 when compared to the controls(p<0.001). Moreover, the levels of NGAL, KIM-1 and SCr were increased along with the severity of CKD progress. We found that in each CKD stage, the positive rate of the combined detection of three indicators was higher than that of single detection. ROC curves analysis demonstrated that the AUC of NGAL, KIM-1 and SCr in CKD patients were 0.824, 0.805, 0.856, respectively. Correlation analysis demonstrated that GFR and NGAL, KIM-1, SCr were with the coefficient-0.784,-0.756, and-0.728, respectively(p<0.05). NGAL and KIM-1 were with the correlation coefficient 0.932(p<0.05). Our study preliminarily concluded that serum NGAL and Kim-1 could be used as an important index for early diagnosis of CKD, and combined detection of serum NGAL, Kim-1, and SCr could effectively improve the sensitivity of diagnosing the early renal damage of CKD. It might be an important clinical value for staging diagnosis and treatment of CKD.
In order to explored the early diagnostic value of combined detection of serum Neutrophil Gelatinase-Associated Lipocalin(NGAL), Kidney Injury Molecule-1(KIM-1) and serum creatinine(SCr) in the diagnosis of chronic kidney disease(CKD) staging, 260 CKD patients and 85 cases of physical examination from March 2016 to June 2017 were enrolled in this study, the serum NGAL, KIM-1 and serum creatinine(SCr) level of them were measured.Based on the grading standard for renal function, the CKD patients were divided into five stages: CKD stage 1(53samples), CKD stage 2(68 samples), CKD stage 3(71 samples), CKD stage 4(46 samples) and CKD stage 5(22samples). The content differences of NGAL, KIM-1 and SCr, as well as the sensitivity of the combined determination to the early stage of CKD were both analyzed among the groups. Compared with the healthy control group, the contents of NGAL and KIM-1 were obviously elevated at CKD stages 1～5(p<0.001), while the level of SCr was markedly increased at CKD stages 3～5 when compared to the controls(p<0.001). Moreover, the levels of NGAL, KIM-1 and SCr were increased along with the severity of CKD progress. We found that in each CKD stage, the positive rate of the combined detection of three indicators was higher than that of single detection. ROC curves analysis demonstrated that the AUC of NGAL, KIM-1 and SCr in CKD patients were 0.824, 0.805, 0.856, respectively. Correlation analysis demonstrated that GFR and NGAL, KIM-1, SCr were with the coefficient-0.784,-0.756, and-0.728, respectively(p<0.05). NGAL and KIM-1 were with the correlation coefficient 0.932(p<0.05). Our study preliminarily concluded that serum NGAL and Kim-1 could be used as an important index for early diagnosis of CKD, and combined detection of serum NGAL, Kim-1, and SCr could effectively improve the sensitivity of diagnosing the early renal damage of CKD. It might be an important clinical value for staging diagnosis and treatment of CKD.
引文
Ahn J.Y.,Lee M.J.,Seo J.S.,Choi D.,and Park J.B.,2016,Plasma neutrophil gelatinase-associated lipocalin as a predictive biomarker for the detection of acute kidney injury in adult poisoning,Clinical Toxicology(Phila),54(2):127-133
Bolignano D.,Lacquaniti A.,Coppolino G.,Donato V.,Campo S.,Fazio M.R.,Nicocia G.,and Buemi M.,2009,Neutrophil gelatinase-associated lipocalin(NGAL)and progression of chronic kidney disease,Clinical Journal of the American Society of Nephrology Cjasn,4(2):337-344
Bonventre J.V.,and Yang L.,2010,Kidney injury molecule-1,Current Opinion in Critical Care,16(6):556-561
Bonventre J.V.,2009,Kidney injury molecule-1(KIM-1):a urinary biomarker and much more,Nephrol.Dial.Transplant,24(11):3265-3268
Hill N.R.,Fatoba S.T.,Oke J.L.,Hirst J.A.,O'Callaghan C.A.,Lasserson D.S.,and Hobbs F.D.,2016,Global prevalence of chronic kidney diseasea systematic review and meta-analysis,PLoS One,11(7):e0158765
Khatami M.R.,Sabbagh M.R.,Nikravan N.,Khazaeipour Z.,Borouman M.A.,Sadeghian S.,and Davoudi B.,2015,The role of neutrophil-gelatinase-associated lipocalin in early diagnosis of contrast nephropathy,Indian J.Nephrol.,25(5):292-296
Khan Z.,and Pandey M.,2014,Role of kidney biomarkers of chronic kidney disease:An update,Saudi.J.Biol.Sci.,21(4):294-299
