Predictive model for postoperative acute kidney injury after coronary artery bypass grafting based on the abnormal expression of uromodulin and TNF receptor-associated factor 6_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

QI Yujuan ¹ , LIU Shenyue ² , LI Shuning ¹ , BAI Yaobang ¹ , ZHU Xiaolong ³ , FU Bo ³ ,  WU Zhenhua ¹

1. Department of Intensive Care Medicine, Tianjin University Tianjin Chest Hospital, Tianjin, 300222, P. R. China;
2. Shandong First Medical University, Jinan, 250021, P. R. China;
3. Department of Cardiac Surgery, Tianjin University Tianjin Chest Hospital, Tianjin, 300222, P. R. China;

Corresponding author：

WU Zhenhua, Email: wzh8306@aliyun.com

Keywords：

Coronary artery bypass grafting; acute kidney injury; uromodulin; tumor necrosis factor receptor-associated factor 6; predictive model

DOI：

10.7507/1007-4848.202504102

Video：

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Objective To construct a predictive model for acute kidney injury (AKI) after coronary artery bypass grafting (CABG) based on uromodulin (UMOD) and tumor necrosis factor receptor-associated factor 6 (TRAF6). Methods Patients undergoing CABG treatment at Tianjin Chest Hospital from 2022 to 2024 were prospectively enrolled. Based on whether they developed AKI post-surgery, patients were divided into the an AKI group and a non-AKI group. Differences in UMOD, TRAF6, blood urea nitrogen (BUN), serum creatinine (SCr), β-N-acetylglucosaminidase (NAG), and SCr clearance rate at different time points were compared between the two groups. Predictive models for AKI after CABG were constructed at various time points, and the predictive efficacy of the models for AKI was analyzed. Results A total of 70 patients were included, with 22 in the AKI group [13 males and 9 females, aged 55-72 (67.91±4.91) years] and 48 in the non-AKI group [32 males and 16 females, aged 56-72 (68.07±4.67) years]. The UMOD levels in the AKI group were lower than those in the non-AKI group at various time points including before surgery (t=34.283, P<0.001), postoperative 2 h (t=29.590, P<0.001), 4 h (t=30.705, P<0.001), 8 h (t=26.620, P<0.001), 12 h (t=29.671, P<0.001), and 24 h (t=31.397, P<0.001). The TRAF6 levels in the AKI group were higher than those in the non-AKI group at all these time points (P<0.001). Multivariate analysis showed that higher levels of TRAF6, BUN, SCr, NAG, and lower levels of UMOD and SCr clearance rate were risk factors for AKI after CABG (P<0.05). The receiver operating characteristic curve analysis showed that the area under the curve of the predictive model at postoperative 12 h was significantly higher than that of the remaining models. The risk of AKI after CABG was: log (Y)=12.333−1.582×UMOD+1.270×TRAF6+1.356×BUN+1.356×SCr+1.355×NAG−1.254×SCr clearance rate. Conclusion In the occurrence process of AKI after CABG, TRAF6 exacerbates renal injury by activating inflammatory signals and promoting cell apoptosis, while UMOD alleviates renal injury by regulating renal tubular function and protecting renal tubular epithelial cells. Through the simulation analysis of the two biomarkers combined with renal injury indicators at postoperative 12 h, the occurrence of AKI after CABG can be effectively predicted.

