Tacrolimus as a Treatment of Immunotherapy-Induced Minimal Change Disease

Introduction: Immune-related adverse reactions affecting the kidneys are a well-recognised complication of immune-checkpoint inhibitors (ICIs). Causatively suspected with temporarily related acute kidney injuries (AKI), acute interstitial nephritis (AIN) is believed to represent the most common pathology for ICI-induced kidney injury. ESMO guidelines currently recommend consideration of a renal biopsy on a case-by-case basis. However, glomerulonephritis is an increasingly recognised manifestation of ICI-induced kidney injury. Case Description: We outline the case of a 76 year-old male who developed an AKI one week after receiving combination ipilimumab-nivolumab, with baseline creatinine of 86 umol/L which peaked at 529 umol/L. Urinalysis demonstrated 1+ protein and 3+ blood, and ICI-induced AIN was presumed. He received IV methylprednisolone 1 g x 3 doses, and weaned off steroids completely in Jan 2024 as his renal function returned back to baseline. Within 3 weeks of stopping steroids he then sustained a further AKI, with an albumin: creatinine ratio of 814 mg/mmol – 4 months after last receiving immunotherapy. After a normal ultrasound, renal biopsy confirmed minimal change disease. He was initiated on IV methylprednisolone, followed by a weaning course of prednisolone with tacrolimus 1 mg BD and switch thereafter to tacrolimus monotherapy - his renal recovery has so far been maintained with a normalised urinary ACR and creatinine. Discussion: This case highlights a case of minimal change disease which was steroid responsive and now remains in remission with a single steroid sparing agent (Tacrolimus). It has been suggested that approximately 8% of immunotherapy- induced AKI have glomerular involvement. Identifying proteinuria early is therefore of vital importance to raise diagnostic suspicion, and to aid with decisions around whether to perform a renal biopsy. Identification of minimal change disease also enables the utilisation of the steroid-sparing agent tacrolimus, which has been suggested to be non-inferior to steroids. This case demonstrates no relapse despite completion of a steroid reducing regime whilst on tacrolimus therapy at time of writing.