Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A protein

Lancet. 2001 Jul 7;358(9275):24-9. doi: 10.1016/S0140-6736(00)05252-1.


Background: Reactive systemic (AA, secondary) amyloidosis occurs in chronic inflammatory diseases, and most patients present with nephropathy. The amyloid fibrils are derived from the circulating acute-phase reactant serum amyloid A protein (SAA), but the relation between production of fibril precursor protein, amyloid load, and clinical outcome in AA and other types of amyloidosis is unclear.

Methods: We studied amyloidotic organ function and survival prospectively for 12-117 months in 80 patients with systemic AA amyloidosis in whom serum SAA concentration was measured monthly and visceral amyloid deposits were assessed annually by serum amyloid P component scintigraphy. Underlying inflammatory diseases were treated as vigorously as possible.

Findings: Amyloid deposits regressed in 25 of 42 patients whose median SAA values were within the reference range (<10 mg/L) throughout follow-up, and amyloidotic organ function stabilised or improved in 39 of these cases. Outcome varied substantially among patients whose median SAA concentration exceeded 10 mg/L, but amyloid load increased and organ function deteriorated in most of those whose SAA was persistently above 50 mg/L. Estimated survival at 10 years was 90% in patients whose median SAA was under 10 mg/L, and 40% among those whose median SAA exceeded this value (p=0.0009).

Interpretation: Although isolated amyloid fibrils are stable in vitro, AA amyloid deposits exist in a state of dynamic turnover, and outcome is favourable in AA amyloidosis when the SAA concentration is maintained below 10 mg/L. The potential for amyloid to regress and for the function of amyloidotic organs to recover support therapeutic strategies to decrease the supply of amyloid fibril precursor proteins in amyloidosis generally.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amyloidosis / blood
  • Amyloidosis / diagnostic imaging*
  • Child
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Iodine Radioisotopes
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Radionuclide Imaging
  • Serum Amyloid A Protein / metabolism*
  • Serum Amyloid P-Component*
  • Whole-Body Counting


  • Iodine Radioisotopes
  • Serum Amyloid A Protein
  • Serum Amyloid P-Component