Everolimus-Induced Acute on Chronic Tubulointerstitial Nephritis (TIN) in a Patient with a Neuroendocrine Tumor

Introduction: Nephrotoxicity from mTOR inhibitors has been associated with renal microangiopathy TMA. We report a case of acute renal injury (AKI) associated with everolimus acute on chronic TIN. Case Description: 56 years old female with neuroendocrine tumor of the small intestine treated with everolimus was admitted for AKI with a creatinine of 5.3 with a baseline of 0.8 mg/dL 1 month prior to admission. UA showed 30 mg% protein, moderate blood, trace leukocyte esterase, WBCs 0-5, RBCs 3-5, 0-2 granular cast per HPF, elevated everolimus level of 17.6 ng/ml, LDH 1644 U/L, low haptoglobin < 8 mg/dl, no schistocytes, ADAMST13 40%, negative GN serologic work up. Decline in renal function to Cr 7.3mg/dL led to hemodialysis initiation and renal biopsy. Renal biopsy showed diffuse TIN with no evidence of TMA. After drug discontinuation patient was treated with Prednisone 60 mg daily with tapering schedule over 4 weeks with improvement of Cr to 1.1mg/dL and discontinuation of dialysis. Discussion: Everolimus and other mTOR inhibitors has been associated with nephrotoxicity manifested as proteinuria and acute or chronic renal dysfunction. Pathologic damage due to TMA associated with VEGF inhibition, FSGS and tubular vacuolization has been described. We describe a rare case of acute on chronic TIN associated with everolimus that responded to drug discontinuation and steroids. She was not treated prior with immunotherapy for her malignancy and was not taking any other drugs associated with TIN. Although mTOR associated TIN is rare, a renal biopsy may be required to differentiate from TMA and ATN for appropriate management.Hematoxylin and eosin stain shows moderate mixed interstitial inflammation involving both intact and scarred areas