中性粒与淋巴细胞比值与2型糖尿病肾病的相关性
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摘要
目的探讨中性粒细胞与淋巴细胞比值(NLR)与2型糖尿病肾病(DKD)的相关性。方法选取2012年7月～2018年6月于北京潞河医院住院治疗的2型糖尿病患者148例,根据患者8 h尿微量白蛋白排泄率(8°UAER)分为5组:8°UAER<20μg/min、血清肌酐正常30例为DM1组;20μg/min≤8°UAER<200μg/min、血清肌酐正常30例为DM2组;8°UAER≥200μg/min、血清肌酐正常28例为DM3组;8°UAER≥200μg/min、血清肌酐>120μmol/L但尚未透析者29例为DM4组;DM5组为临床诊断DKD行血液透析治疗患者,共31例。选取健康对照者29名为对照组(N组)。空腹静脉采血,检测各组血常规、血糖、血脂、肝肾功,DM1、DM2、DM3、DM4组留取8 h尿,检测8°UAER。结果随着DKD进展,NLR逐渐升高,DM4、DM5组高于N、DM1、DM2、DM3组(P <0.05或P <0.01),DM3组高于N组和DM1组(P <0.05)。Pearson相关分析结果显示NLR与年龄(r=0.317,P <0.001)、病程(r=0.306,P <0.001)、8°UAER(r=0.293,P=0.006)、尿素氮(r=0.404,P <0.001)、全段甲状旁腺激素(iPTH)(r=0.465,P <0.001)呈正相关,与肾小球滤过率(r=-0.438,P <0.001)、白蛋白(r=-0.194,P=0.019)、高密度脂蛋白胆固醇(r=-0.182,P=0.028)呈负相关。多元线性回归方程:YLog NLR=0.29+0.54Log8°UAER+0.004年龄(R2=0.152,P=0.001);ROC曲线显示,以NLR=2.29作为切点,诊断DKD的灵敏度和特异度分别为52.6%、73.3%(ROC曲线下面积是0.661,95%CI:0.544～0.779,P=0.014)。结论 NLR在DKD进展过程中逐渐升高,在临床蛋白尿的2型糖尿病患者中显著升高,与8°UAER呈正相关,但NLR升高晚于8°UAER,提示NLR升高可预测DKD的发生。
Objective To investigate the relationship between neutrophil-to-lymphocyte ratio(NLR) and type 2 diabetic kidney disease(DKD). Methods A total of 148 patients with type 2 diabetes mellitus admitted to Beijing Luhe Hospital from July 2012 to June 2018, and they were divided into 5 groups according to urine albumer excretion rate in 8 h(8°UAER). Thirty patients with 8°UAER<20 μg/min and normal serum creatinine were DM1 group; 30 patients with20 μg/min≤8°UAER<200 μg/min and normal serum creatinine were DM2 group; 28 patients with 8°UAER≥200 μg/min and normal serum creatinine were DM3 group; 29 patients with 8 ° UAER ≥ 200 μg/min and serum creatinine >120 μmol/L, not yet been dialysis were DM4 group; 31 patients diagnosed as DKD and been dialysis were DM5 group.Twenty-nine health control individuals were selected as control group(N group). Blood was collected by fasting vein.Blood routine examination, glucose, lipid, liver and kidney function were examined in each group. Eight-hour urine in DM1, DM2, DM3 and DM4 group were collected and 8°UAER were detected. Results NLR gradually increased in DKD progress and NLR in DM4 and DM5 group were higher than that in N, DM1, DM2, DM3 group(P < 0.05 or P < 0.01),NLR in DM3 group was higher than that in N and DM1 group(P < 0.05). The results of Pearson correlationanalysis showed that NLR was positively correlated with age(r = 0.317, P < 0.001), course of disease(r = 0.306, P <0.001), 8°UAER(r = 0.293, P = 0.006), urea nitrogen(r = 0.404, P < 0.001), total parathyroid hormone(iPTH)(r = 0.465,P < 0.001) and was negatively correlated with glomerular filtration rate(r =-0.438, P < 0.001), albumin(r =-0.194, P =0.019), high-density lipoprotein cholesterol(r =-0.182, P = 0.028). Multiple linear regression equation: YLog NLR =0.29+0.54 Log8°UAER+0.004 age(R2= 0.152, P = 0.001). ROC curve showed NLR=2.29 as the cut point, and the sensitivity and specificity of DKD diagnosis were 52.6% and 73.3%(area under the ROC curve is 0.661, 95%CI: 0.544-0.779, P = 0.014). Conclusion NLR gradually increases during the progression of diabetic nephropathy, and is significantly high in patients with type 2 diabetes mellitus with proteinuria. It is positively correlated with 8°UAER, but the increase of NLR is later than 8°UAER, suggesting that increasing NLR may predict the occurrence of diabetic kidney disease.
