Background Renal immune-related adverse events (irAEs), are relatively rare in patients treated with immune checkpoint inhibitors (ICIs). This retrospective analysis characterizes the etiology of severe acute kidney injury (AKI) in patients treated with ICIs at the University of California, San Diego.

Methods The electronic medical record was used to identify all patients with an estimated glomerular filtration rate (eGFR) <15 mL/hr who received ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, cemiplimab between 1/2000 and 1/2019. Patients with baseline eGFR < 15 mL/hr or who experienced an eGFR decline to <15 mL/hr prior to ICI initiation were excluded. Extracted data included serum creatinine, eGFR, ICI dose, urinalysis, renal ultrasound, clinical documentation of both ICI-related nephritis and other suspected causes of AKI. These data were analyzed to determine cause of AKI and possible relation to ICI.

Results 46 patients who received ICI therapy and subsequently developed an AKI with eGFR <15 mL/hr were identified. Three of these 46 patients (6.5%) had AKIs partially or predominately attributed by the clinician to ICI therapy (table 1). Characteristics of ICI-related AKI for these patients are summarized in (table 2). AKI onset occurred 32–110 days after ICI initiation. All three patients exhibited proteinuria, pyuria, and hematuria on urinalysis with negative urine cultures, but none underwent confirmatory renal biopsy. Only one patient had urine eosinophils checked, which was negative. Two (66%) of these patients received high-dose corticosteroids with subsequent complete eGFR recovery. Neither of these two patients required renal replacement therapy. One patient (33%) declined corticosteroid treatment due to concomitant multiorgan failure. An additional four (8.7%) patients developed multifactorial AKIs with other concurrent IRAEs that were treated with corticosteroids, but were not formally diagnosed with ICI-related AKI.

Conclusions In our cohort, 6.5% of patients who develop AKI after receiving ICI therapy experienced immune-related nephritis. A further 8.7% of patients experienced other irAEs with AKI, suggesting that the true prevalence of immune-related nephritis is likely underdiagnosed. Notably, 84.8% of patients who develop AKI after ICI therapy have a non-ICI-related etiology, and no patient in our cohort of 46 patients underwent renal biopsy, highlighting the need for blood-based biomarker development for immune-related nephritis.

Ethics Approval The study was approved by the University of California San Diego’s Institutional Review Board, approval number 150348.