Citation: | GU Shuaishuai, ZHU Lin, JIN Yansheng, DING Lan, FAN Maoxiao. Levels and clinical significance of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 in patients with diabetic nephropathy[J]. Journal of Clinical Medicine in Practice, 2022, 26(13): 35-40. DOI: 10.7619/jcmp.20214347 |
To explore the levels and clinical significance of urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) in patients with diabetic nephropathy (DN).
A total of 254 DN patients were selected as study group, 230 patients with simple type 2 diabetes in the same period were selected as control group, and the clinical materials were compared between the two groups. According to the estimate glomerular filtration rate (eGFR), DN patients were divided into stage I group (n=32), stage Ⅱ group (n=84), stage Ⅲ group (n=90) and stage Ⅳ group (n=48); according to serum creatinine level and urinary volume, the DN patients were divided into AKI group (n=19) and non-AKI group (n=235); the differences in levels of serum creatinine, urinary TIMP-2 and IGFBP7 in different groups were compared. The levels of urinary TIMP-2, IGFBP7 and urinary creatinine were detected by enzyme-linked immunosorbent assay; Pearson test was used to analyze the relationships of urinary TIMP-2 and IGFBP7 with related indicators; receiver operating characteristic (ROC) curve was used to evaluate the efficiency of urinary TIMP-2, IGFBP7 and serum creatinine in diagnosing AKI in DN patients.
The levels of serum creatinine, glycosylated hemoglobin (HbA1c), blood uric acid, urea nitrogen, urinary microalbumin, 24-hour urinary protein quantitation and urinary β2-microglobulin in the study group were significantly higher than those in the control group, while the levels of serum albumin and eGFR were significantly lower than those in the control group (P < 0.05). The levels of serum creatinine, urinary TIMP-2 to urinary creatinine ratio (TIMP-2/urinary creatinine) and urinary IGFBP7 to urinary creatinine ratio (IGFBP7/urinary creatinine) in DN patients in stage Ⅲ and Ⅳ were significantly higher than those in patients in stage Ⅰand Ⅱ(P < 0.05); compared with the non-AKI group, the levels of serum creatinine, urinary TIMP-2/urinary creatinine and urinary IGFBP7/urinary creatinine were significantly higher in the AKI group (P < 0.05). Urinary TIMP-2 and IGFBP7 were positively correlated with serum creatinine, HbA1c, blood uric acid, urea nitrogen, urinary microalbumin, 24-h urinary protein quantitation and urinary β2-microglobulin (P < 0.05), but were negatively correlated with serum albumin and eGFR (P < 0.05). ROC curve showed that the areas under the curve (AUC) of urinary TIMP-2, IGFBP7 and serum creatinine in predicting incidence of AKI in DN patients were 0.676 (95%CI, 0.587 to 0.756), 0.864 (95%CI, 0.792 to 0.918), 0.618 (95%CI, 0.528 to 0.703) respectively, and the AUC of urinary TIMP-2 combined with IGFBP7 in predicting incidence of AKI in DN patients was 0.926 (95%CI, 0.866 to 0.965).
The levels of urinary TIMP-2 and IGFBP7 in DN patients increase with the aggravation of the disease, which have a certain predictive value for AKI in DN patients.
[1] |
PETERS V, YARD B, SCHMITT C P. Carnosine and diabetic nephropathy[J]. Curr Med Chem, 2020, 27(11): 1801-1812. doi: 10.2174/0929867326666190326111851
|
[2] |
FAN Y, YI Z Z, D′AGATI V D, et al. Comparison of kidney transcriptomic profiles of early and advanced diabetic nephropathy reveals potential new mechanisms for disease progression[J]. Diabetes, 2019, 68(12): 2301-2314. doi: 10.2337/db19-0204
|
[3] |
丁士新. 糖尿病肾病住院患者并发急性肾损伤的危险因素分析[J]. 广西医学, 2019, 41(22): 2871-2874. https://www.cnki.com.cn/Article/CJFDTOTAL-GYYX201922016.htm
