Biomarkers, Clinical Features, and Rechallenge for Immune Checkpoint Inhibitor Renal Immune-Related Adverse Events

Abstract

Introduction Immune checkpoint inhibitors (ICIs) are effective in treating several cancers; however, acute kidney injury (AKI) can occur as part as an immune-related adverse event (iRAE). Biomarkers at the time of AKI diagnosis may help determine whether they are ICI- related and guide therapeutic strategies. Methods In this retrospective study, we reviewed patients with cancer treated with ICI therapy between 2014 and 2020 who developed AKI (defined as a ≥1.5-fold increase in serum creatinine [SCr]) that was attributed to ICI (ICI-AKI) and compared them with an adjudicated non–ICI-AKI group. Clinical and laboratory features, including SCr, serum C-reactive protein (CRP), and urine retinol binding protein/urine creatinine (uRBP/Cr) levels at AKI event were evaluated. Results There were 37 patients with ICI-AKI and 13 non–ICI-AKI referents in the cohort for analysis. At time of AKI, SCr, CRP, and uRBP/Cr were significantly higher in the ICI-AKI compared with the non–ICI-AKI patients (median [interquartile range (IQR)] SCr 2.0 [1.7, 2.9] vs. 1.5 [1.3, 1.6] mg/dl, serum CRP 54.0 [33.7, 90.0] vs. 3.5 [3.0, 7.9] mg/l, and uRBP/Cr 1927 [1174, 46,522] vs. 233 [127, 989] μg/g Cr, respectively, P < 0.05 for all). Compared with the referent group, time from ICI initiation to AKI was shorter in the ICI-AKI patients. Among the ICI-AKI group, complete renal recovery occurred in 39% of patients by 3 months; rechallenge occurred in 16 (43%) of patients, of whom 3 (19%) had recurrence of AKI. Conclusion Our findings suggest that serum CRP and uRBP/Cr may help to differentiate AKI due to ICI from other causes.

Is Rechallenge Appropriate in Patients that Develop Immune Checkpoint Inhibitor-Associated AKI?: PRO

“…As use of AINinducible drugs, such as proton pump inhibitors (PPIs) and non-steroidal anti-inflammatory drugs (NSAIDs) have been implicated in increased risk to develop ICI-AKI, 5 we looked at AIN drug subtype at rechallenge and no significant difference was found in patients with recurrent AKI and those without a recurrent AKI as well as no difference in the dose of corticosteroids. 6 The above study findings were corroborated in a larger multicentre retrospective study by Cortazar et al In this multicenter study with a total of 138 patients with ICI-AKI, 31 (22%) patients were rechallenged approximately 1.8 months after the diagnosis of ICI-AKI.…”

“…Importantly, Isik et al did not find survival differences between patients rechallenged versus those not rechallenged with ICI therapy. 6 An explanation for these results could be related to potential bias towards treating patients with more aggressive malignancies with ICI again due to lack of an alternative treatment with other conventional therapies and potentially decreasing survival benefit.…”

Immune Checkpoint Inhibitors and Kidney Toxicity: Advances in Diagnosis and Management

“…On the contrary, when both biomarkers are within normal limits, the likelihood of a ICI-induced AKI is very low. 13 In another study in lung cancer patients, neutrophil to lymphocyte and platelet to lymphocyte ratios were predictive of immune related adverse events. 48 Current research focusing on J o u r n a l P r e -p r o o f immunological markers specific to ICI-induced immune dysregulation, such as T-cell repertoire and profiling of gene expression may provide sophisticated ways to analyze and detect ICI-AIN and other immune related adverse events.…”

The Challenges of Acute Interstitial Nephritis: Time to Standardize

“…Importantly, new insights into the pathogenesis of AIN as well its diagnosis and therapy may be garnered from this study. A recent study measured urinary retinol-binding protein/Cr in patients with immune-checkpoint inhibitor(ICPI)-associated AKI(14/37 had biopsy-proven AIN) and 13 patients with non-ICPI-associated AKI(2/4 with biopsy-proven acute tubular injury) 22 . In a subgroup of patients, urinary retinol-binding protein/Cr was statistically increased in the ICPI-AKI group vs. the ICPI-non-AIN group.…”