This study provides critical pathological evidence for the clinical diagnosis and management of irAE-related renal injury, suggesting that renal biopsy should be actively considered in complex cases to confirm the etiology of AIN and avoid unnecessary interruptions of immunotherapy or exposure to corticosteroids.
Literature Overview
The article titled 'Biopsy-Confirmed Acute Interstitial Nephritis in Patients Treated with Immune Checkpoint Inhibitors: A Single-Center Retrospective Case Series,' published in the journal Antibodies, systematically investigates the incidence, clinical characteristics, and renal outcomes of biopsy-confirmed acute interstitial nephritis (AIN) among patients receiving immune checkpoint inhibitors (ICI). By retrospectively analyzing five years of renal biopsy data from a single center, the study clarifies the real-world prevalence of ICI-AIN and highlights its nonspecific clinical presentation and high rate of severe acute kidney injury (AKI). It emphasizes the importance of differentiating drug-induced renal injury from other causes of renal dysfunction in the context of cancer immunotherapy.Background Knowledge
Currently, ICIs have become standard treatments for various advanced malignancies, enhancing anti-tumor T-cell responses by blocking the CTLA-4, PD-1, or PD-L1 pathways. However, this immune activation can also lead to immune-related adverse events (irAEs), with the kidneys being one of the affected organs. AKI is common among patients undergoing ICI therapy, but its etiology is diverse, including acute tubular injury, prerenal azotemia, and AIN. Among these, AIN is the most frequent pathological type of ICI-associated nephrotoxicity, yet there is a lack of biopsy-confirmed data, leading to diagnoses often based on clinical inference. Currently, accurately attributing renal injury to ICI in the context of irAEs remains challenging, as patients frequently use other medications such as proton pump inhibitors (PPIs) and nonsteroidal anti-inflammatory drugs (NSAIDs), which are known to cause AIN, complicating causal assessment. Additionally, the absence of specific biomarkers limits the sensitivity of non-invasive diagnosis, while although renal biopsy is the gold standard, concerns remain about its implementation. Therefore, this study aims to fill this evidence gap by systematically analyzing biopsy-confirmed AIN cases, providing a more solid pathological basis for clinical decision-making.
Research Methods and Experiments
The authors conducted a single-center, retrospective observational study at Attikon University Hospital, National and Kapodistrian University of Athens, including patients who underwent renal biopsy between February 2021 and December 2025. By searching renal pathology archives, all cases showing acute interstitial nephritis (AIN) on biopsy were identified. Further screening through tumor registries and medical record reviews selected patients with prior exposure to immune checkpoint inhibitors (ICI) before the onset of acute kidney injury (AKI), and whose renal injury was clinically attributed to ICI by the nephrology team. The study calculated the proportion of ICI-AIN among all renal biopsies and among all patients receiving ICI therapy. Data extracted included demographics, tumor types, ICI regimens, concomitant medications, laboratory parameters, pathological findings, treatments, and renal functional recovery. Renal recovery was defined as serum creatinine (SCr) returning to within 25% of baseline or <1.4 mg/dL (complete recovery), or a decrease ≥50% from peak levels but not meeting full criteria (partial recovery).
The study screened 339 renal biopsies and identified 15 cases of AIN, 12 of which were attributed to ICI exposure, accounting for 3.5% of all renal biopsies and 0.8% of the 1,472 patients treated with ICI. All patients exhibited nonspecific urinary abnormalities, including pyuria in all cases, 83.3% reaching KDIGO stage 3 AKI, negative urine cultures, and subnephrotic-range proteinuria. Pathology revealed typical interstitial inflammation, tubulitis, and interstitial edema, with some cases showing concurrent acute tubular injury. All patients received glucocorticoid treatment, and none required renal replacement therapy.Key Conclusions and Perspectives
Research Significance and Prospects
This study underscores AIN as an important differential diagnosis in AKI within the context of ICI therapy, particularly in cases of severe or persistent renal dysfunction, where renal biopsy should be actively considered. This helps prevent misdiagnosing other etiologies as ICI-related nephrotoxicity, thereby avoiding unnecessary discontinuation of ICI and ensuring continuity of anti-tumor therapy. At the same time, a confirmed AIN diagnosis supports timely initiation of immunosuppressive treatment, potentially improving renal outcomes.
From a drug development perspective, more specific biomarkers (e.g., T-cell clonal expansion, urinary cytokines) need to be explored to reduce reliance on invasive diagnostics. Additionally, the finding that some patients do not fully recover renal function suggests future research should focus on renal protective strategies or combination therapies. For clinical monitoring, it is recommended to enhance renal function surveillance during ICI therapy, especially when concomitantly using medications such as PPIs, to increase awareness of subclinical renal injury.
Conclusion
This study systematically characterizes the clinical features and outcomes of biopsy-confirmed ICI-related acute interstitial nephritis, revealing that although rare in real-world settings, it can lead to severe acute kidney injury and lacks specific urinary manifestations. Renal biopsy plays an irreplaceable role in establishing definitive diagnosis and excluding other etiologies, helping optimize the management of immune-related adverse events. The study indicates that even after corticosteroid treatment, some patients experience residual renal impairment, highlighting the importance of early recognition and intervention. From a translational medicine perspective, this work provides critical clinical data for building more precise nephrotoxicity prediction models and developing non-invasive diagnostic tools. Future research should focus on identifying high-risk populations, exploring novel biomarkers, and establishing multidisciplinary collaborative pathways to balance anti-tumor efficacy with organ protection, ultimately improving overall care for cancer patients.
