Soluble Programmed Cell Death Protein 1 and Its Ligand: Potential Biomarkers to Predict Acute Kidney Injury After Surgery in Critically Ill Patients

Abstract

Jingyi Wang, Xi Zheng, Yijia Jiang, Huimiao Jia, Xiaocui Shi, Yue Han, Qingping Li, Wenxiong Li Surgical Intensive Care Unit, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Wenxiong Li, Surgical Intensive Care Unit, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel [phone], Email [email protected]: Programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have been detected in injury kidney. However, their expressions are unclear in mice kidneys under renal ischemia-reperfusion injury (IRI). In this study, we would observe the expressions of PD-1 and PD-L1 in kidney tissues and analyze the association between the concentrations of PD-1 and PD-L1 in mouse kidney homogenate and the corresponding concentrations of soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1) in plasma after renal IRI. Further, we explored the predictive value of sPD-1 and sPD-L1 for acute kidney injury (AKI) in high-risk patients after surgery.Methods: This study established an AKI model induced by IRI in mice. Plasma, kidney samples, and homogenate were collected 0h, 24h, and 48h after surgery for immunohistochemistry and enzyme-linked immunosorbent assay. Then, we continuously enrolled 88 AKI high-risk patients who underwent noncardiac surgery. The biomarkers, including sPD-1, sPD-L1, and urine neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), were detected immediately after surgery.Results: Our data revealed the concentrations of PD-1 and PD-L1 in kidney homogenate, and sPD-1 and sPD-L1 in plasma significantly increased at 0h, 24h, and 48h after IRI. A positive association was found between PD-1 and sPD-1 (r = 0.774, p < 0.001), and between PD-L1 and sPD-L1 (r = 0.881, p < 0.001). Compared to NGAL, [TIMP-2]*[IGFBP7], sPD-1 and sPD-L1 showed better predictive abilities for AKI with an area under the ROC curve of 0.856 (95% confidence interval [CI]: 0.825– 0.958, p < 0.001) and 0.906 (95% CI: 0.764– 0.921, p < 0.001).Conclusion: The increased expressions of PD-1 and PD-L1 in kidneys under IRI suggested they may play essential roles in AKI development. sPD-1 and sPD-L1 can indirectly reflect the expressions of PD-1 and PD-L1 in kidneys, respectively. sPD-1 and sPD-L1 showed excellent predictive ability for AKI in high-risk patients.Keywords: acute kidney injury, ischemia-reperfusion injury, programmed cell death protein 1, programmed death-ligand 1

Keywords

• acute kidney injury
• ischemia-reperfusion injury
• programmed cell death protein 1
• programmed death-ligand 1