. 2021 May; 14(5):1301-1306.
doi: 10.1093/ckj/sfab052.

Checkpoint inhibitor therapy-associated acute kidney injury: time to move on to evidence-based recommendations

Mark A Perazella 1 Ben Sprangers 2 
  • PMID: 33970161
  •     22 References
  •     1 citations


Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment since their introduction ∼15 years ago. However, these monoclonal antibodies are associated with immune-related adverse events that can also affect the kidney, resulting in acute kidney injury (AKI), which is most commonly due to acute tubulointerstitial nephritis (ATIN). Limited data are available on the true occurrence of ICI-associated AKI. Furthermore, evidence to guide the optimal management of ICI-associated AKI in clinical practice is lacking. In this issue, Oleas et al. report a single-center study of patients with nonhematologic malignancies who received ICI treatment during a 14-month period, experienced AKI and underwent a kidney biopsy at the Vall d'Hebron University Hospital. Importantly, they demonstrate that only a minority of ICI-associated AKI patients was referred to the nephrology service and kidney biopsy was only performed in 6.4% of patients. Although the authors add to our knowledge about ICI-associated AKI, their article also highlights the need for the development of noninvasive diagnostic markers for ICI-associated ATIN, the establishment of treatment protocols for ICI-associated ATIN and recommendations for optimal ICI rechallenge in patients with previous ICI-associated AKI.

Keywords: acute kidney injury; acute tubulointerstitial nephritis; immune checkpoint inhibitors; immune-related adverse events.

Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study.
Akbar K Waljee, Mary A M Rogers, +5 authors, Brahmajee K Nallamothu.
BMJ, 2017 Apr 14; 357. PMID: 28404617    Free PMC article.
Highly Cited.
Pooled Analysis Safety Profile of Nivolumab and Ipilimumab Combination Therapy in Patients With Advanced Melanoma.
Mario Sznol, Pier Francesco Ferrucci, +19 authors, Jedd D Wolchok.
J Clin Oncol, 2017 Sep 16; 35(34). PMID: 28915085
Highly Cited.
Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes.
Alejandro Meraz-Muñoz, Eitan Amir, +6 authors, Abhijat Kitchlu.
J Immunother Cancer, 2020 Jul 01; 8(1). PMID: 32601079    Free PMC article.
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review.
Rimda Wanchoo, Sabine Karam, +6 authors, Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors.
Am J Nephrol, 2017 Jan 12; 45(2). PMID: 28076863
Highly Cited. Review.
Management of Immunotherapy-Related Toxicities, Version 1.2019.
John A Thompson, Bryan J Schneider, +28 authors, Jillian L Scavone.
J Natl Compr Canc Netw, 2019 Mar 14; 17(3). PMID: 30865922
Highly Cited.
Influence of immunoglobulin isotype on therapeutic antibody function.
Stephen A Beers, Martin J Glennie, Ann L White.
Blood, 2016 Jan 15; 127(9). PMID: 26764357    Free PMC article.
Biomarkers, Clinical Features, and Rechallenge for Immune Checkpoint Inhibitor Renal Immune-Related Adverse Events.
Busra Isik, Mariam P Alexander, +7 authors, Sandra M Herrmann.
Kidney Int Rep, 2021 Apr 30; 6(4). PMID: 33912752    Free PMC article.
Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.
Frank B Cortazar, Zoe A Kibbelaar, +28 authors, David E Leaf.
J Am Soc Nephrol, 2020 Jan 04; 31(2). PMID: 31896554    Free PMC article.
Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: A systematic analysis of the literature.
Rathi N Pillai, Madhusmita Behera, +6 authors, Suresh S Ramalingam.
Cancer, 2017 Sep 30; 124(2). PMID: 28960263    Free PMC article.
Highly Cited. Systematic Review.
Incidence and Clinical Features of Immune-Related Acute Kidney Injury in Patients Receiving Programmed Cell Death Ligand-1 Inhibitors.
Harish Seethapathy, Sophia Zhao, +14 authors, Meghan E Sise.
Kidney Int Rep, 2020 Oct 27; 5(10). PMID: 33102962    Free PMC article.
Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination.
Celine Boutros, Ahmad Tarhini, +14 authors, Caroline Robert.
Nat Rev Clin Oncol, 2016 May 05; 13(8). PMID: 27141885
Highly Cited. Review.
Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline.
Julie R Brahmer, Christina Lacchetti, +27 authors, National Comprehensive Cancer Network.
J Clin Oncol, 2018 Feb 15; 36(17). PMID: 29442540    Free PMC article.
Highly Cited.
Incidence and Prediction of Immune Checkpoint Inhibitor-related Nephrotoxicity.
Jonathan D Sorah, Tracy L Rose, +2 authors, Matthew I Milowsky.
J Immunother, 2020 Sep 15; 44(3). PMID: 32925564    Free PMC article.
The Incidence, Causes, and Risk Factors of Acute Kidney Injury in Patients Receiving Immune Checkpoint Inhibitors.
Harish Seethapathy, Sophia Zhao, +10 authors, Meghan E Sise.
Clin J Am Soc Nephrol, 2019 Nov 02; 14(12). PMID: 31672794    Free PMC article.
Highly Cited.
AKI in Patients Receiving Immune Checkpoint Inhibitors.
Mark A Perazella, Ben Sprangers.
Clin J Am Soc Nephrol, 2019 May 03; 14(7). PMID: 31048326    Free PMC article.
Acute kidney injury in patients treated with anti-programmed death receptor-1 for advanced melanoma: a real-life study in a single-centre cohort.
Claire Stein, Stéphane Burtey, +8 authors, Noémie Jourde-Chiche.
Nephrol Dial Transplant, 2020 Sep 18; 36(9). PMID: 32941608
Safety of immune checkpoint inhibitor rechallenge after discontinuation for grade ≥2 immune-related adverse events in patients with cancer.
Marion Allouchery, Thomas Lombard, +8 authors, French Network of Regional Pharmacovigilance Centers.
J Immunother Cancer, 2021 Jan 12; 8(2). PMID: 33428586    Free PMC article.
Adverse Events Associated with Immune Checkpoint Blockade.
Kenar D Jhaveri, Mark A Perazella.
N Engl J Med, 2018 Mar 23; 378(12). PMID: 29565518
Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors.
Frank B Cortazar, Kristen A Marrone, +15 authors, David E Leaf.
Kidney Int, 2016 Jun 11; 90(3). PMID: 27282937    Free PMC article.
Highly Cited.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
Urine TNF-α and IL-9 for clinical diagnosis of acute interstitial nephritis.
Dennis G Moledina, F Perry Wilson, +10 authors, Chirag R Parikh.
JCI Insight, 2019 May 17; 4(10). PMID: 31092735    Free PMC article.
Tumour- and class-specific patterns of immune-related adverse events of immune checkpoint inhibitors: a systematic review.
L Khoja, D Day, +2 authors, A R Hansen.
Ann Oncol, 2017 Sep 26; 28(10). PMID: 28945858
Highly Cited. Systematic Review.
Safety of Immune Checkpoint Inhibitor Resumption after Interruption for Immune-Related Adverse Events, a Narrative Review.
Marion Allouchery, Clément Beuvon, +3 authors, Mickaël Martin.
Cancers (Basel), 2022 Feb 26; 14(4). PMID: 35205703    Free PMC article.