Lachmann Helen J, Goodman Hugh J B, Gilbertson Janet A, Gallimore J Ruth, Sabin Caroline A, Gillmore Julian D, Hawkins Philip N
National Amyloidosis Centre and Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, London.
N Engl J Med. 2007 Jun 7;356(23):2361-71. doi: 10.1056/NEJMoa070265.
Deposition of amyloid fibrils derived from circulating acute-phase reactant serum amyloid A protein (SAA) causes systemic AA amyloidosis, a serious complication of many chronic inflammatory disorders. Little is known about the natural history of AA amyloidosis or its response to treatment.
We evaluated clinical features, organ function, and survival among 374 patients with AA amyloidosis who were followed for a median of 86 months. The SAA concentration was measured serially, and the amyloid burden was estimated with the use of whole-body serum amyloid P component scintigraphy. Therapy for inflammatory diseases was administered to suppress the production of SAA.
Median survival after diagnosis was 133 months; renal dysfunction was the predominant disease manifestation. Mortality, amyloid burden, and renal prognosis all significantly correlated with the SAA concentration during follow-up. The risk of death was 17.7 times as high among patients with SAA concentrations in the highest eighth, or octile, (>or=155 mg per liter) as among those with concentrations in the lowest octile (<4 mg per liter); and the risk of death was four times as high in the next-to-lowest octile (4 to 9 mg per liter). The median SAA concentration during follow-up was 6 mg per liter in patients in whom renal function improved and 28 mg per liter in those in whom it deteriorated (P<0.001). Amyloid deposits regressed in 60% of patients who had a median SAA concentration of less than 10 mg per liter, and survival among these patients was superior to survival among those in whom amyloid deposits did not regress (P=0.04).
The effects of renal dysfunction dominate the course of AA amyloidosis, which is associated with a relatively favorable outcome in patients with SAA concentrations that remain in the low-normal range (<4 mg per liter).
源自循环急性期反应物血清淀粉样蛋白A蛋白（SAA）的淀粉样原纤维沉积会导致系统性AA淀粉样变性，这是许多慢性炎症性疾病的严重并发症。关于AA淀粉样变性的自然病史或其对治疗的反应知之甚少。
我们评估了374例AA淀粉样变性患者的临床特征、器官功能和生存情况，这些患者的中位随访时间为86个月。连续测量SAA浓度，并使用全身血清淀粉样蛋白P成分闪烁扫描估计淀粉样蛋白负荷。对炎症性疾病进行治疗以抑制SAA的产生。
诊断后的中位生存期为133个月；肾功能障碍是主要的疾病表现。死亡率、淀粉样蛋白负荷和肾脏预后均与随访期间的SAA浓度显著相关。SAA浓度处于最高八分位数（≥155毫克/升）的患者死亡风险是处于最低八分位数（<4毫克/升）患者的17.7倍；而处于次低八分位数（4至9毫克/升）的患者死亡风险是其4倍。肾功能改善的患者随访期间SAA浓度中位数为6毫克/升，肾功能恶化的患者为28毫克/升（P<0.001）。SAA浓度中位数低于10毫克/升的患者中，60%的患者淀粉样蛋白沉积消退，这些患者的生存期优于淀粉样蛋白沉积未消退的患者（P=0.04）。
肾功能障碍的影响主导了AA淀粉样变性的病程，对于SAA浓度保持在低正常范围（<4毫克/升）的患者，其预后相对较好。