Objective To investigate the relationship between neutrophil-to-lymphocyte ratio(NLR) and type 2 diabetic kidney disease(DKD). Methods A total of 148 patients with type 2 diabetes mellitus admitted to Beijing Luhe Hospital from July 2012 to June 2018, and they were divided into 5 groups according to urine albumer excretion rate in 8 h(8°UAER). Thirty patients with 8°UAER<20 μg/min and normal serum creatinine were DM1 group; 30 patients with20 μg/min≤8°UAER<200 μg/min and normal serum creatinine were DM2 group; 28 patients with 8°UAER≥200 μg/min and normal serum creatinine were DM3 group; 29 patients with 8 ° UAER ≥ 200 μg/min and serum creatinine >120 μmol/L, not yet been dialysis were DM4 group; 31 patients diagnosed as DKD and been dialysis were DM5 group.Twenty-nine health control individuals were selected as control group(N group). Blood was collected by fasting vein.Blood routine examination, glucose, lipid, liver and kidney function were examined in each group. Eight-hour urine in DM1, DM2, DM3 and DM4 group were collected and 8°UAER were detected. Results NLR gradually increased in DKD progress and NLR in DM4 and DM5 group were higher than that in N, DM1, DM2, DM3 group(P < 0.05 or P < 0.01),NLR in DM3 group was higher than that in N and DM1 group(P < 0.05). The results of Pearson correlationanalysis showed that NLR was positively correlated with age(r = 0.317, P < 0.001), course of disease(r = 0.306, P <0.001), 8°UAER(r = 0.293, P = 0.006), urea nitrogen(r = 0.404, P < 0.001), total parathyroid hormone(iPTH)(r = 0.465,P < 0.001) and was negatively correlated with glomerular filtration rate(r =-0.438, P < 0.001), albumin(r =-0.194, P =0.019), high-density lipoprotein cholesterol(r =-0.182, P = 0.028). Multiple linear regression equation: YLog NLR =0.29+0.54 Log8°UAER+0.004 age(R2= 0.152, P = 0.001). ROC curve showed NLR=2.29 as the cut point, and the sensitivity and specificity of DKD diagnosis were 52.6% and 73.3%(area under the ROC curve is 0.661, 95%CI: 0.544-0.779, P = 0.014). Conclusion NLR gradually increases during the progression of diabetic nephropathy, and is significantly high in patients with type 2 diabetes mellitus with proteinuria. It is positively correlated with 8°UAER, but the increase of NLR is later than 8°UAER, suggesting that increasing NLR may predict the occurrence of diabetic kidney disease.
引文
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[21]Lorenzo C,Hanley AJ,Haffner SM.Differential white cell count and incident type 2 diabetes:the Insulin Resistance Atherosclerosis Study[J].Diabetologia,2014,57(1):83-92.
[2]Wang L,Gao P,Zhang M,et al.Prevalence and Ethnic Pattern of Diabetes and Prediabetes in China in 2013[J].Jama,2017,317(24):2515-2523.