1.	张舒, 许珊, 秦开秀, 等. 冠脉搭桥术后发生早期急性肾损伤的风险评估. 重庆医科大学学报, 2022, 47(8): 963-969.Zhang S, Xu S, Qin KX, et al. Risk assessment of early acute kidney injury after coronary artery bypass grafting. J Chongqing Med Univ, 2022, 47(8): 963-969.
2.	王春丽, 孙骁, 王凤丹, 等. 非体外循环下冠脉搭桥术后急性肾损伤的危险因素及术前尿酸、白蛋白的预测价值分析. 现代生物医学进展, 2021, 21(8): 1442-1447.Wang CL, Sun X, Wang FD, et al. Analysis of risk factors for acute kidney injury after off-pump coronary artery bypass grafting and the predictive value of preoperative uric acid and albumin. Adv Mod Biomed, 2021, 21(8): 1442-1447.
3.	张小琼, 陈明, 廖江铨, 等. 他汀类药物非降脂作用治疗心肾综合征的机制探讨. 中日友好医院学报, 2020, 34(1): 39-41,44.Zhang XQ, Chen M, Liao JQ, et al. Discussion on the mechanism of statins' non-lipid-lowering effects in the treatment of cardiorenal syndrome. J China-Japan Friendship Hosp, 2020, 34(1): 39-41,44.
4.	Abbasi MSR, Sultan K, Manzoor R, et al. Assessment of renal function and prevalence of acute kidney injury following coronary artery bypass graft surgery and associated risk factors: A retrospective cohort study at a tertiary care hospital in Islamabad, Pakistan. Medicine, 2023, 102(42): e35482.
5.	Oh TK, Song IA. Postoperative acute kidney injury requiring continuous renal replacement therapy and outcomes after coronary artery bypass grafting: a nationwide cohort study. J Cardiothorac Surg, 2021, 16(1).
6.	Wintgen L, Dakkak AR, Al Shakaki M, et al. Acute kidney injury following coronary artery bypass grafting and control angiography: a comprehensive analysis of 221 patients. Heart Vessels, 2021, 36(1): 1-6.
7.	Grins E, Ederoth P, Bjursten H, et al. Effect of cyclosporine on cytokine production in elective coronary artery bypass grafting: A sub-analysis of the CiPRICS (Cyclosporine to Protect Renal Function in Cardiac Surgery) Study. J Cardiothorac Vasc Anesth, 2022, 36(7): 1985-1994.
8.	Nam JS, Kim WJ, Seo WW, et al. Effects of balanced versus saline-based solutions on acute kidney injury in off-pump coronary artery bypass surgery: A randomized controlled trial. J Cardiothorac Vasc Anesth, 2024, 38(9): 1923-1931.
9.	Greco K, Varelmann D, Patel J. Anesthetic management of a Jehovah's Witness patient for coronary artery bypass grafting with antiphospholipid antibody syndrome and renal transplant. Semin Cardiothorac Vasc Anesth, 2024, 28(3): 177-180.
10.	中国动脉化冠状动脉旁路移植术专家共识组. 中国动脉化冠状动脉旁路移植术专家共识2019版. 中华胸心血管外科杂志, 2019, 35(4): 193-200.Expert Consensus Group on Arterial Coronary Artery Bypass Grafting in China. Expert consensus on arterial coronary artery bypass grafting in China 2019 edition. Chin J Thorac Cardiovasc Surg, 2019, 35(4): 193-200.
11.	贾士杰, 宋铁鹰, 贾明. 心脏手术后急性肾损伤. 心肺血管病杂志, 2011, 30(2): 168-171.Jia SJ, Song TY, Jia M. Acute kidney injury after cardiac surgery. J Cardiopulm Vasc Dis, 2011, 30(2): 168-171.
12.	Choi JS, Yun D, Kim DK, et al. Hyperchloremia is associated with poor renal outcome after coronary artery bypass grafting. BMC Nephrol, 2021, 22(1).
13.	Aghakouchakzadeh M, Hosseini K, Haghjoo M, et al. Empagliflozin to prevent post-operative atrial fibrillation in patients undergoing coronary artery bypass graft surgery. PACE, 2024, 47(8): 1087-1095.
