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

Abstract

Purpose 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.

PD-L1 as a Urine Biomarker in Renal Cell Carcinoma—A Case Series and Proof-of-Concept Study

“…Furthermore, urine PD-L1 has been reported in the context of non-malignant renal conditions such as acute kidney injury or nephrotic syndrome [33][34][35].…”

Soluble Programmed Cell Death 1 Protein Is a Promising Biomarker to Predict Severe Liver Inflammation in Chronic Hepatitis B Patients

“…sPD-1 is produced by the activated peripheral blood mononuclear cells (PBMCs) through the expression of alternative spliced PD-1 mRNA transcript PD-1Δex3 . Recent studies have shown that sPD-1 is elevated in infectious, inflammatory, and autoimmune diseases and associated with the disease activity. − In chronic HBV infection, sPD-1 is also elevated and correlates with the levels of liver enzymes and the virological response. Besides, high sPD-1 levels were demonstrated to be associated with a high risk of developing HCC. − These results suggest that sPD-1 may be associated with disease activity and is involved in disease progression in chronic HBV infections.…”

“… 15 Recent studies have shown that sPD-1 is elevated in infectious, inflammatory, and autoimmune diseases and associated with the disease activity. 16 − 19 In chronic HBV infection, sPD-1 is also elevated and correlates with the levels of liver enzymes and the virological response. Besides, high sPD-1 levels were demonstrated to be associated with a high risk of developing HCC.…”

Soluble Programmed Cell Death 1 Protein is a Promising Biomarker to Predict Severe Liver Inflammation in Chronic Hepatitis B Patients

“…15 Recent studies have shown that sPD-1 is elevated in infectious, in ammatory and autoimmune diseases and associated with the disease activity. [16][17][18][19] In chronic HBV infection, sPD-1 is also elevated and correlates with the levels of liver enzymes and virological response. Besides, high sPD-1 levels were demonstrated to associated with a high risk of developing HCC.…”