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

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.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.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.