Recurrent Apolipoprotein C2 Variant Renal Amyloidosis After Kidney Transplant

Introduction: Apolipoprotein C-II amyloidosis (AApoC2) is an exceptionally rare hereditary renal amyloidosis caused by extracellular deposition of misfolded apolipoprotein C-II (APOC2) fibrils. First described in 2016, known mutations include APOC2 p.Lys41Thr and p.Glu69Val. AApoC2 primarily affects the kidneys, usually presenting in the sixth to eighth decades of life, with minimal extra-renal involvement. To date, no cases of kidney transplantation for AApoC2 have been reported. Case Description: We report a 71-year-old woman with hereditary AApoC2 diagnosed in 2014 at age 61. She underwent a living-donor kidney transplant in January 2017 at age 63. Eight years later, she developed nephrotic syndrome with a 24-hour urine protein of 9.2 grams and elevated creatinine. A kidney allograft biopsy in January 2025 revealed diffuse foot process effacement and numerous fibrillary structures in a thickened glomerular basement membrane with a mean thickness of 11.7 nm, consistent with recurrent amyloidosis (Figure 1). No evidence of AA amyloid, light chain, or monoclonal protein deposition was found. She began peritoneal dialysis in March 2025. There was no extra-renal amyloid involvement. Discussion: This case represents the first documented instance of AApoC2 recurrence in a kidney allograft. AApoC2 is thought to be a very slowly progressive disease with significant kidney disease only developing by the sixth decade of life or later. Recurrence observed less than a decade after transplant in this patient underscores the potential for disease relapse despite a successful early transplant course. This has implications for the counseling of patients with hereditary amyloidosis undergoing kidney transplantation. There is no known treatment so far for AApoC2.Figure 1: Electron microscopy showing fibrillary structures with an average thickness of 11.7 nm.