[3]Nelson RG,Tuttle KR.The new KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and CKD[J].Blood Purif,2007,25(1):112-114.
[4]Donath MY.Targeting inflammation in the treatment of type2 diabetes:time to start[J].Nat Rev Drug Discov,2014,13(6):465-476.
[5]Ahsen A,Ulu MS,Yuksel S,et al.As a new inflammatory marker for familial Mediterranean fever:neutrophil-tolymphocyte ratio[J].Inflammation,2013,36(6):1357-1362.
[6]Imtiaz F,Shafique K,Mirza SS,et al.Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population[J].Int Arch Med,2012,5(1):2.
[7]Alberti KG,Zimmet PZ.Definition,diagnosis and classification of diabetes mellitus and its complications.Part 1:diagnosis and classification of diabetes mellitus provisional report of a WHO consultation[J].Diabet Med,1998,15(7):539-553.
[8]Reidy K,Kang HM,Hostetter T,et al.Molecular mechanisms of diabetic kidney disease[J].J Clin Invest,2014,124(6):2333-2340.
[9]Rabbani N,Thornalley PJ.Advanced glycation end products in the pathogenesis of chronic kidney disease[J].Kidney Int,2018,93(4):803-813.
[10]Alicic RZ,Johnson EJ,Tuttle KR.Inflammatory Mechanisms as New Biomarkers and Therapeutic Targets for Diabetic Kidney Disease[J].Adv Chronic Kidney Dis,2018,25(2):181-191.
[11]Sangoi MB,de Carvalho JA,Tatsch E,et al.Urinary inflammatory cytokines as indicators of kidney damage in type 2 diabetic patients[J].Clin Chim Acta,2016,460:178-183.
[12]Jha JC,Banal C,Chow BS,et al.Diabetes and Kidney Disease:Role of Oxidative Stress[J].Antioxid Redox Signal,2016,25(12):657-684.
[13]Turkmen K.Inflammation,oxidative stress,apoptosis,and autophagy in diabetes mellitus and diabetic kidney disease:the Four Horsemen of the Apocalypse[J].Int Urol Nephrol,2017,49(5):837-844.
[14]Szablewski L,Sulima A.The structural and functional changes of blood cells and molecular components in diabetes mellitus[J].Biol Chem,2017,398(4):411-423.
[15]Liu X,Zhang Q,Wu H,et al.Blood Neutrophil to Lymphocyte Ratio as a Predictor of Hypertension[J].Am JHypertens,2015,28(11):1339-1346.
[16]Mertoglu C,Gunay M.Neutrophil-Lymphocyte ratio and Platelet-Lymphocyte ratio as useful predictive markers of prediabetes and diabetes mellitus[J].Diabetes Metab Syndr,2017,11(Suppl 1):S127-S131.
[17]Verdoia M,Schaffer A,Barbieri L,et al.Impact of diabetes on neutrophil-to-lymphocyte ratio and its relationship to coronary artery disease[J].Diabetes Metab,2015,41(4):304-311.
[18]Afsar B.The relationship between neutrophil lymphocyte ratio with urinary protein and albumin excretion in newly diagnosed patients with type 2 diabetes[J].Am J Med Sci,2014,347(3):217-220.
[19]Huang W,Huang J,Liu Q,et al.Neutrophil-lymphocyte ratio is a reliable predictive marker for early-stage diabetic nephropathy[J].Clin Endocrinol(Oxf),2015,82(2):229-233.
[20]Chung FM,Tsai JC,Chang DM,et al.Peripheral total and differential leukocyte count in diabetic nephropathy:the relationship of plasma leptin to leukocytosis[J].Diabetes Care,2005,28(7):1710-1717.
[21]Lorenzo C,Hanley AJ,Haffner SM.Differential white cell count and incident type 2 diabetes:the Insulin Resistance Atherosclerosis Study[J].Diabetologia,2014,57(1):83-92.