A Cautionary Tale: An Instructive Case of Recognising Non‐Amyloid Light Chain Renal Amyloidosis

Amyloidosis is a group of diseases characterised by tissue deposition of misfolded proteins, leading to organ dysfunction without appropriate therapy. Fibrinogen A α-chain amyloidosis is a rare hereditary amyloidosis that can be difficult to distinguish from other causes of renal amyloidosis. We report on a 66-year-old female who presented with deteriorating kidney function. Serum kappa/lambda free light chain ratio was normal with no detectable paraprotein. Kidney biopsy showed marked glomerular expansion and architectural destruction due to amyloid deposition with no vascular amyloid deposits and moderate kappa staining on immunohistochemistry. Despite bone marrow aspirate and trephine showing no evidence of plasma cell dyscrasia, light chain amyloidosis was diagnosed, and she was treated with chemotherapy, eventually progressing to kidney failure. Subsequent genetic testing revealed the amyloidogenic variant of fibrinogen A α due to mutation Glu526Val, confirming a diagnosis of fibrinogen A α-chain amyloidosis and not light chain amyloidosis. She received a deceased donor kidney transplant and was treated with doxycycline for its anti-fibrillogenesis effect with no amyloid recurrence on post-transplant surveillance biopsies, satisfactory kidney function and no proteinuria 6 years post-transplant. Renal amyloidosis cannot be attributed to the light chain subtype without evidence of plasma cell dyscrasia. Understanding of patterns of amyloid deposition in all renal amyloidosis subtypes is necessary, and genetic testing and mass spectrometry should be considered when immunohistochemistry is inconclusive. Correct subtyping of renal amyloidosis is crucial to avoid unnecessary toxicity from chemotherapy and determine the risk of recurrence for kidney transplantation. A multidisciplinary team approach with amyloidosis expertise is recommended.