Clinically significant estimated glomerular filtration rate decline is common in patients receiving immune checkpoint inhibitors: implications for long-term cancer survivors

Purpose Immune checkpoint inhibitors (ICIs) are now indicated in more than one in three cancer patients. Acute kidney injury has emerged as an important complication of ICIs; however, there are no studies characterizing the long-term effects of ICIs on kidney function. Methods Retrospective cohort study of consecutive adult cancer patients treated with ICIs between 2010–2018 at two major cancer centers. The primary aim was to determine the composite outcome of incident or progressive CKD, defined as estimated glomerular filtration rate (eGFR) 90 days among patients surviving ≥1 year. The secondary objective was to determine the proportion of patients experiencing rapid eGFR decline defined as >3mL/min/1.73m 2 per year decline. Results A total of 5004 adult patients with cancer (mean [SD] age, 64 [13] years; 2699 [54%] male; 4529 [91%] White non-Hispanic) were included, and 2563 surviving ≥1 year were analyzed. During a median follow-up of 688 days (interquartile range, 496 to 1031), the overall event rate of the primary composite outcome was 17% and 20% at 3 and 5 years, respectively. Fine-Gray subdistribution multivariable hazard mode demonstrated that age and coronary artery disease were each independently associated with the primary outcome, adjusted HR (95% CI) 1.12 (1.06, 1.19) per 5 years and 1.27 (1.00-1.62), p < 0.001 and p=0.49, respectively. Conclusion New onset CKD or 30% eGFR decline is common in patients receiving ICIs who survive ≥1 year. As ICIs are increasingly used in earlier stage cancers, the impact of long term kidney function decline among survivors is extremely important. Additional studies are needed to determine the risk factors and potential modifiers for eGFR decline among patients receiving ICIs.