Objective To analyze the relationship between serum fibroblast growth factor (FGF)-2 and FGF-23 levels and renal function and its short-term prognosis in sepsis patients with acute kidney injury (AKI) and treated by continuous renal replacement therapy (CRRT). Methods A total of 157 sepsis patients complicated with AKI and treated by CRRT were enrolled in this study. Serum FGF-2 and FGF-23 levels were compared among patients with different AKI stage. Patients were divided into survival group and death group according to the prognosis at day 28. Serum FGF-2 and FGF-23 levels and renal function indexes were compared between the two groups, and the correlations were analyzed. The predictive value of serum FGF-2 and FGF-23 levels for short-term prognosis of AKI was evaluated. Results In patients with AKI Ⅲ, serum FGF-2 level was lower and serum FGF-23 level was higher, as compared those with AKI Ⅱ (t=20.149 and -8.060, P<0.001). Serum FGF-23, creatinine (Scr) and cystatin C levels were higher in the death group than in the survival group, while serum FGF-2 and eGFR were lower in the death group than in the survival group (t=-12.051, -17.462, -5.881, 25.990 and 15.997 respectively; P<0.001). Pearson correlation analysis showed that serum FGF-2 was negatively correlated with Scr and cystatin C, and positively correlated with eGFR (r=-0.511, -0.449 and 0.606 respectively; P<0.001, 0.002 and <0.001 respectively). Serum FGF-23 was positively correlated with Scr and cystatin C, and negatively correlated with eGFR (r=0.610, 0.522, -0.654 respectively; P<0.001). The predictive value of combined application of serum FGF-2 and FGF-23 levels was higher than that of the two indicators applied individually (Z=2.120 and 2.034, P=0.034 and 0.042). Conclusion Serum FGF-2 level is significantly reduced and FGF-23 level is significantly increased in sepsis patients with AKI. The lower serum FGF-2 level and higher serum FGF-23 level are associated with the decreased renal function and poor short-term prognosis. Simultaneous use of serum FGF-2 and FGF-23 levels improves the prediction value for short-term prognosis in sepsis patients with AKI.
[1]Oczkowski S, Alshamsi F, Belley-Cote E, et al. Surviving Sepsis Campaign Guidelines 2021: highlights for the practicing clinician[J]. Pol Arch Intern Med, 2022, 132(7-8):16290.
[2] 盛松, 张艳虹, 马杭琨, 等. 脓毒症合并急性肾损伤并接受连续肾脏替代治疗患者28d死亡预测模型构建与验证[J]. 创伤与急危重病医学, 2021, 9(3):200-205,210.
[3]Chen WY, Cai LH, Zhang ZH, et al. The timing of continuous renal replacement therapy initiation in sepsis-associated acute kidney injury in the intensive care unit: the CRTSAKI Study (Continuous RRT Timing in Sepsis-associated AKI in ICU): study protocol for a multicentre, randomised controlled trial[J]. BMJ Open, 2021, 11(2):e040718.
[4]彭霞, 夏悦, 杨艺娇, 等. 成纤维细胞生长因子2在纤维化疾病中表达的研究进展[J]. 中国医药, 2022, 17(2):305-307.
[5]Sun Y, Ye F, Li D, et al. Fibroblast growth factor 2 (FGF2) ameliorates the coagulation abnormalities in sepsis[J]. Toxicol Appl Pharmacol, 2023, 460:116364.
[6]Portales-Castillo I, Simic P. PTH, FGF-23, Klotho and Vitamin D as regulators of calcium and phosphorus: Genetics, epigenetics and beyond[J]. Front Endocrinol (Lausanne), 2022, 13:992666.
[7]Pei Y, Zhou G, Wang P, et al. Serum cystatin C, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, klotho and fibroblast growth factor-23 in the early prediction of acute kidney injury associated with sepsis in a Chinese emergency cohort study[J]. Eur J Med Res, 2022, 27(1):39.
[8]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.
