标题：KIM1、TIMP2及炎症指标与2型糖尿病肾病进展风险的相关性研究

      作者：孙小芳 1，尹丽明 2，包利文 1，廖智威 1，付文金 2，王少波 1    广东医科大学厚街临床医学院内分泌科 1、检验科 2，广东 东莞 523960

      卷次： 2024年35卷14期

      【摘要】 目的 检测不同程度肾脏疾病的糖尿病患者中血清肾损伤分子-1 (KIM-1)、金属基质蛋白酶抑制剂-2 (TIMP2)、白介素6 (IL-6)和C反应蛋白(CRP)的水平，并评估其与糖尿病肾脏进展风险的关系。方法 选取2022年3月至2023年3月东莞厚街医院收治的65例2型糖尿病患者纳入研究，根据患者肾脏病变的严重程度，按照改善全球预后指南将糖尿病肾病(DKD)分为低风险组(n=19)、中风险组(n=22)和高风险组(n=24)，同期选择20例体检健康者作为对照组。比较各组受试者血清KIM-1、TIMP-2、IL-6、CRP、糖化血红蛋白(HbAlc)、尿蛋白/肌酐比值(UACR)、低密度脂蛋白胆固醇 (LDL-C)、空腹血糖(FPG)、血清总胆固醇(TC)、肾小球滤过率(eGFR)、高密度脂蛋白胆固醇(HDL-C)、25羟维生素D3 [(25(OH)D3)]和甘油三酯(TG)的水平，采用Pearson法分析血清TIMP-2、KIM-1与DKD糖脂代谢、肾功能指标的相关性，利用受试者工作(ROC)曲线分析血清KIM-1、TIMP-2、IL-6、CRP、KIM-1与TIMP-2联合检测对DKD疾病进展的预测价值。结果 四组受检者血清LDL-C、HDL-C和CRP水平比较差异均无统计学意义(P>0.05)；对照组血清FPG、HbAlc、TIMP2、KIM-1水平分别为(5.13±0.56) mmol/L、(5.56±0.30)%、(4.91±0.76) ng/mL、(0.46±0.33) ng/mL，明显低于低风险组的(12.17±9.82) mmol/L、(9.45±2.46)%、(11.51±25.01) ng/mL、(1.00±0.68) ng/mL及中风险组的(11.35±10.63) mmol/L、(9.73±2.82)%、(30.23±17.42) ng/mL、(1.26±1.31) ng/mL和高风险组的(8.04±7.69) mmol/L、(9.27±2.21)%、(30.51±46.01) ng/mL、(1.63±1.09) ng/mL，而低风险组的血清中TIMP2、KIM-1水平明显低于中风险组、高风险组，差异均有统计学意义(P<0.05)；高风险组患者的血清CREA、IL-6水平分别为(122.00±79.23) μmmol/L、(3.51±5.92) pg/mL，明显高于低风险组的(77.00±42.70) μmmol/L、(0.50±2.79) pg/mL和中风险组的(74.00±32.25) μmmol/L、(1.34±3.61) pg/mL，差异均有统计学意义(P<0.05)；经Spearman相关分析结果显示2型糖尿病肾病患者TIMP-2、KIM-1与HbA1c、IL-6、UACR均呈正相关(P<0.05)，而TIMP-2、KIM-1与 eGFR呈负相关(P<0.05)；经ROC分析结果显示，KIM-1、TIMP-2、IL-6、CRP以及KIM-1联合TIMP-2预测2型糖尿病肾病进展风险的曲线下面积(AUC)分别为0.869、0.867、0.751、0.633和0.935，KIM-1联合TIMP-2预测较各单一指标预测的准确度更高。结论 血清KIM-1、TIMP-2、IL-6、CRP水平升高与2型糖尿病肾病疾病进展密切相关，其中KIM-1联合TIMP-2预测2型糖尿病肾病进展风险的价值较高。
      【关键词】 糖尿病肾病；肾损伤分子-1；金属基质蛋白酶抑制剂-2；炎症因子；相关性
      【中图分类号】 R587.2 【文献标识码】 A 【文章编号】 1003—6350（2024）14—2036—06