Levey A.S.,Stevens L.A.,Schmid C.H.,Zhang Y.L.,Castro A.F.,Feldman H.I.,Kusek J.W.,Eggers P.,Van Lente F.,Greene T.,and Coresh J.,2009,A new equation to esti mate glomerular filtration rate.,Ann.Intern.Med.,150(9):604-612
Moriya H.,Mochida Y.,Ishioka K.,Oka M.,Maesato K.,Hidaka S.,Ohtake T.,and Kobayashi S.,2017,Plasma neutrophil gelatinase-associated lipocalin(NGAL)is an indicator of interstitial damage and a predictor of kidney function worsening of chronic kidney disease in the early stage:a pilot study,Clinical&Experimental Nephrology,10(21):1-7
Rysz J.,Gluba-Brzózka A.,Franczyk B.,Jabonowski Z.,and Ciakowska-Rysz A.,2017,Novel biomarkers in the diagnosis of chronic kidney disease and the prediction of its outcome,Int.J.Mol.Sci.,18(8):E1702
Sabbisetti V.S.,Waikar S.S.,Antoine D.J.,Smiles A.,Wang C.,Ravisankar A.,Ito K.,Sharma S.,Ramadesikan S.,Lee M.,Briskin R.,De Jager P.L.,Ngo T.T.,Radlinski M.,Dear J.W.,Park K.B.,Betensky R.,Krolewski A.S.,and Bonventre J.V.,2014,Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes,J.Am.Soc.Nephrol.,25(10):2177-2186
Wagener G.,Gubitosa G.,Wang S.,Borregaard N.,Kim M.,and Lee H.T.,2008,Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery,Am.J.Kidney Dis.,52(3):425-433
Wasung M.E.,Chawla L.S.,and Madero M.,2015,Biomarkers of renal function,which and when?Clin.Chim.Acta.,438(438):350-357
Zoccali C.,Vanholder R.,Massy Z.A.,Ortiz A.,Sarafidis P.,Dekker F.W.,Fliser D.,Fouque D.,Heine G.H.,Jager K.J.,Kanbay M.,Mallamaci F.,Parati G.,Rossignol P.,Wiecek A.,and London G.,2017,The systemic nature of CKD,Nat.Rev.Nephrol.,13(6):344-358
Bolignano D.,Lacquaniti A.,Coppolino G.,Donato V.,Campo S.,Fazio M.R.,Nicocia G.,and Buemi M.,2009,Neutrophil gelatinase-associated lipocalin(NGAL)and progression of chronic kidney disease,Clinical Journal of the American Society of Nephrology Cjasn,4(2):337-344
Bonventre J.V.,and Yang L.,2010,Kidney injury molecule-1,Current Opinion in Critical Care,16(6):556-561
Bonventre J.V.,2009,Kidney injury molecule-1(KIM-1):a urinary biomarker and much more,Nephrol.Dial.Transplant,24(11):3265-3268
Hill N.R.,Fatoba S.T.,Oke J.L.,Hirst J.A.,O'Callaghan C.A.,Lasserson D.S.,and Hobbs F.D.,2016,Global prevalence of chronic kidney diseasea systematic review and meta-analysis,PLoS One,11(7):e0158765
Khatami M.R.,Sabbagh M.R.,Nikravan N.,Khazaeipour Z.,Borouman M.A.,Sadeghian S.,and Davoudi B.,2015,The role of neutrophil-gelatinase-associated lipocalin in early diagnosis of contrast nephropathy,Indian J.Nephrol.,25(5):292-296
Khan Z.,and Pandey M.,2014,Role of kidney biomarkers of chronic kidney disease:An update,Saudi.J.Biol.Sci.,21(4):294-299
Levey A.S.,Stevens L.A.,Schmid C.H.,Zhang Y.L.,Castro A.F.,Feldman H.I.,Kusek J.W.,Eggers P.,Van Lente F.,Greene T.,and Coresh J.,2009,A new equation to esti mate glomerular filtration rate.,Ann.Intern.Med.,150(9):604-612
Moriya H.,Mochida Y.,Ishioka K.,Oka M.,Maesato K.,Hidaka S.,Ohtake T.,and Kobayashi S.,2017,Plasma neutrophil gelatinase-associated lipocalin(NGAL)is an indicator of interstitial damage and a predictor of kidney function worsening of chronic kidney disease in the early stage:a pilot study,Clinical&Experimental Nephrology,10(21):1-7
Rysz J.,Gluba-Brzózka A.,Franczyk B.,Jabonowski Z.,and Ciakowska-Rysz A.,2017,Novel biomarkers in the diagnosis of chronic kidney disease and the prediction of its outcome,Int.J.Mol.Sci.,18(8):E1702
Sabbisetti V.S.,Waikar S.S.,Antoine D.J.,Smiles A.,Wang C.,Ravisankar A.,Ito K.,Sharma S.,Ramadesikan S.,Lee M.,Briskin R.,De Jager P.L.,Ngo T.T.,Radlinski M.,Dear J.W.,Park K.B.,Betensky R.,Krolewski A.S.,and Bonventre J.V.,2014,Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes,J.Am.Soc.Nephrol.,25(10):2177-2186
Wagener G.,Gubitosa G.,Wang S.,Borregaard N.,Kim M.,and Lee H.T.,2008,Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery,Am.J.Kidney Dis.,52(3):425-433
Wasung M.E.,Chawla L.S.,and Madero M.,2015,Biomarkers of renal function,which and when?Clin.Chim.Acta.,438(438):350-357
Zoccali C.,Vanholder R.,Massy Z.A.,Ortiz A.,Sarafidis P.,Dekker F.W.,Fliser D.,Fouque D.,Heine G.H.,Jager K.J.,Kanbay M.,Mallamaci F.,Parati G.,Rossignol P.,Wiecek A.,and London G.,2017,The systemic nature of CKD,Nat.Rev.Nephrol.,13(6):344-358