Renal AA amyloidosis associated with severe obesity: improvement in kidney function and proteinuria following semaglutide-associated weight loss

Abstract AA amyloidosis is driven by persistently elevated serum amyloid A (SAA) in chronic inflammation. Severe obesity has emerged as a potential inflammatory driver of renal AA amyloidosis. We report a 47-year-old man with prior sleeve gastrectomy who developed progressive kidney dysfunction and proteinuria after substantial weight regain. At presentation, he weighed 126 kg (body mass index, 45.2 kg/m2); serum creatinine was 4.3 mg/dL (estimated glomerular filtration rate, 15 mL/min/1.73 m2) and urine albumin-to-creatinine ratio (UACR) was 3.4 g/g. Kidney biopsy confirmed AA amyloidosis, while extensive evaluation for autoimmune, infectious, hereditary, malignant, and monoclonal causes was unrevealing. SAA was 80 mg/L with persistently elevated inflammatory markers. Semaglutide was initiated as part of a weight-management strategy. Following a 47-kg weight loss, creatinine decreased to 2.34 mg/dL, estimated glomerular filtration rate increased to 32 mL/min/1.73 m2, UACR declined to 1.0 g/g, and SAA fell to <10 mg/L, with improvement in C-reactive protein, erythrocyte sedimentation rate, and HbA1c. In the absence of another identifiable cause, the parallel improvement in SAA, systemic inflammation, proteinuria, and kidney function supports severe obesity as a potential inflammatory contributor to renal AA amyloidosis, although causality cannot be inferred from a single case.