Immune-related acute kidney injury in Australian non-small cell lung cancer patients: Real-world results

Andrea Knox; Thomas Cloney; Hannah Janssen; Benjamin J Solomon; Marliese Alexander; Irene Ruderman; Thomas John

doi:10.1016/j.lungcan.2023.107325

Immune-related acute kidney injury in Australian non-small cell lung cancer patients: Real-world results

Lung Cancer. 2023 Oct:184:107325. doi: 10.1016/j.lungcan.2023.107325. Epub 2023 Aug 9.

Authors

Andrea Knox¹, Thomas Cloney², Hannah Janssen², Benjamin J Solomon³, Marliese Alexander⁴, Irene Ruderman⁵, Thomas John⁶

Affiliations

¹ Department of Medical Oncology, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia. Electronic address: a.knox@alfred.org.au.
² Department of Medical Oncology, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia.
³ Department of Medical Oncology, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.
⁴ Pharmacy Department, Peter MacCallum Cancer Centre, 305 Grattan St, Parkville, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.
⁵ The Royal Melbourne Hospital, 300 Grattan Street, Parkville, Australia.
⁶ Department of Medical Oncology, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia; The Royal Melbourne Hospital, 300 Grattan Street, Parkville, Australia.

PMID: 37573702
DOI: 10.1016/j.lungcan.2023.107325

Abstract

Background: The use of immune checkpoint inhibitors has altered therapeutic paradigms in NSCLC. However, they may cause immune-related toxicities, including acute kidney injury (irAKI), especially when combined with nephrotoxic agents. We investigated the incidence, management and outcomes of AKI in Australian NSCLC patients.

Methods: Medical records from a cancer centre registry were reviewed. AKI was defined and graded on absolute creatinine rise, or rise above baseline. Fishers exact test compared proportions. The Kaplan-Meier method estimated survival, and multiple logistic regression tested for risk factors.

Results: Of 449 patients who underwent immunotherapy from 2013 to 2021, the median age was 65 years and 61% were male. Metastatic disease was present in 68% at diagnosis, the remainder had stage Ia-III disease; 70% had adenocarcinoma; and 17% had EGFR mutations. AKI was identified in 65 patients (14.5%) of which 19 were irAKI (4.2%). Within irAKI patients, eleven (58%) had other immune-related adverse events. Median time to irAKI onset was 4 months (IQR 4-6). Seventeen (89%) patients had AKI stage 1 or 2; two had stage 3. Eleven patients developed chronic kidney disease; none required renal replacement therapy. Kidney biopsies demonstrated acute interstitial nephritis (n = 3), acute tubular necrosis (n = 1) and anti-phospholipase A2 receptor negative membranous glomerulonephritis (n = 1). Five patients were rechallenged with immunotherapy; two had recurrent irAKI. The median overall survival for those with irAKI was not reached versus 12 months with no irAKI (HR 0.35, 95 %CI 0.20-0.60, p = 0.01). Risk factors for irAKI included having an additional, non-renal irAE (OR 6.21, 95 %CI 2.35-17.26, p ≤ 0.01); immunotherapy combined with other cancer therapies (OR 5.62, 95 %CI 2.08-16.20, p ≤ 0.01); and ECOG performance status > 1 (OR 4.39 (95 %CI 1.11-14.90, p = 0.02) CONCLUSIONS: The incidence of irAKI was similar to the published literature. Renal recovery was poor, however survival was not compromised. Improved diagnostic and therapeutic strategies for irAKI would benefit this population.

Keywords: Acute kidney injury; Adverse event; Immune checkpoint inhibitor; Non-small cell lung cancer (NSCLC).

MeSH terms

Acute Kidney Injury* / epidemiology
Acute Kidney Injury* / etiology
Aged
Australia / epidemiology
Carcinoma, Non-Small-Cell Lung* / drug therapy
Female
Humans
Lung Neoplasms* / drug therapy
Male
Retrospective Studies