Idiopathic AA Renal Amyloidosis Treated with Tocilizumab — A Case Report

Background Amyloidosis represents a heterogeneous group of disorders characterized by the deposition of misfolded protein. Among its subtypes, serum amyloid A (AA) amyloidosis arises when persistent systemic inflammation drives hepatic production of SAA. Excess SAA misfolds into insoluble fibrils that deposit in organs such as the kidneys, causing progressive proteinuria, loss of renal function and eventual renal failure. Standard management aims to control the underlying inflammation to reduce SAA production and halt further amyloid deposition. For example, interleukin-6 blockade with tocilizumab, which suppresses SAA production, has shown encouraging results in small series of patients with secondary amyloidosis. [1,2] In rare cases without an identifiable source of inflammation, however, no targeted therapies have been shown to be effective.

Case Report We report a 48-year-old female first found incidentally at the age of 37 to have renal impairment. Over the past decade, her eGFR had declined to 12mL/min/1.73m², with 3g/L of proteinuria. Renal biopsy in 2020 confirmed widespread AA amyloid deposits with severe interstitial fibrosis and 11/16 glomeruli globally sclerosed, with SAA concentrations exceeding 16,000ng/mL. Throughout her entire course, she had no infectious, rheumatologic or constitutional symptoms. Other than a RF titer of 30 IUx103/L, extensive investigations were negative, including bone marrow biopsy, rheumatologic markers (CCP, ANA, dsDNA, C3/C4, ANCA, ESR, CRP) and infectious serologies (hepatitis, syphilis, schistosoma, strongyloides, whipples, tuberculosis, HIV, HTLV, filariasis). A thorough genetic investigation was also negative including sequencing for the SAA1 gene, panels containing genes associated with hereditary amyloidosis and autoinflammatory diseases, as well as a research exome. A brief trial of colchicine was initially trialed but stopped due to worsening kidney function. Tocilizumab 160mg SC every 2 weeks was initiated in December 2024 in an attempt to suppress hepatic SAA production. A year after, SAA levels fell from >16,000 to 5,427ng/mL. Her GFR stabilized at 13 mL/min/1.73m², and dialysis has not yet been required at the time of writing.

Conclusion Idiopathic AA amyloidosis is a therapeutic challenge due to the condition’s rarity and lack of standard therapies. While there are numerous publications demonstrating the efficacy of tocilizumab in secondary AA amyloidosis,[1-3] our case is the first we are aware of, describing this therapeutic effect in idiopathic AA amyloidosis. This case underscores the central role of interleukin-6 in SAA production and may form the foundation for future studies with more patients over a longer duration to further explore the disease-modifying benefits of tocilizumab in idiopathic AA amyloidosis.

References [1.] Okuda Y. Mod Rheumatol 2019;29:268-74. [2.] Courties A. Amyloid 2015;22:84-92. [3.] Yamagata A. BMC Nephrol 2017;18:377.