A Case of Acute Tubular Interstitial Nephritis (ATIN) with Thrombotic Microangiopathy Two Days After Immune Checkpoint Inhibitor Initiation

Introduction: Immune checkpoint inhibitor (ICI) acute kidney injury (ICI-AKI) complicated by thrombotic microangiopathy (TMA) is rare, with less than 15 documented cases in current literature, and has been associated with poorer prognosis. Time from starting ICI to ICI-AKI is usually 4 months, with fewer than 5% occurring within a week. We present a patient with severe AKI two days after starting ICI, and renal biopsy demonstrating ATIN, TMA, and ATN. Case Description: 59M with hepatocellular cancer, presented with diarrhea two days after his first course of durvalumab and tremelimumab. He was started on antibiotics for bacteremia. Urinalysis was notable for hematuria, pyuria, and proteinuria. Urine microscopy showed brown granular casts. Labs for hemolysis were equivocal. GN workup was negative. Renal function did not recover and hemodialysis (HD) was initiated. After stabilization, kidney biopsy was obtained, revealing ATI with tubulointerstitial inflammation. PDL1 staining was positive in inflammatory cells and associated tubular epithelium. Electron microscopy showed expansion of the subendothelial space with mesangial interposition. Initiation of glucocorticoids (GC) was delayed for one week due to upper GI bleed. He remained on HD despite GC and suffered a tumor rupture days later, resulting in multiorgan failure and cardiac arrest. Discussion: Onset of ICI-AKI can vary from less than a week to over a year after ICI initiation. This patient developed severe AKI only two days after starting ICI. Although septic ATN was contributory, biopsy revealed ATI and tubulointerstitial inflammation consistent with AIN. PDL1 expression in those areas is consistent with an ICI etiology. Glomerular changes were indicative of TMA. In patients with suspicion for ICI-ATIN, prompt discontinuation of the offending drug and early initiation of GC, even before biopsy, may improve chances of renal recovery. Decision to biopsy depends on clinical context. In such cases, treatment is guided by ATIN management. Although ICI-AKI is uncommon, early recognition is key to optimizing renal outcomes.