|
[4] |
KARÁSEK D, VAVERKOVÁH. Diabetic dyslipidemia and microvascular complications of diabetes[J]. Vnitr Lek, 2018, 64(1): 17-24. doi: 10.36290/vnl.2018.003
|
[5] |
ZHAO X Y, CHEN X M, ZHANG Y Y, et al. Kidney injury molecule-1 is upregulated in renal lipotoxicity and mediates palmitate-induced tubular cell injury and inflammatory response[J]. Int J Mol Sci, 2019, 20(14): 3406. doi: 10.3390/ijms20143406
|
[6] |
ASHRAFI JIGHEH Z, GHORBANI HAGHJO A, ARGANI H, et al. Empagliflozin attenuates renal and urinary markers of tubular epithelial cell injury in streptozotocin-induced diabetic rats[J]. Indian J Clin Biochem, 2020, 35(1): 109-114. doi: 10.1007/s12291-018-0790-6
|
[7] |
韩焕钦, 欧进军, 冯冰, 等. 尿IGFBP7及TIMP-2在失代偿期乙型肝炎肝硬化急性肾损伤中的应用价值[J]. 中华肝脏病杂志, 2020, 28(9): 760-765. doi: 10.3760/cma.j.cn501113-20190215-00048
|
[8] |
张卉, 杨晓. 尿[TIMP-2]×[IGFBP-7]对心脏术后患者急性肾损伤早期预测价值的Meta分析[J]. 临床肾脏病杂志, 2019, 19(5): 340-346. doi: 10.3969/j.issn.1671-2390.2019.05.008
|
[9] |
关毅鸣, 王丽妍, 刘文虎. 线粒体功能及其与急性肾损伤和糖尿病肾病的关系[J]. 医学研究杂志, 2020, 49(7): 5-8. https://www.cnki.com.cn/Article/CJFDTOTAL-YXYZ202007003.htm
|
[10] |
徐刚. 尿蛋白与尿肌酐的比值、β2微球蛋白及视黄醇结合蛋白联合检测对糖尿病肾病的早期诊断价值[J]. 实用临床医药杂志, 2020, 24(21): 86-89. doi: 10.7619/jcmp.202021025
|
[11] |
ADLER C, HELLER T, SCHREGEL F, et al. TIMP-2/IGFBP7 predicts acute kidney injury in out-of-hospital cardiac arrest survivors[J]. Crit Care, 2018, 22(1): 126. doi: 10.1186/s13054-018-2042-9
|
[12] |
JOHNSON A C M, ZAGER R A. Mechanisms underlying increased TIMP2 and IGFBP7 urinary excretion in experimental AKI[J]. J Am Soc Nephrol, 2018, 29(8): 2157-2167. doi: 10.1681/ASN.2018030265
|
[13] |
WANG X Y, ROJAS-QUINTERO J, WILDER J, et al. Tissue inhibitor of metalloproteinase-1 promotes polymorphonuclear neutrophil (PMN) pericellular proteolysis by anchoring matrix metalloproteinase-8 and-9 to PMN surfaces[J]. J Immunol, 2019, 202(11): 3267-3281. doi: 10.4049/jimmunol.1801466
|
[14] |
LIU B C, TANG T T, LV L L. How tubular epithelial cell injury contributes to renal fibrosis[J]. Adv Exp Med Biol, 2019, 1165: 233-252.
|
[15] |
ROMAGNOLI S, RICCI Z, RONCO C. Perioperative acute kidney injury: prevention, early recognition, and supportive measures[J]. Nephron, 2018, 140(2): 105-110. doi: 10.1159/000490500
|
[16] |
XIE Y, ANKAWI G, YANG B, et al. Tissue inhibitor metalloproteinase-2 (TIMP-2)·IGF-binding protein-7 (IGFBP7) levels are associated with adverse outcomes in patients in the intensive care unit with acute kidney injury[J]. Kidney Int, 2019, 95(6): 1486-1493. doi: 10.1016/j.kint.2019.01.020
|
[17] |
JOLIAT G R, LABGAA I, DEMARTINES N, et al. Acute kidney injury after liver surgery: does postoperative urine output correlate with postoperative serum creatinine[J]. HPB (Oxford), 2020, 22(1): 144-150. doi: 10.1016/j.hpb.2019.06.016
|
[18] |
FRIED L. When increase in serum creatinine doesn′t imply kidney damage[J]. Clin J Am Soc Nephrol, 2020, 15(3): 304-305. doi: 10.2215/CJN.14521119
|
[19] |
BULLEN A L, KATZ R, LEE A K, et al. The SPRINT trial suggests that markers of tubule cell function in the urine associate with risk of subsequent acute kidney injury while injury markers elevate after the injury[J]. Kidney Int, 2019, 96(2): 470-479. doi: 10.1016/j.kint.2019.03.024
|
[20] |
ZHANG B, SHI Y Q, ZOU J J, et al. High glucose stimulates cell proliferation and Collagen IV production in rat mesangial cells through inhibiting AMPK-K ATP signaling[J]. Int Urol Nephrol, 2017, 49(11): 2079-2086. doi: 10.1007/s11255-017-1654-3
|
[21] |
CAI X J, WANG L, WANG X L, et al. Silence of IGFBP7 suppresses apoptosis and epithelial mesenchymal transformation of high glucose induced-podocytes[J]. Exp Ther Med, 2018, 16(2): 1095-1102.
|