Predictive value of urinary TIMP-2×IGFBP7 for sepsis acute kidney injury: a Meta-analysis

doi:10.3877/cma.j.issn.2096-1537.2022.03.010

Abstract

Abstract:

Objective

To investigate the predictive value of urinary TIMP-2×IGFBP7 for sepsis acute kidney injury (AKI) by the Meta-analysis.

Methods

The database of PubMed, Web of Science, Cochrane, Embase, CNKI, WanFang, VIP and CBM were searched. Data was analyzed by RevMan 5.3 and Meta-Disc 1.4.

Results

Six studies involving 592 patients were included. Among them, 2 studies were from Western countries, while 4 studies were from China. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio with corresponding 95% confidence interval were 0.82 (0.76-0.87), 0.59 (0.54-0.64), 3.11 (1.47-6.56), 0.27 (0.13-0.57) and 12.92 (4.23-39.41), respectively. The area under the curve for summary receiver operating characteristic curves was 0.8497 with a Q* value of 0.7809. Subgroup analysis showed that the predictive accuracy of TIMP-2×IGFBP7 was higher in stage 1 AKI and Chinese population, with AUCs of 0.9072 and 0.8920, respectively.

Conclusion

Urinary TIMP-2×IGFBP7 is an early predictive marker for sepsis AKI, especially in stage 1 AKI and Chinese population.

Key words: Tissue inhibitor of metalloproteinase-2, Insulin-like growth factor binding protein 7, Sepsis, Acute kidney injury

Xiaohong Xiang, Yanjun Zhong, Jinxiu. Li. Predictive value of urinary TIMP-2×IGFBP7 for sepsis acute kidney injury: a Meta-analysis[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2022, 08(03): 240-247.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://icu.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2096-1537.2022.03.010

