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. 2025 Aug 26:13:e19886.
doi: 10.7717/peerj.19886. eCollection 2025.

A closer look at severe acute kidney injury: risk factors and outcomes in PD-1/PD-L1 antibody treatment from a retrospective study

Yuemeng Wu  1   2 , Lingfan Luo  2   3 , Xin Sun  4 , Xiaolan Ye  5 , Yan Ren  2 , Wei Zhang  2 , Shuangshan Bu  1 , Yiwen Li  2 , Bin Zhu  2 , Lina Shao  2   3
Affiliations

A closer look at severe acute kidney injury: risk factors and outcomes in PD-1/PD-L1 antibody treatment from a retrospective study

Yuemeng Wu et al. PeerJ. .

Abstract

Background: Immune checkpoint inhibitors (ICIs) have improved cancer survival but increase the risk of adverse events, including acute kidney injury (AKI). Severe AKI, though rare, can disrupt treatment and worsen outcomes. Yet, research on risk factors for severe AKI in patients on PD-1/PD-L1 therapies is limited. This study aimed to identify these risk factors.

Methods: This retrospective cohort study analyzed electronic medical records from Zhejiang Provincial People's Hospital from January 2019 to July 2023. In total, 907 patients who met the inclusion criteria, with a median age of 64 years, were included in the analysis. Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analyses were conducted to determine independent risk factors for severe AKI.

Results: Severe AKI was observed in 3.2% of patients with AKI, with a significantly higher mortality rate than in non-AKI patients (20.7% vs. 4.1%) during the follow-up period. Multivariate Cox regression analysis identified elevated gamma-glutamyl transferase (hazard ratio (HR): 1.17), diuretic use (HR: 3.61), nonsteroidal anti-inflammatory drug (NSAID) use (HR: 4.58), and cytotoxic drugs (HR: 5.04) as independent risk factors for severe AKI. Only 11 patients (37.5%) with severe AKI recovered.

Conclusions: This study highlights the importance of monitoring these factors to reduce the risk of severe AKI in patients receiving PD-1/PD-L1 antibody therapy.

Keywords: Immune checkpoint inhibitors; Oncology; Risk factors; Severe acute kidney injury.

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Conflict of interest statement

The authors declare there are no competing interests.

Figures

Figure 1
Figure 1. Flow diagram of the study design.
PD-1, programmed death-1; PD-L1, programmed death ligand-1; AKI, acute kidney injury; ZJPH, Zhejiang Provincial People’s Hospital; Scr, serum creatinine; eGFR, estimated Glomerular Filtration Rate.
Figure 2
Figure 2. Kaplan–Meier survival analysis showed that patients with severe AKI had a lower survival and poorer prognosis than those in the non-AKI group.
Figure 3
Figure 3. Multivariate COX regression analysis of independent risk factors associated with severe AKI.
GGT, gamma-glutamyl transpeptidase; ALB, albumin; Hb, hemoglobin; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; NSAIDs, nonsteroidal anti -inflammatory drug.
Figure 4
Figure 4. The dynamic alterations of concordance index.
Figure 5
Figure 5. Relationship between the four variables and severe AKI incidence.
(A) Severe AKI incidence according to GGT (p < 0.0001); (B) Severe AKI incidence according to diuretic medicine (p < 0.0001); (C) Severe AKI incidence according to NSAIDs (p < 0.001); (D) Severe AKI incidence according to cytotoxic drugs (p < 0.0001).
Figure 6
Figure 6. Recovery of renal function of patients with severe AKI.
Of the 29 patients with severe AKI, two fully recovered, nine partially recovered, 13 did not recover, and five were lost to follow-up. Among the 23 stage 2 AKI patients, two fully recovered, seven partially recovered, 10 did not recover, and four were lost to follow-up. Of the six stage 3 AKI patients, two partially recovered, three did not recover, and one was lost to follow-up.
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References

    1. Bagshaw SM, Langenberg C, Haase M, Wan L, May CN, Bellomo R. Urinary biomarkers in septic acute kidney injury. Intensive Care Medicine. 2007;33(7):1285–1296. doi: 10.1007/s00134-007-0656-5. - DOI - PubMed
    1. Barbir EB, Kitchlu A, Herrmann SM. Immune checkpoint inhibitor-associated nephritis-treatment standard. Nephrology Dialysis Transplantation. 2024;39(11):1785–1798. doi: 10.1093/ndt/gfae184. - DOI - PubMed
    1. Carlisle ML, King MR, Karp DR. Gamma-glutamyl transpeptidase activity alters the T cell response to oxidative stress and Fas-induced apoptosis. International Immunology. 2003;15(1):17–27. doi: 10.1093/intimm/dxg010. - DOI - PubMed
    1. Cortazar FB, Kibbelaar ZA, Glezerman IG, Abudayyeh A, Mamlouk O, Motwani SS, Murakami N, Herrmann SM, Manohar S, Shirali AC, Kitchlu A, Shirazian S, Assal A, Vijayan A, Renaghan AD, Ortiz-Melo DI, Rangarajan S, Malik AB, Hogan JJ, Dinh AR, Shin DS, Marrone KA, Mithani Z, Johnson DB, Hosseini A, Uprety D, Sharma S, Gupta S, Reynolds KL, Sise ME, Leaf DE. Clinical features and outcomes of immune checkpoint inhibitor-associated AKI: a multicenter study. Journal of the American Society of Nephrology. 2020;31(2):435–446. doi: 10.1681/ASN.2019070676. - DOI - PMC - PubMed
    1. Cutrín JC, Zingaro B, Camandola S, Boveris A, Pompella A, Poli G. Contribution of gamma glutamyl transpeptidase to oxidative damage of ischemic rat kidney. Kidney International. 2000;57(2):526–533. doi: 10.1046/j.1523-1755.2000.00871.x. - DOI - PubMed

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