先前在初发非典型溶血性尿毒症（HUS）中鉴定到补体缺陷作为主要推动因素改变了血栓性微血管病（TMA）的格局，促进了靶向治疗和更好的患者结局。相比之下，关于特定疾病或情况相关联的TMA的表现、遗传和结局，即所谓的继发性TMA，人们知之甚少。在此，我们评估了欧洲两个参考中心在2009年至2019年期间连续住院患有第一次TMA的患者中继发性TMA与其他TMA的相对发病率、临床和遗传谱以及长期结局。研究期间，共有336名患者因初发TMA住院。病因包括非典型HUS的49例（15%）；血栓性血小板减少性紫癜的29例（9%）；志贺氏菌毒素相关HUS的70例（21%）以及继发性TMA的188例（56%）。继发性TMA的主要原因是造血干细胞移植（n=56，30%），实体器官移植（n=44，23%）和恶性高血压（n=25，13%）。在非典型HUS患者中，补体基因中的罕见变异在32/49（65%）患者中被鉴定出来，继发性TMA的患者中为8/64（13%）；其中有病理或可能有病理的变异分别在49/24（49%）和64/2（3%）的患者中（P<0.001）。在中位随访1157天后，死亡或肾衰竭发生在非典型HUS、血栓性血小板减少性紫癜、志贺氏菌毒素相关HUS和继发性TMA的14例（29%）、8例（28%）、5例（7%）和121例（64%）患者中。未经调整和经过调整的Cox回归表明，较高死亡或肾衰竭风险的患者为继发性TMA（未经调整风险比3.35，95%置信区间1.85-6.07，P<0.001；调整后风险比4.11，95%置信区间2.00-8.46，P<0.001；以非典型HUS为参考）。继发性TMA是TMA的主要原因，与高死亡和进展为肾衰竭的风险独立相关。 版权所有©2023年美国肾脏学会。

The identification of complement defects as major drivers of primary atypical hemolytic uremic syndrome (HUS) has transformed the landscape of thrombotic microangiopathies (TMA), leading to the development of targeted therapies and better patients' outcomes. In contrast, little is known about the presentation, genetics and outcomes of TMA associated with specific diseases or conditions, also referred to as secondary TMA.Here we assessed the relative incidence, clinical and genetic spectra, and long-term outcomes of secondary TMA vs. other TMAs in consecutive patients hospitalized with a first episode of TMA from 2009 to 2019 at two European reference centers.During the study period, 336 patients were hospitalized with a first episode of TMA. Etiologies included atypical HUS in 49 (15%); thrombotic thrombocytopenic purpura in 29 (9%); shigatoxin-associated HUS in 70 (21%), and secondary TMA in 188 (56%). The main causes of secondary TMA were hematopoietic stem cell transplantation (n=56, 30%), solid organ transplantation (n=44, 23%) and malignant hypertension (n=25, 13%). Rare variants in complement genes were identified in 32/49 (65%) patients with atypical HUS and 8/64 (13%) with secondary TMA; pathogenic or likely pathogenic variants were found in 24/49 (49%) and 2/64 (3%) of them, respectively (P<0.001). After a median follow-up of 1157 days, death or kidney failure occurred in 14 (29%), 8 (28%), 5 (7%) and 121 (64%) patients with atypical HUS, thrombotic thrombocytopenic purpura, shigatoxin-associated HUS and secondary TMA, respectively. Unadjusted and adjusted Cox regressions showed that patients with secondary TMA had the highest risk of death or kidney failure (unadjusted hazard ratio 3.35, 95% confidence interval 1.85-6.07, P<0.001; adjusted hazard ratio 4.11, 95% confidence interval 2.00-8.46, P<0.001; considering atypical HUS as reference).Secondary TMA represent the main cause of TMA and are independently associated with a high risk of death and progression to kidney failure.Copyright © 2023 by the American Society of Nephrology.