Immune Checkpoint Inhibitors and Immune-Related Adverse Renal Events

Abstract

Renal toxicities have been increasingly recognized as complications of the immune checkpoint inhibitors (ICIs). Recent studies have outlined the incidence and potential risk factors for nephrotoxicity. For clinicians, the key question is how to manage patients who develop these adverse renal effects. This is of paramount importance to providers as ICI use for cancer therapy becomes more widespread and nephrotoxicity increasingly develops. As clinicians encounter ICI-associated nephrotoxicity, an appropriate approach to management is required to facilitate the best outcomes in patients with cancer. Importantly, ICI rechallenge in patients who developed ICI-related acute kidney injury (AKI) is unclear and represents a conundrum for providers. Clinicians struggle with the “if, when, and how to” questions related to ICI rechallenge in this subset of patients. In addition, ICI use in the transplant population raises concerns for promoting acute rejection when treating cancer in these patients. We herein review current information on these various topics.

Immune evasion in renal cell carcinoma: biology, clinical translation, future directions

“…These autoimmune side effects have a wide range of manifestations, are currently largely unpredictable, and depend on the organ affected by the autoimmunity 83 . Although a less common checkpoint inhibitor-induced side effect than autoimmune pneumonitis/ colitis/ thyroiditis, autoimmune nephritis is well described and seen in a small J o u r n a l P r e -p r o o f minority of patients that receive immune checkpoint inhibitors 84,85 . It is interesting to note that the predominant pathology of checkpoint inhibitor-induced autoimmune nephritis is tubulointerstitial nephritis, although membranous glomerulonephritis, IgA nephropathy, minimal change disease, and focal necrotizing glomerulonephritis have also been reported 84 .…”

Variable Expression of Programmed Cell Death Protein 1-Ligand 1 in Kidneys Independent of Immune Checkpoint Inhibition

“…Acute interstitial nephritis (AIN) is a potential and deleterious irAE in the kidney observed in patients receiving ICIs and is the most common biopsy-proven diagnosis in patients developing acute kidney injury (AKI) ( 3 ). AIN in patients receiving ICIs is associated with tubular positivity for PD-L1, suggesting that PD-L1 positivity reflects susceptibility to develop renal complications with these agents ( 3 , 4 ). Additionally to AIN, there is increasing recognition that glomerular disease and renal vasculitis are associated with ICI-related kidney injury with reports describing both, nephrotic and nephritic clinical presentations ( 5 , 6 ).…”

Fatal Adverse Events Associated With Immune Checkpoint Inhibitors in Non–small Cell Lung Cancer: A Systematic Review and Meta-Analysis

“…However, with the increased application of ICI drugs in NSCLC, the number of reports about toxicity has also increased, which warrants further research, particularly with regard to treatment-related fatal adverse events (FAEs) ( 12 , 13 ). Of note, most previous studies focused on the overall incidence of adverse events among all applicable cancers or considered the specific incidence of a certain system ( 14 – 17 ). There are scarce reports focused on FAEs, and further investigations are needed.…”