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ORIGINAL RESEARCH article

Front. Med.
Sec. Nephrology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1530804
This article is part of the Research Topic Innovative Therapeutic Strategies for Chronic Kidney Disease: From Molecular Mechanisms to Clinical Practice View all 3 articles

Increased Serum Soluble PD-L1 Levels in Patients with Advanced Stages of Chronic Kidney Disease

Provisionally accepted
Ayaka Hayashi Ayaka Hayashi Hiroto Ishihara Hiroto Ishihara Mayuko Kawabe Mayuko Kawabe Kazuhiko Kato Kazuhiko Kato Akio Nakashima Akio Nakashima Izumi Yamamoto Izumi Yamamoto Teppei Sakano Teppei Sakano Hiroe Kobashi Hiroe Kobashi Makoto Morita Makoto Morita Takashi Yokoo Takashi Yokoo Mitsuyoshi Urashima Mitsuyoshi Urashima *
  • Jikei University Hospital, Minato, Japan

The final, formatted version of the article will be published soon.

    Background: Programmed death-ligand 1 (PD-L1) is overexpressed on renal tubular and vascular epithelial cells in inflammatory kidney diseases as well as on aged kidney podocytes, contributing to chronic kidney disease (CKD) progression. The association of serum soluble programmed death-ligand 1 (sPD-L1) levels and chronic kidney disease (CKD) progression is unknown.Methods: To compare serum sPD-L1 levels among healthy individuals and patients with various CKD stages, including those undergoing dialysis, a secondary analysis was performed using clinical data and residual serum samples from four distinct cohorts, each prospectively collected for different research purposes: The Vaccine Cohort (2021-2022), the Cancer Cohort (2010-2018), the Dialysis Initiation Cohort (2023-2024), and the Dialysis Maintenance Cohort (2011-2015) included patients on stable maintenance dialysis.Results: The study analyzed serum sPD-L1 levels in 2,829 participants (mean age, 54.2 years; male, 54.2%) across the four cohorts. In the Vaccine and Cancer cohorts, sPD-L1 levels increased significantly with age (P<0.001) and male sex (P<0.001). In the Vaccine Cohort, elevated median sPD-L1 levels (pg/mL) were significantly associated with CKD stage progression (P<0.001), showing exponentially higher levels with CKD progression. A similar association was observed and validated in the Cancer Cohort (P<0.001). In the Dialysis Initiation Cohort (n=15), sPD-L1 levels significantly increased three months after dialysis initiation compared to pre-dialysis levels (P=0.03). In the Dialysis Maintenance Cohort, sPD-L1 levels increased with longer dialysis duration (P<0.001).Conclusions: Serum sPD-L1 levels might increase with CKD stage progression, dialysis initiation and longer dialysis duration. Further clinical investigation is required to confirm these results.

    Keywords: PD-1, PD-L1, chronic kidney diaease, Dialysis, immune checkpoint inhibitor, soluble PD-L1 (sPD-L1)

    Received: 20 Nov 2024; Accepted: 15 Jan 2025.

    Copyright: © 2025 Hayashi, Ishihara, Kawabe, Kato, Nakashima, Yamamoto, Sakano, Kobashi, Morita, Yokoo and Urashima. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mitsuyoshi Urashima, Jikei University Hospital, Minato, Japan

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