The differentiation and intervention strategies for acute kidney injury after or induced by immune checkpoint inhibitors

Abstract

With the increasing popularity of immune checkpoint inhibitors (ICIs) in tumor treatment, the incidence of immune-related adverse events (irAEs), including acute kidney injury (AKI), is on the rise. Renal biopsy serves as the gold standard for determining the true etiology of AKI following ICIs administration; however, due to potential risks and associated losses with this procedure, comprehensive analysis of physiological data and predictive models are gradually being incorporated into clinical practice to differentiate AKI etiologies. These include criteria such as a ≥ 100% increase in serum creatinine (Scr) from baseline or a 50% increase accompanied by other pathological manifestations, renal replacement therapy (RRT), or absence of any other reasonable cause. Currently, cessation of ICIs and steroid therapy represent commonly employed treatment approaches; nevertheless, these strategies have inherent side effects and may not be feasible for certain patient populations, such as those with diabetes, posing challenges for clinicians. Recent studies have demonstrated that rituximab, mycophenolate mofetil (MMF), and infliximab can potentially replace steroid therapy in managing ICIs-induced AKI (ICIs-AKI), offering a novel therapeutic perspective. This review provides an overview of non-invasive methods for distinguishing between AKI following ICIs use and ICIs-AKI while discussing strategies for treating ICIs-AKI.

Keywords: Immune checkpoint inhibitors; acute kidney injury; differentiation; treatment.

Figure 1

Baseline characteristics of the aAKI and ICIs-AKI. The other types in (A) in ascending order are: glioblastoma multiforme, liquid, colorectum, head and neck, gastroduodenum, breast, hepatobiliary, urinary tract. The other types in (B) in ascending order are: pancreatic, Hodgkin’s lymphoma, colorectum, gastrointestinal tract, renal, hepatobiliary. The other types in (C) in ascending order are: congestive hearts failure, chronic obstructive pulmonary disease, autoimmune disease, cerebrovascular disease, coronary heart disease, liver disease, chronic kidney disease, anemia. The other types in (D) in ascending order are: cerebrovascular disease, peripheral vascular disease, coronary heart disease, heart failure, liver disease, chronic obstructive pulmonary disease, chronic kidney disease. The other types in (E) in ascending order are: Allopurinol, steroid, H2 blockers, diuretics, ACEi/ARBs. The other types in (F) in ascending order are: H2 antagonist, ACEi/ARBs, corticosteroids, antibiotics, Fluindione, calcium channel blocker, diuretics, NSAIDs. The types in (G) in ascending order are: anti-PD-L1, anti-CTLA-4, anti-PD-1. The types in (H) in ascending order are: anti-PD-L1, anti-CTLA-4, anti-PD-1. Abbreviations: aAKI, all-cause acute kidney injury that occurs after using immune checkpoint inhibitors; ACEIs, angiotensin converting enzyme inhibitors; ARBs, angiotensin receptor blockers; CTLA-4, cytotoxic T lymphocyte antigen-4; ICIs-AKI, acute kidney injury induced by immune checkpoint inhibitors; NSAIDs, nonsteroidal anti-inflammatory drugs; PD-1, programmed cell death 1; PD-L1, programmed cell death ligand; PPIs, proton pump inhibitors.

Figure 2

Risk factors of aAKI and ICIs-AKI. Abbreviations: aAKI, all-cause acute kidney injury that occurs after using immune checkpoint inhibitors; ACEIs, angiotensin converting enzyme inhibitors; Alb, albumin; ARBs, angiotensin receptor blockers; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; ICIs-AKI, acute kidney injury induced by immune checkpoints inhibitors; irAEs, immune related adverse events; NSAIDs, nonsteroidal anti-inflammatory drugs; PD-1, programmed cell death 1; PPIs, proton pump inhibitors.

Figure 3

By Figdraw. Mechanisms of ICIs-AKI. A: T cells recognize self-antigens and stimulate B cells to produce antibodies that target tissues; B: The protection pathways of PD-L1 and PD1 are blocked; C: ICIs induce T cells to produce inflammatory factors and break tissues; D: T cells previously exposed to nephrotoxic drugs were reactivated by ICIs; E: The binding of ICIs to kidney tissue results in the formation of antigens. Abbreviations: aAKI, all-cause acute kidney injury that occurs after using immune checkpoint inhibitors; ACEIs, angiotensin converting enzyme inhibitors; Alb, albumin; ARBs, angiotensin receptor blockers; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; ICIs-AKI, acute kidney induced by immune checkpoints inhibitors; irAEs, immune related adverse events; NSAIDs, nonsteroidal anti-inflammatory drugs; PD-1, programmed cell death 1; PPIs, proton pump inhibitors.