The Lonely Amyloid's Puzzle: Isolated Renal Apolipoprotein CII Amyloidosis - Familial or Isolated Occurrence?

Introduction: Apolipoprotein C-II (ApoC-II) amyloidosis is a rare, typically hereditary disorder characterized by the deposition of misfolded ApoC-II protein as amyloid fibrils, predominantly within the kidneys, frequently manifesting as nephrotic syndrome and renal impairment in older adults. We present an unusual instance of Apolipoprotein C-II amyloidosis distinguished by the absence of detectable genetic mutation and structural abnormalities. Case Description: A 63-year-old male with a history of Nephrotic CKD 3b complicated by pulmonary embolism on apixaban presented for proteinuria evaluation. Family history was notable for unspecified amyloid-related Deaths. Serum creatinine was 1.73 mg/dL, and his urine protein-to-creatinine ratio was 6.21 g/g (urine albumin creatinine ratio:3.8 g/g). ANA, C3 and C4, hepatitis and HIV panels, phospholipase A2 receptor antibodies and serum protein electrophoresis were unremarkable. He was started on losartan 25 mg and torsemide 10 mg. Kidney biopsy revealed diffuse glomerulosclerosis with amyloid infiltration, which was also observed patchily in the tubulointerstitium and focally in vessel walls, along with severe tubular atrophy and interstitial fibrosis Arterial changes included moderate intimal sclerosis. Immunofluorescence demonstrated non-specific IgM and C3 staining. Notably, both kappa and lambda staining were equally distributed throughout the tubulointerstitium. Liquid chromatography–tandem mass spectrometry (LC-MS/MS), identified AApoCII–type amyloid deposition with no structural abnormality, targeted sequencing of the APOC2 gene revealed no mutation and whole exome sequencing was unrevealing. Discussion: AApoCII amyloidosis commonly presents with renal involvement in older individuals, typically affecting the glomeruli and manifesting as proteinuria or nephrotic syndrome, often accompanied by progressive kidney disease. While some cases exhibit genetic underpinnings, including amino acid sequence variants and familial occurrence, the novelty of this case lies in the combination of its isolated renal involvement and the absence of protein structural abnormalities or detectable genetic mutations, particularly in the context of a family history of amyloidosis. Management remains primarily supportive.