POS-081 SERUM RESPONSE FACTOR, A NOVEL EARLY DIAGNOSTIC BIOMARKER OF ACUTE KIDNEY INJURY

Abstract

Studies have shown that serum response factor (SRF) is increased in chronic kidney injury, such as diabetic nephropathy, hyperuricemic nephropathy and renal cell carcinoma. The objective is to explore the early diagnostic value of SRF in acute kidney injury (AKI). AKI-related microarray data were analyzed, and the expression and location of SRF were investigated in the early phase of AKI. ① The microarray analysis results of bilateral I/R mice There were 567 DEGs at 2 h and 857 DEGs at 4 h after I/R in GSE98622 (Figure 1A, 1B). SRF started to increase at 2 h-4 h and decreased to the basal level at 72 h after bilateral I/R in mice (Figure 1C), which suggested that SRF might be connected with AKI. Moreover, as shown in Figure 1C, SRF was increased again 7 d after I/R, which indicated that SRF might be a promising biomarker of the transformation from AKI to chronic kidney injury and post-AKI fibrosis. ② SRF was upregulated and localized in TECs in I/R rats As shown by IHC and IF, SRF was upregulated and located in TECs 6 h after I/R compared to the sham operation group and the control group (Figure 2). This result was consistent with the microarray data from I/R mice. ③ Scr level and renal SRF mRNA expression in I/R rats As shown in Figure 3A, the expression of SRF mRNA in the kidney changed 1 h, 3 h, 6 h, 9 h, 12 h, and 24 h after I/R. In other words, the SRF level in the kidney of the I/R rats started to increase after 3 h, reached its peak at 6-9 h and decreased at 12 h and 24 h. The fitting function estimated that the peak SRF level should be at 6 h. No significant variation in SRF was detected in the sham operation group (Figure 3A). Compared to the increase in SRF levels, the increase in Scr levels was obviously delayed. Scr started to increase after 24 h in the I/R group compared to the control group and the sham group (Figure 3B), indicating that SRF may be an earlier biomarker for AKI and may assist physicians in diagnosing AKI in a timelier manner. ④ The protein level of SRF in kidney, urine and serum in vivo SRF levels in the kidney increased at 1 h, reached its peak at 6 h and started to decline at 12 h after I/R (Figure 4A, 4B). SRF was dramatically increased in the serum of I/R rats at 1 h-6 h after I/R (Figure 4C). In urine, the expression of SRF in the I/R group was dramatically increased at 3 h, reached its peak at 6-9 h, and began to decrease at 12 h after I/R. Additionally, SRF levels were also increased postoperatively in the kidney, urine and serum of the sham rats, but the increases in the sham group were significantly less than those in the I/R group. ⑤ The ROC curve of renal SRF mRNA, renal SRF protein, urinary SRF, serum SRF and Scr in early (before 24 h) AKI To explore more sensitive and specific biomarkers to diagnose AKI, we used a ROC curve assay to investigate the cutoff value of renal SRF mRNA, renal SRF protein, urinary SRF, serum SRF, and Scr levels (Figure 5). The AUCs of SRF mRNA, SRF protein, urinary SRF and serum SRF were 87.9%, 83%, 81.3% and 78.8%, respectively, which were all better than that of Scr (68.8%), which indicated that urinary SRF could be an early diagnostic marker of AKI with better sensitivity and specificity than Scr. SRF is remarkably upregulated in early (before 24 h) AKI and can replace Scr as a potential new early diagnostic biomarker of AKI.