https://icu.cma-cmc.com.cn/EN/Y2022/V08/I03/240

Figures/Tables 7

References 42

1	Bauer M, Gerlach H, Vogelmann T, et al. Mortality in Sepsis and septic shock in Europe, North America and Australia between 2009 and 2019—results from a systematic review and meta-analysis [J]. Crit Care, 2020, 24(1): 239-247.
2	Xie J, Wang H, Kang Y, et al. The epidemiology of sepsis in Chinese ICUs: a national cross-sectional survey [J]. Crit Care Med, 2020, 48(3): e209-e218.
3	Bagshaw SM, George C, Bellomo R. Early acute kidney injury and Sepsis : a multicentre evaluation [J]. Crit Care, 2008, 12(2): R47-55.
4	Peerapornratana S, Manrique-Caballero CL, Gómez H, et al. Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment [J]. Kidney Int, 2019, 96(5): 1083-1099.
5	Endre ZH, Pickering JW. Acute kidney injury: cell cycle arrest biomarkers win race for AKI diagnosis [J]. Nat Rev Nephrol, 2014, 10(12): 683-685.
6	Kashani K, Al-Khafaji A, Ardiles T, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury [J]. Crit Care, 2013, 17(1): R25-36.
7	Akiel M, Rajasekaran D, Gredler R, et al. Emerging role of insulin-like growth factor-binding protein 7 in hepatocellular carcinoma [J]. J Hepatocell Carcinoma, 2014, 1: 9-19.
8	Degeorges A, Wang F, Frierson HF, et al. Distribution of IGFBP-rP1 in normal human tissues [J]. J Histochem Cytochem, 2000, 48(6): 747-754.
9	Jia HM, Huang LF, Zheng Y, et al. Diagnostic value of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 for acute kidney injury: a meta-analysis [J]. Crit Care, 2017, 21(1): 77-87.
10	王珍珍, 郭腾飞, 吴婷婷, 等. 尿液TIMP-2×IGFBP-7对急性肾损伤的早期诊断价值: meta分析 [J]. 检验医学与临床, 2020, 17(15): 2122-2125, 2129.
11	Su LJ, Li YM, Kellum JA, et al. Predictive value of cell cycle arrest biomarkers for cardiac surgery-associated acute kidney injury: a meta-analysis [J]. Br J Anaesth, 2018, 121(2): 350-357.
12	Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement [J]. Int J Surg, 2010, 8(5): 336-341.
13	Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference [J]. Crit Care Med, 2003, 31(4): 1250-1256.
14	Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) [J]. JAMA, 2016, 315(8): 801-810.
15	中华医学会重症医学分会. 中国严重脓毒症/脓毒性休克治疗指南(2014) [J] .中华内科杂志, 2015, 54(6): 557-581.
16	中华医学会重症医学分会. 成人严重感染与感染性休克血流动力学监测与支持指南 [J]. 中华内科杂志, 2007, 46(4): 344-349.
17	Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury [J]. Kidney Int Suppl, 2012, 2(1): 1-138.
18	Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury [J]. Crit Care, 2007, 11(2): R31-38.
19	Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure-definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group [J]. Crit Care, 2004, 8(4): R204-R212.
20	Zamora J, Abraira V, Muriel A, et al. Meta-DiSc: a software for meta-analysis of test accuracy data [J]. BMC Med Res Methodol, 2006, 6: 31-42.
21	Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses [J]. BMJ, 2003, 327(7414): 557-560.
22	Cuartero M, Ballus J, Sabater J, et al. Cell-cycle arrest biomarkers in urine to predict acute kidney injury in septic and non-septic critically ill patients [J]. Ann Intensive Care, 2017, 7(1): 92-99.
23	Honore PM, Nguyen HB, Gong M, et al. Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 for risk stratification of acute kidney injury in patients with Sepsis [J]. Crit Care Med, 2016, 44(10): 1851-1860.
24	Gonzalez N, Voils S, Shoulders B. Utility of nephrocheck® in predicting acute kidney injury (AKI) among Sepsis patients with vancomycin and beta-lactam exposure [J]. J Am Coll Clin Pharm, 2020, 3(1): 175-176.
25	杨倩, 曹伟, 吕迪宇, 等. 尿基质金属蛋白酶组织抑制剂-2和胰岛素样生长因子结合蛋白-7在脓毒症致AKI中的早期诊断价值 [J]. 中华急诊医学杂志, 2020, 29(9): 1167-1172.
26	唐凯宏, 金英玉. 尿金属蛋白酶组织抑制剂-2·胰岛素样生长因子结合蛋白-7对脓毒血症患者急性肾损伤和肾替代治疗的早期预测价值 [J]. 国际检验医学杂志, 2021, 42(4): 476-480.
27	肖强. NGAL、[TIMP-2]×[IGFBP-7]和sTM联合检测对脓毒症急性肾损伤早期预测价值的研究 [D]. 太原: 山西医科大学, 2021.
28	金魁, 高志凌, 罗会锁, 等. 新型肾损伤标志物TIMP-2*IGFBP-7对急诊危重患者急性肾损伤的预测价值 [J]. 中国急救医学, 2021, 41(8): 669-675.
29	邬兰, 张永, 曾宪涛. QUADAS-2在诊断准确性研究的质量评价工具中的应用 [J]. 湖北医药学院学报, 2013, 32(3): 201-208.
30	Bellomo R, Kellum JA, Ronco C, et al. Acute kidney injury in Sepsis [J]. Intensive Care Med, 2017, 43(6): 816-828.
31	Zhang Z, Lu B, Sheng X, et al. Cystatin C in prediction of acute kidney injury: a systemic review and meta-analysis [J]. Am J Kidney Dis, 2011, 58(3): 356-365.
32	Albert C, Zapf A, Haase M, et al. Neutrophil gelatinase-associated lipocalin measured on clinical laboratory platforms for the prediction of acute kidney injury and the associated need for dialysis therapy: a systematic review and meta-analysis [J]. Am J Kidney Dis, 2020, 76(6): 826-841.
33	Geng J, Qiu Y, Qin Z, et al. The value of kidney injury molecule 1 in predicting acute kidney injury in adult patients: a systematic review and Bayesian meta-analysis [J]. J Transl Med, 2021, 19(1): 105-117.
34	Bihorac A, Chawla LS, Shaw AD, et al. Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication [J]. Am J Respir Crit Care Med, 2014, 189(8): 932-939.
35	Hoste EA, Mccullough PA, Kashani K, et al. Derivation and validation of cutoffs for clinical use of cell cycle arrest biomarkers [J]. Nephrol Dial Transplant, 2014, 29(11): 2054-2061.
36	许心怡, 潘纯, 杨毅. 金属蛋白酶组织抑制剂-2联合胰岛素样生长因子结合蛋白-7对于急性肾损伤早期诊断及预后评估的临床意义 [J/OL]. 中华重症医学电子杂志, 2018, 4(3): 281-284.
37	Johnson ACM, Zager RA. Mechanisms underlying increased TIMP2 and IGFBP7 urinary excretion in experimental AKI [J]. J Am Soc Nephrol, 2018, 29(8): 2157-2167.
38	Bell M, Larsson A, Venge P, et al. Assessment of cell-cycle arrest biomarkers to predict early and delayed acute kidney injury [J]. Dis Markers, 2015, 2015: 1-9.
39	张宇慧, 杨莉. 脓毒症相关急性肾损伤 [J]. 临床内科杂志, 2022, 39(6): 372-376.
40	Li YM, Zhang J, Su LJ, et al. Downregulation of TIMP2 attenuates Sepsis -induced AKI through the NF-κb pathway [J]. Biochim Biophys Acta Mol Basis Dis, 2019, 1865(3): 558-569.
41	Jiang N, Huang R, Zhang J, et al. TIMP2 mediates endoplasmic reticulum stress contributing to Sepsis -induced acute kidney injury [J]. FASEB J, 2022, 36(4): e22228.
42	Yu JT, Hu XW, Yang Q, et al. Insulin-like growth factor binding protein 7 promotes acute kidney injury by alleviating poly ADP ribose polymerase 1 degradation [J]. Kidney Int, 2022: S0085-2538(22)00463-X.

