Objective: To define phenotypic subgroups of thrombotic microangiopathy (TMA) by integrating clinicopathological data to identify patterns suggestive of pathogenic features and etiologies. Patients and Methods:We retrospectively analyzed 283 patients with biopsy-confirmed renal TMA between January 1, 2010 and December 31, 2020.Sixty-four clinicopathological variables were applied in consensus clustering.Results: Three distinct clusters were identified.Cluster 1 (n=78), predominantly female (64%), was enriched for drug-induced (29%), lupus-associated (12%), and post-bone marrow transplant TMA (10%).It showed wide immune-complex staining (IgM, C3, kappa, lambda) and subendothelial deposits (21%), suggestive of immune-associated injury.Cluster 2 (n=92) included the oldest patients (5418 years) and was dominated by drug-induced TMA (23%; one third due to VEGF inhibitor bevacizumab) and monoclonal gammopathy-associated TMA (11%).It demonstrated marked endothelial damage (71%) and mesangiolysis (72%) with little immune staining, suggesting a toxic related injury.Cluster 3 (n=113) exhibited the worst outcomes, with 80% progressing to renal failure compared with 31% in cluster 1 and 34% in cluster 2. This cluster was characterized by the youngest age (4514 years), mostly male (59%), severe hypertension (66%), and low eGFR (10 ml/min/1.73m 2 , IQR 7-16).Biopsies showed acute vascular lesions-wrinkling of capillary tufts (65%), fibrin thrombi (59%), mucoid intimal edema (75%), and onion-skin-type hyperplasia (49%)-with minimal deposits (0.9%), suggesting a severe vascular-lesion process. Conclusion:Integrative clustering of clinical and histologic data in TMA identified three clinicopathologic phenotypes that may suggest underlying immune, toxic, or severe vascular-lesion
Moubarak et al. (Wed,) studied this question.