#6612 acute kidney injury associated with immune checkpoint inhibitor therapy: report of 4 cases

Abstract Background and Aims Immunotherapy using immune check point inhibitors (ICIs) is the cornerstone of modern cancer therapy. Despite significant clinical benefits, ICIs are associated with remarkable adverse events of autoimmune nature involving various organs. Acute Kidney Injury (AKI) occurs more rarely, mainly with the appearance of acute interstitial nephritis. We present a series of patients with AKI after administration of immunotherapy with ICIs. Method Patient 1 with metastatic small cell lung cancer on immunotherapy with atezolizumab presented with purpura on the trunk and lower extremities, AKI, microscopic glomerular hematuria, and proteinuria. Patient 2 with esophageal malignancy on immunotherapy with pembrolizumab and worsening renal function. Patient 3 with endometrial malignancy on immunotherapy with pembrolizumab developed AKI, nephrotic syndrome and microscopic hematuria. Patient 4 with melanoma on immunotherapy with pembrolizumab presented with microscopic hematuria and rash. Results A kidney biopsy was performed in all 4 patients unreavealling the following; Patient 1: pauci-immune necrotizing glomerulonephritis with fibrinoid necrosis and inflammation in the wall of a vessel. Patient 2: acute interstitial nephritis with intense inflammation. Patient 3: findings consistent with focal segmental glomerulosclerosis (FSGS, NOS), without evidence of immune complex disease. Patient 4: focal segmental glomerulosclerosis, moderate interstitial fibrosis and interstitial nephritis in remission. The patient had already been treated with glucocorticoid. In all 4 patients immunotherapy was temporarily discontinued and they were treated with intravenous pulses of methyl-prednisolone followed by oral glucocorticoids, with significant improvement of kidney function and resolution of all extra renal manifestation i.e skin rash etc. Escalation of immunosuppressive therapy with the addition of another agent was avoided in order not to cause relapse of the malignancy. Conclusion AKI is a rare but potentially serious complication of ICIs. Temporal discontinuation of the implicated agent is of major importance while treatment with glucocorticoids may be critical for kindey function. Yet, constant vigilance and sustained collaboration among medical specialists are becoming essential in the increasing use of immunotherapy.