14.	Hwang B, Williams ML, Tian DH, et al. Coronary artery bypass surgery for acute coronary syndrome: A network meta-analysis of on-pump cardioplegic arrest, off-pump, and on-pump beating heart strategies. J Card Surg, 2022, 37(12): 5290-5299.
15.	Nellipudi JA, Baker RA, Dykes L, et al. Prognostic value of high-sensitivity troponin T after on-pump coronary artery bypass graft surgery. Heart Lung Circ, 2021, 30(10): 1562-1569.
16.	Salahuddin AP, Chowdhury AT, Magdum M, et al. Preoperative serum albumin levels and postoperative acute kidney injury in off-pump coronary artery bypass surgery: A single-center study in Bangladesh. World J Cardiovasc Surg, 2024, 14(8): 131-144.
17.	Javaherforooshzadeh F, Shaker Z, Rashidi M, et al. The effect of N-acetyl cysteine injection on renal function after coronary artery bypass graft surgery: a randomized double blind clinical trial. J Cardiothorac Surg, 2021, 16(1).
18.	Tian Y, Yang Z, Liu P, et al. Circ0001714 knockdown alleviates lipopolysaccharide-induced apoptosis and inflammation in renal tubular epithelial cells via miR-129-5p/TRAF6 axis in septic acute kidney injury. J Bioenerg Biomembr, 2023, 55(4): 289-300.
19.	Lu W, Boranyi B, Zhang D, et al. The novel biomarker circ0020339 drives septic acute kidney injury by targeting miR-17-5p/IPMK axis. Int Urol Nephrol, 2022, 55(2): 437-448.
20.	Ma J, Li Y, Zhang S, et al. MiR-590-3p attenuates acute kidney injury by inhibiting tumor necrosis factor receptor-associated factor 6 in septic mice. Inflammation, 2019, 42(2): 637-649.
21.	Vonbrunn E, Ebert N, Cordasic N, et al. Serum uromodulin as early marker for ischemic acute kidney injury and nephron loss: association with kidney tissue distribution pattern. J Transl Med, 2025, 23(1): 323.
22.	Decker SS, Obeid W, Hsu J, et al. The development of lateral flow devices for urinary biomarkers to assess kidney health. Sci Rep, 2024, 14(1): 8516.
23.	Fretes VN, Rosenber LM, Monica EME, et al. WCN24-2395 familial global and focal glomerulosclerosis: autosomal dominant tubulointerstitial kidney disease (ADTKD) due to C. 610C>G mutation in UMOD gene. Kidney Int Rep, 2024, 9(4S): S351-S352.
24.	Aguilar C GJ, Flores R DL, Aguilar C RK, et al. Autosomic dominant tubulo interstitial kidney disease: Case report of a new variant of the UMOD gene. G Ital Nefrol, 2023, 40(5): 11-12.
25.	AbdelHady EA, Vaughan EL, Thomas S, et al. Longitudinal effects of a common UMOD variant on kidney function, blood pressure, cognitive and physical function in older women and men. J Hum Hypertens, 2023, 37(8): 709-717.
26.	Villalobos NP, Lopez D CC, Orellana C V, et al. UMOD-related autosomal dominant tubulointerstitial kidney disease: an unfavourable novel mutation. Nefrologia, 2023, 43(3): 378-380.
27.	Olinger E, Schaeffer C, Kessler K, et al. An intermediate-effect size variant in UMOD confers risk for chronic kidney disease. Proc Natl Acad Sci USA, 2022, 119(33): e2114734119.
28.	Vaughan EL, AbdelHadyEA, Thomas S, et al. Effect of a common UMOD variant on kidney function, blood pressure, cognitive and physical function in a community-based cohort of older adults. J Hum Hypertens, 2021, 36(11): 983-988.
29.	Onoe T, Hoshino S, Yonemoto K, et al. Significance of kidney biopsy in autosomal dominant tubulointerstitial kidney disease-UMOD: is kidney biopsy truly nonspecific? BMC Nephrol, 2021, 22(1).

