Acute Interstitial Nephritis and Renal Tubular Acidosis Associated with Bispecific Anti-T Cell Immunoreceptor with Ig and ITIM Domains (TIGIT)/Anti-Programmed Cell Death Protein 1 (PD-1) Therapy

Introduction: Immune checkpoint inhibitors (ICIs) are increasingly used in oncology, but their association with immune-related adverse events (irAEs), including acute interstitial nephritis (AIN), is well-established. Renal tubular acidosis (RTA), particularly in the absence of classic acute kidney injury (AKI) features, remains underrecognized. Here, we present a case of RTA and AIN associated with a novel bispecific Anti-TIGIT/Anti-PD-1 antibody. Case Description: An 80-year-old female with metastatic lung adenocarcinoma (PD-L1 expression 60%) was initiated on a novel bispecific Anti[1]TIGIT/Anti-PD-1 antibody. After approximately six months of therapy, she presented to the emergency department with nausea, vomiting, abdominal pain, and unintentional weight loss. Initial labs showed AKI with serum creatinine (sCr) of 2.27 mg/dL (baseline 0.79 mg/dL) and non-anion gap metabolic acidosis (serum bicarbonate 11 mmol/L). These findings were attributed to presumed volume depletion and gastrointestinal losses. She was treated with intravenous bicarbonate, with improvement in sCr to 1.0 mg/dL and bicarbonate to 29 mmol/L. However, at outpatient nephrology follow-up, she was found to have recurrent AKI (sCr 1.4 mg/dL) and metabolic acidosis (bicarbonate 14 mmol/L) attributed to a distal RTA. She was started on oral sodium citrate/potassium citrate (Bicitra), but the acidosis persisted, prompting a kidney biopsy. Histopathologic examination revealed acute interstitial nephritis. She was started on a 4-week prednisone taper. At follow-up, her renal function and acid-base status normalized (sCr 0.8 mg/dL, bicarbonate 24 mmol/L). Discussion: This case illustrates a delayed-onset renal irAE characterized by both distal RTA and AIN in the setting of investigational dual immune checkpoint blockade. The biphasic clinical course underscores the importance of continued monitoring even after apparent recovery from initial AKI. Clinicians should maintain high suspicion for immune-mediated nephrotoxicity in patients on ICIs presenting with unexplained acidosis or recurrent kidney dysfunction. Early recognition and biopsy-guided immunosuppressive therapy may facilitate full renal recovery.