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Kidney Week

Abstract: PO0224

A Novel Renoprotective Strategy: Upregulation of PD-L1 Expression Mitigates Cisplatin-Induced AKI

Session Information

  • AKI Mechanisms - 3
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Zhang, Jun, University of California, Davis, Davis, California, United States
  • Gu, Shenwen V., University of California, Davis, Davis, California, United States
  • Hsu, Ssu-Wei, University of California, Davis, Davis, California, United States
  • Chen, Ching-Hsien, University of California, Davis, Davis, California, United States

Cisplatin is an effective chemotherapeutic agent against various types of cancers; however, the use of cisplatin is associated with a major side-effect of nephrotoxicity, resulting in acute kidney injury (AKI). Growing evidence suggests that programmed death-1(PD-1)/programmed death ligand (PD-L1) immune checkpoint signaling plays a critical role in mediating inflammatory responses and immune homeostasis. While PD-L1 has emerged as a promising target for immunotherapy, little is known concerning how PD-L1 is regulated. In this study, we aimed to determine the expression and contribution of PD-L1 in cisplatin-induced AKI.


PD-L1 expression in kidney cells and tissues were determined by immunohistochemistry (IHC), real-time polymerase chain reaction and western blot assays. PD-L1-containing lentiviruses were subcapsularly injected into the kidneys of mice. 7 days after the injection, mice were intraperitoneally treated with cisplatin for 3 days and subjected to kidney function tests. High-dimensional single-cell mass spectrometry was used to reveal immune profiling and discover the underlying immunological mechanisms of PD-L1 in an AKI mouse model.


IHC staining of PD-L1 shows a significantly lower intensity of staining and less stained proximal tubule epithelial cells in cisplatin-exposed mice tissues than that in the PBS controls. Next, we demonstrate that cisplatin exposure decreased mRNA expression and protein levels of PD-L1 in primary renal proximal tubular epithelial cells and this inhibition appeared to be dose-dependent. Interestingly, we also find a decrease in PD-L1 expression with a concomitant increase in pro-inflammatory cytokines in response to cisplatin. Mass spectrometry analyses reveal cisplatin-induced multiple pro-inflammatory leukocytes infiltration in kidneys. Through genetically engineered kidney tissues in mice, ectopic expression PD-L1 in kidneys was able to suppress leukocytes infiltration and pro-inflammatory cytokines. In addition, both serum creatinine and blood urea nitrogen levels were significantly reduced in cisplatin-treated mice with PD-L1 overexpression.


Our data suggest a renoprotective effect of PD-L1 upregulation on cisplatin-induced AKI and also provide an alternative therapeutic strategy against nephrotoxicity.


  • Other U.S. Government Support