[9]郭锦洲. 改善全球肾脏病预后组织(KDIGO)临床实践指南:急性肾损伤[J]. 肾脏病与透析肾移植杂志, 2013, 22(1):57-60.
[10]Quan H, Li B, Couris CM, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries[J]. Am J Epidemiol, 2011, 173(6):676-682.
[11]李波, 邵素花, 万娅莉, 等. 血清尿调节素、肝素结合蛋白、Klotho蛋白联合APACHE Ⅱ评分对脓毒症并发急性肾损伤患者28天预后的评估价值[J]. 现代生物医学进展, 2022, 22(16):3107-3111, 3152.
[12]Yang Y, Dong J, Chen X, et al. Incidence, risk factors and clinical outcomes of septic acute renal injury in cancer patients with sepsis admitted to the ICU: A retrospective study[J]. Front Med (Lausanne), 2022, 9:1015735.
[13]易雪琳, 欧阳亮, 庹玲. 血清CysC、UmAlb、Scr在脓毒症合并急性肾损伤患者中的表达及疾病预测价值[J]. 国际泌尿系统杂志, 2022, 42(1):72-76.
[14]Tamburello M, Altieri B, Sbiera I, et al. FGF/FGFR signaling in adrenocortical development and tumorigenesis: novel potential therapeutic targets in adrenocortical carcinoma[J]. Endocrine, 2022, 77(3):411-418.
[15]Xu Z, Zhu X, Wang M, et al. FGF/FGFR2 Protects against Tubular Cell Death and Acute Kidney Injury Involving Erk1/2 Signaling Activation[J]. Kidney Dis (Basel), 2020, 6(3):181-194.
[16]Tan XH, Zheng XM, Yu LX, et al. Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling[J]. J Cell Mol Med, 2017, 21(11):2909-2925.
[17]Pan X, Xu S, Zhou Z, et al. Fibroblast growth factor-2 alleviates the capillary leakage and inflammation in sepsis[J]. Mol Med, 2020, 26(1):108.
[18]Lin J, Lin L, Chen S, et al. Serum fibroblast growth factor 23 (FGF-23): associations with hyperphosphatemia and clinical staging of feline chronic kidney disease[J]. J Vet Diagn Invest, 2021, 33(2):288-293.
[19]Tao W, Guo SW, Fan YJ, et al. Prediction of Acute Kidney Injury by Fibroblast Growth Factor 23 (FGF-23) in Adult Patients, A Meta-analysis Study[J]. Iran J Kidney Dis, 2023, 1(1):1-8.
[20]Huang SS, Huang PH, Leu HB, et al. Significance of serum FGF-23 for risk assessment of contrast-associated acute kidney injury and clinical outcomes in patients undergoing coronary angiography[J]. PLoS One, 2021, 16(7):e0254835.
[21]许书添. 成纤维细胞生长因子23与急性肾损伤[J]. 肾脏病与透析肾移植杂志, 2018, 27(6):560-564.
[22]盛松, 张艳虹, 马杭琨, 等. 查尔森合并症指数对合并急性肾损伤并接受连续肾脏替代治疗的脓毒症患者死亡风险的评估价值[J]. 临床急诊杂志, 2021, 22(11):764-771.
[23]Livingston MJ, Shu S, Fan Y, et al. Tubular cells produce FGF2 via autophagy after acute kidney injury leading to fibroblast activation and renal fibrosis[J]. Autophagy, 2023, 19(1):256-277.
[24]Zhou W, Simic P, Rhee EP. Fibroblast Growth Factor 23 Regulation and Acute Kidney Injury[J]. Nephron, 2022, 146(3):239-242.
[25]Kamr AM, Dembek KA, Hildreth BE, et al. The FGF-23/klotho axis and its relationship with phosphorus, calcium, vitamin D, PTH, aldosterone, severity of disease, and outcome in hospitalised foals[J]. Equine Vet J, 2018, 50(6):739-746.