Renal adverse effects of immune checkpoints inhibitors in clinical practice: ImmuNoTox study

Background/objectives: Acute Kidney Injury (AKI), induced by Checkpoint Inhibitors therapies (CPI-induced AKI), is an uncommon but severe Immune-Related Adverse Event (IRAE). The aim was to describe the epidemiology, risks factors, clinical, and laboratory characteristics of these renal adverse events (AEs) in a real-life cohort treatment.

Design/participants: Consecutive patients undergoing a checkpoint inhibitor (CPI) therapy at the Hôpital Lyon Sud from January 2015 to July 2017 were included. A systematic retrospective analysis of medical files was performed, monthly serum creatinine levels, associated treatments, and occurrence of other IRAEs data were collected. AKI episodes explained by classic AKI aetiologies (prerenal, obstructive, septic) were excluded from the analysis.

Results: CPI-induced AKI incidence was 3.7% (13/352) and appeared to be time-dependent (7.7% (11/143) for patients with >3 months of CPI exposure), ranging from 1 to 16 months. All cases with available histology were acute tubulointerstitial nephritis (ATIN), with poor urinary sediment. The severity of AKI was mild (stage 1 in 50% of cases), with no need for renal-replacement therapy. Although CPI-induced AKI patients had more frequently other IRAEs (77% versus 39%), this was not associated with a greater risk of AKI. Pre-existing chronic kidney disease (defined as an estimated glomerular filtration rate (eGFR) <60 ml/min) was not associated with a greater risk of CPI-induced AKI. Treatments of CPI-induced AKI were heterogeneous, with discontinuation of CPIs, and inconstant systemic corticosteroid therapy.

Conclusion: The monitoring of renal function and early identification of AKI during CPIs treatment is essential. The optimal management of CPI-induced AKI remains unclear and requires a close collaboration between the oncology and nephrology departments.

Clinical relevancy statement: Immune checkpoint inhibitors (CPIs) have dramatically improved patient outcomes in different malignant contexts such as melanoma, non-small cell lung cancers (NSCLC) and urologic cancers. Usually well-tolerated, CPIs are however associated with immune-related adverse events (IRAEs). Among them, acute kidney injury (AKI) is uncommon, and not well-described. Following the exponential increase in the prescription of CPIs, previously uncommon cases of IRAEs (such as AKI) have become common occurrence in referral centres. Data regarding the epidemiology, risk factors, or management of CPI-induced AKI are currently lacking or can be discordant. Data regarding CPI-induced AKI, in a large real-life cohort were reported herein.