研究文献作者及年份	国家或区域	研究设计	脓毒症诊断	AKI诊断	样本总量（例）	终点事件	达终点事件人数（例）	未达终点事件人数（例）	采样时间
Honore等^［23］，2016	欧洲，北美	PC	Sepsis 2.0	KDIGO	232	AKI 2/3	40	192	入住ICU
Gonzalez等^［24］，2020	美国	RC	未知	未知	51	AKI	31	20	未知
杨倩等^［25］，2020	中国	PC	Sepsis 3.0	KDIGO	85	AKI	37	48	诊断脓毒症12 h
唐凯宏等^［26］，2021	中国	PC	Sepsis 3.0	KDIGO	121	AKI	45	76	入住ICU
肖强^［27］，2021	中国	PC	Sepsis 3.0	KDIGO	40	AKI	10	30	确诊脓毒症0 h
金魁等^［28］，2021	中国	PC	Sepsis 3.0	KDIGO	63	AKI 2/3	30	33	入住ICU

研究文献作者及年份	国家或区域	研究设计	脓毒症诊断	AKI诊断	样本总量（例）	终点事件	达终点事件人数（例）	未达终点事件人数（例）	采样时间
Honore等^［23］，2016	欧洲，北美	PC	Sepsis 2.0	KDIGO	232	AKI 2/3	40	192	入住ICU
Gonzalez等^［24］，2020	美国	RC	未知	未知	51	AKI	31	20	未知
杨倩等^［25］，2020	中国	PC	Sepsis 3.0	KDIGO	85	AKI	37	48	诊断脓毒症12 h
唐凯宏等^［26］，2021	中国	PC	Sepsis 3.0	KDIGO	121	AKI	45	76	入住ICU
肖强^［27］，2021	中国	PC	Sepsis 3.0	KDIGO	40	AKI	10	30	确诊脓毒症0 h
金魁等^［28］，2021	中国	PC	Sepsis 3.0	KDIGO	63	AKI 2/3	30	33	入住ICU

研究文献作者及年份	检测方法	AUC	截断值	敏感度	特异度	真阳（例）	假阳（例）	假阴（例）	真阴（例）
Honore等^［23］，2016	NephroCheck	0.840	0.300	0.950	0.375	38	120	2	72
Gonzalez等^［24］，2020	NephroCheck	未知	0.300	0.581	0.700	18	6	13	14
杨倩等^［25］，2020	ELISA，上海	1.000	2.090	0.973	0.917	36	4	1	44
唐凯宏等^［26］，2021	ELISA，上海	0.877	0.825	0.844	0.803	38	15	7	61
肖强等^［27］，2021	ELISA，北京	0.834	0.380	0.600	0.900	6	3	4	27
金魁等^［28］，2021	NephroCheck	0.630	0.300	0.767	0.515	23	16	7	17