Correlation of KIM1, TIMP2, and inflammatory markers with the risk of progression of type 2 diabeticnephropathy.
SUN Xiao-fang 1, YIN Li-ming 2, BAO Li-wen 1, LIAO Zhi-wei 1, FU Wen-jin 2, WANG Shao-bo 1.Department of Endocrinology 1, Department of Clinical Laboratory 2, Houjie Clinical Medical College, Guangdong MedicalUniversity, Dongguan 523960, Guangdong, CHINA
【Abstract】 Objective To measure the levels of blood clear kidney injury molecule-1 (KIM-1), metallomatrixprotease inhibitor-2 (TIMP2), interleukin 6 (IL-6), and C-reactive protein (CRP) in diabetic patients with different de-grees of kidney disease, and to evaluate their relationship with the risk of progression of diabetic kidney disease (DKD).Methods A total of 65 patients with type 2 diabetes who were admitted to Dongguan Houjie Hospital from March2022 to March 2023 were selected for inclusion in the study. Based on the severity of renal lesions, the patients were di-vided into low-risk group (n=19), medium-risk group (n=22), and high-risk group (n=24) according to the Kidney Dis-ease: Improving Global Outcomes (KDIGO), and 20 healthy patients during the same period were selected as the controlgroup. The blood levels of KIM-1, TIMP-2, IL-6, CRP, glycosylated hemoglobin (HbAlc), urine albumin-to-creati-nine ratio (UACR), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FPG), serum total cholesterol(TC), estimated glomerular filtration rate (eGFR), high-density lipoprotein cholesterol (HDL-C), 25-hydroxyvitamin D3[25(OH)D3] and triglycerides (TG) were compared among the four groups. Pearson method was used to analyze the cor-relation of serum TIMP-2, KIM-1 with DKD glucose and lipid metabolism and renal function indexes. Receiver operat-ing curve (ROC) was used to analyze the predictive value of serum KIM-1, TIMP-2, IL-6, CRP, and KIM-1 combinedwith TIMP-2 for DKD progression. Results There were no significant differences in the levels of serum LDL-C,HDL-C, and CRP among the four groups (P>0.05). The serum levels of FPG, HbAlc, TIMP-2, and KIM-1 in the con-trol group were (5.13±0.56) mmol/L, (5.56±0.30)%, (4.91±0.76) ng/mL, and (0.46±0.33) ng/mL, respectively, signifi-cantly lower than (12.17±9.82) mmol/L, (9.45±2.46)%, (11.51±25.01) ng/mL, (1.00±0.68) ng/mL in low-risk groupand (11.35±10.63) mmol/L, (9.73±2.82)%, (30.23±17.42) ng/mL, (1.26±1.31) ng/mL in medium-risk group, and(8.04±7.69) mmol/L, (9.27±2.21)%, (30.51±46.01) ng/mL, (1.63±1.09) ng/mL in high-risk group, respectively; the se-rum levels of TIMP-2 and KIM-1 in the low-risk group were significantly lower than those in the medium-risk groupand the high-risk group; the differences were statistically significant (P<0.05). The serum CREA and IL-6 levelsin the high-risk group were (122.00±79.23) μmol/L and (3.51±5.92) pg/mL, respectively, significantly higherthan (77.00±42.70) μmol/L and (0.50±2.79) pg/mL in the low-risk group and (74.00±32.25) μmol/L, (1.34±3.61) pg/mL in themedium-risk group (P<0.05). Spearman correlation analysis showed that TIMP-2 and KIM-1 were positively correlatedwith HbA1c, IL-6, and UACR in patients with type 2 diabetic nephropathy (P<0.05), while TIMP-2 and KIM-1 werenegatively correlated with eGFR (P<0.05). The area under the curve (AUC) were 0.869, 0.867, 0.751, 0.633, and 0.935,respectively, and the prediction accuracy of KIM-1 combined with TIMP-2 was higher than that of each indicator alone.Conclusion Elevated serum levels of KIM-1, TIMP-2, IL-6, and CRP were closely related to the progression of type2 diabetic nephropathy, and KIM-1 combined with TIMP-2 had a high value in predicting the risk of progression of type2 diabetic nephropathy.
      【Key words】 Diabetic nephropathy; Kidney injury molecule-1; Metallomatrix protease inhibitor-2; Inflammato-ry factors; Correlation