Renal AA Amyloidosis in a Patient with Urothelial Carcinoma Treated with Avelumab: A Clinical Case Report

Introduction: AA amyloidosis is a rare disorder, mostly secondary to inflammatory diseases and characterized by overproduction of serum amyloid A (SAA) by the liver, that results in the aggregation of amyloid into cross-β-sheet fibrillar deposits of amyloid. Kidney is the most common organ involved by systemic AA amyloidosis. Case Description: 59 y.o female with past medical history of urothelial carcinoma of right ureter with hydronephrotic pouch of the right kidney and lymph node involvement diagnosed 2 years ago. Initially treated with Gemcitabine and Cisplatin, 4 months ago, started avelumab maintenance therapy, discontinued 1 month ago. Previously avelumab, serum creatinine (sCr) was 1.3 mg/dl with normal urine sediment. In February of 2025 she was presented with rapidly progressive kidney injury and nephrotic syndrome (NS). Laboratory findings show sCr 9.7 mg/dl, hypoalbuminemia 2.3 g/dl and urine protein-to-creatinine ratio of 13 g/g. Urine electrophoresis informed nonselective proteinuria (50% albumin, 50% other globulins). Abdomen CT had no changes. C3:95 mg/dl C4:38mg/dl. AntiPLA2R antibodies: negative. Blood electrophoresis without monoclonal peak. We started intermittent hemodialysis (HD) and glucocorticoids empirically. In the absence of renal functional recovery (HD dependent) and severe sustained NS in a patient with oncological pathology treated with immune checkpoint inhibitors (ICI), we decided to perform kidney biopsy. Renal AA amyloidosis was confirmed by histopathological results (Figure 1). Discussion: This is the first case report of renal AA amyloidosis in a patient under treatment with avelumab and active cancer. ICI are a cornerstone in the management of many oncological disorders achieving clinical success. Adverse effects are increasingly reported because of its use is in expansion. Renal toxicity is described as 1-2% and the most common pathological finding is acute interstitial nephritis. Recently AA amyloidosis was reported in 3 cases related to ICI but with cancer remission. In this case there is a relationship between initiation of avelumab and renal impairment, however cancer was not dormant.