研究文献作者及年份	检测方法	AUC	截断值	敏感度	特异度	真阳（例）	假阳（例）	假阴（例）	真阴（例）
Honore等^［23］，2016	NephroCheck	0.840	0.300	0.950	0.375	38	120	2	72
Gonzalez等^［24］，2020	NephroCheck	未知	0.300	0.581	0.700	18	6	13	14
杨倩等^［25］，2020	ELISA，上海	1.000	2.090	0.973	0.917	36	4	1	44
唐凯宏等^［26］，2021	ELISA，上海	0.877	0.825	0.844	0.803	38	15	7	61
肖强等^［27］，2021	ELISA，北京	0.834	0.380	0.600	0.900	6	3	4	27
金魁等^［28］，2021	NephroCheck	0.630	0.300	0.767	0.515	23	16	7	17

研究类型（纳入的研究数目）	敏感度（95%CI）	特异度（95%CI）	阳性似然比（95%CI）	阴性似然比（95%CI）	诊断比值比（95%CI）	AUC
总体（6）	0.82（0.76~0.87）	0.59（0.54~0.64）	3.11（1.47~6.56）	0.27（0.13~0.57）	12.92（4.23~39.41）	0.8497
I²（%）	81.8	94.7	93.5	79.3	75.5
P值	0	0	0	0.0002	0.0011
AKI分期
AKI 2/3期（2）	0.87（0.77~0.94）	0.40（0.33~0.46）	1.53（1.35~1.73）	0.27（0.07~1.06）	5.75（1.73~19.14）	-
I²（%）	80.9	55.9	0	68.4	44.5
P值	0.0221	0.1321	0.8308	0.0753	0.1795
AKI 1期（4）	0.80（0.71~0.86）	0.84（0.78~0.89）	4.61（2.29~9.31）	0.25（0.09~0.73）	20.68（4.06~105.28）	0.9072
I²（%）	85.4	54.2	68.8	86.0	80.5
P值	0.0001	0.0875	0.022	0.0001	0.0015
检测方法
NephroCheck（3）	0.78（0.69~0.86）	0.42（0.36~0.48）	1.54（1.36~1.74）	0.39（0.17~0.89）	4.54（2.13~9.67）	0.6842
I²（%）	86.9	78.3	0	68.7	12.6
P值	0.0005	0.0100	0.7223	0.0411	0.3183
ELISA（3）	0.87（0.78~0.93）	0.86（0.79~0.91）	6.14（3.14~1.99）	0.18（0.05~0.62）	40.08（7.53~213.33）	0.9356
I²（%）	79.4	47.0	49.3	79.4	69.2
P值	0.0079	0.5170	0.1389	0.0077	0.0391
采样时间
ICU/未知（4）	0.80（0.73~0.86）	0.51（0.45~0.57）	2.08（1.17~3.7）	0.32（0.15~0.68）	7.35（2.72~19.89）	0.7759
I²（%）	81.3	93.4	89.0	75.4	65.8
P值	0.0011	0	0	0.0068	0.0324
脓毒症（2）	0.89（0.77~0.96）	0.91（0.82~0.96）	9.03（4.32~18.9）	0.12（0~4.15）	67.94（2.35~1964.30）	-
I²（%）	89.1	0	0	91.2	82.3
P值	0.0024	0.8033	0.3677	0.0007	0.0174
地区
欧美（2）	0.79（0.68~0.88）	0.41（0.34~0.48）	1.53（1.35~1.74）	0.31（0.04~2.18）	5.69（1.57~20.65）	-
I²（%）	93.4	87.2	0	86.5	47.4
P值	0.0001	0.0051	0.4190	0.0065	0.1679
亚洲（4）	0.84（0.77~0.90）	0.80（0.73~0.85）	4.34（1.72~11.00）	0.24（0.10~0.60）	20.80（4.17~103.80）	0.8920
I²（%）	73.7	85.4	88.0	75.6	81.1
P值	0.0098	0.0001	0	0.0064	0.0012

Please choose a citation manager

Content to export