1. 张舒, 许珊, 秦开秀, 等. 冠脉搭桥术后发生早期急性肾损伤的风险评估. 重庆医科大学学报, 2022, 47(8): 963-969.Zhang S, Xu S, Qin KX, et al. Risk assessment of early acute kidney injury after coronary artery bypass grafting. J Chongqing Med Univ, 2022, 47(8): 963-969.
2. 王春丽, 孙骁, 王凤丹, 等. 非体外循环下冠脉搭桥术后急性肾损伤的危险因素及术前尿酸、白蛋白的预测价值分析. 现代生物医学进展, 2021, 21(8): 1442-1447.Wang CL, Sun X, Wang FD, et al. Analysis of risk factors for acute kidney injury after off-pump coronary artery bypass grafting and the predictive value of preoperative uric acid and albumin. Adv Mod Biomed, 2021, 21(8): 1442-1447.
3. 张小琼, 陈明, 廖江铨, 等. 他汀类药物非降脂作用治疗心肾综合征的机制探讨. 中日友好医院学报, 2020, 34(1): 39-41,44.Zhang XQ, Chen M, Liao JQ, et al. Discussion on the mechanism of statins' non-lipid-lowering effects in the treatment of cardiorenal syndrome. J China-Japan Friendship Hosp, 2020, 34(1): 39-41,44.
4. Abbasi MSR, Sultan K, Manzoor R, et al. Assessment of renal function and prevalence of acute kidney injury following coronary artery bypass graft surgery and associated risk factors: A retrospective cohort study at a tertiary care hospital in Islamabad, Pakistan. Medicine, 2023, 102(42): e35482.
5. Oh TK, Song IA. Postoperative acute kidney injury requiring continuous renal replacement therapy and outcomes after coronary artery bypass grafting: a nationwide cohort study. J Cardiothorac Surg, 2021, 16(1).
6. Wintgen L, Dakkak AR, Al Shakaki M, et al. Acute kidney injury following coronary artery bypass grafting and control angiography: a comprehensive analysis of 221 patients. Heart Vessels, 2021, 36(1): 1-6.
7. Grins E, Ederoth P, Bjursten H, et al. Effect of cyclosporine on cytokine production in elective coronary artery bypass grafting: A sub-analysis of the CiPRICS (Cyclosporine to Protect Renal Function in Cardiac Surgery) Study. J Cardiothorac Vasc Anesth, 2022, 36(7): 1985-1994.
8. Nam JS, Kim WJ, Seo WW, et al. Effects of balanced versus saline-based solutions on acute kidney injury in off-pump coronary artery bypass surgery: A randomized controlled trial. J Cardiothorac Vasc Anesth, 2024, 38(9): 1923-1931.
9. Greco K, Varelmann D, Patel J. Anesthetic management of a Jehovah's Witness patient for coronary artery bypass grafting with antiphospholipid antibody syndrome and renal transplant. Semin Cardiothorac Vasc Anesth, 2024, 28(3): 177-180.
10. 中国动脉化冠状动脉旁路移植术专家共识组. 中国动脉化冠状动脉旁路移植术专家共识2019版. 中华胸心血管外科杂志, 2019, 35(4): 193-200.Expert Consensus Group on Arterial Coronary Artery Bypass Grafting in China. Expert consensus on arterial coronary artery bypass grafting in China 2019 edition. Chin J Thorac Cardiovasc Surg, 2019, 35(4): 193-200.
11. 贾士杰, 宋铁鹰, 贾明. 心脏手术后急性肾损伤. 心肺血管病杂志, 2011, 30(2): 168-171.Jia SJ, Song TY, Jia M. Acute kidney injury after cardiac surgery. J Cardiopulm Vasc Dis, 2011, 30(2): 168-171.
12. Choi JS, Yun D, Kim DK, et al. Hyperchloremia is associated with poor renal outcome after coronary artery bypass grafting. BMC Nephrol, 2021, 22(1).
13. Aghakouchakzadeh M, Hosseini K, Haghjoo M, et al. Empagliflozin to prevent post-operative atrial fibrillation in patients undergoing coronary artery bypass graft surgery. PACE, 2024, 47(8): 1087-1095.
14. Hwang B, Williams ML, Tian DH, et al. Coronary artery bypass surgery for acute coronary syndrome: A network meta-analysis of on-pump cardioplegic arrest, off-pump, and on-pump beating heart strategies. J Card Surg, 2022, 37(12): 5290-5299.
15. Nellipudi JA, Baker RA, Dykes L, et al. Prognostic value of high-sensitivity troponin T after on-pump coronary artery bypass graft surgery. Heart Lung Circ, 2021, 30(10): 1562-1569.
16. Salahuddin AP, Chowdhury AT, Magdum M, et al. Preoperative serum albumin levels and postoperative acute kidney injury in off-pump coronary artery bypass surgery: A single-center study in Bangladesh. World J Cardiovasc Surg, 2024, 14(8): 131-144.
17. Javaherforooshzadeh F, Shaker Z, Rashidi M, et al. The effect of N-acetyl cysteine injection on renal function after coronary artery bypass graft surgery: a randomized double blind clinical trial. J Cardiothorac Surg, 2021, 16(1).
18. Tian Y, Yang Z, Liu P, et al. Circ0001714 knockdown alleviates lipopolysaccharide-induced apoptosis and inflammation in renal tubular epithelial cells via miR-129-5p/TRAF6 axis in septic acute kidney injury. J Bioenerg Biomembr, 2023, 55(4): 289-300.
19. Lu W, Boranyi B, Zhang D, et al. The novel biomarker circ0020339 drives septic acute kidney injury by targeting miR-17-5p/IPMK axis. Int Urol Nephrol, 2022, 55(2): 437-448.
20. Ma J, Li Y, Zhang S, et al. MiR-590-3p attenuates acute kidney injury by inhibiting tumor necrosis factor receptor-associated factor 6 in septic mice. Inflammation, 2019, 42(2): 637-649.
21. Vonbrunn E, Ebert N, Cordasic N, et al. Serum uromodulin as early marker for ischemic acute kidney injury and nephron loss: association with kidney tissue distribution pattern. J Transl Med, 2025, 23(1): 323.
22. Decker SS, Obeid W, Hsu J, et al. The development of lateral flow devices for urinary biomarkers to assess kidney health. Sci Rep, 2024, 14(1): 8516.
23. Fretes VN, Rosenber LM, Monica EME, et al. WCN24-2395 familial global and focal glomerulosclerosis: autosomal dominant tubulointerstitial kidney disease (ADTKD) due to C. 610C>G mutation in UMOD gene. Kidney Int Rep, 2024, 9(4S): S351-S352.
24. Aguilar C GJ, Flores R DL, Aguilar C RK, et al. Autosomic dominant tubulo interstitial kidney disease: Case report of a new variant of the UMOD gene. G Ital Nefrol, 2023, 40(5): 11-12.
25. AbdelHady EA, Vaughan EL, Thomas S, et al. Longitudinal effects of a common UMOD variant on kidney function, blood pressure, cognitive and physical function in older women and men. J Hum Hypertens, 2023, 37(8): 709-717.
26. Villalobos NP, Lopez D CC, Orellana C V, et al. UMOD-related autosomal dominant tubulointerstitial kidney disease: an unfavourable novel mutation. Nefrologia, 2023, 43(3): 378-380.
27. Olinger E, Schaeffer C, Kessler K, et al. An intermediate-effect size variant in UMOD confers risk for chronic kidney disease. Proc Natl Acad Sci USA, 2022, 119(33): e2114734119.
28. Vaughan EL, AbdelHadyEA, Thomas S, et al. Effect of a common UMOD variant on kidney function, blood pressure, cognitive and physical function in a community-based cohort of older adults. J Hum Hypertens, 2021, 36(11): 983-988.
29. Onoe T, Hoshino S, Yonemoto K, et al. Significance of kidney biopsy in autosomal dominant tubulointerstitial kidney disease-UMOD: is kidney biopsy truly nonspecific? BMC Nephrol, 2021, 22(1).

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Latest ArticlesPredictive model for postoperative acute kidney injury after coronary artery bypass grafting based on the abnormal expression of uromodulin and TNF receptor-associated factor 6

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