Clinicopathologic spectrum and prognostic determinants in biopsy-proven thrombotic microangiopathy

Thrombotic microangiopathy (TMA) represents a heterogeneous clinicopathologic entity characterized by endothelial injury, microvascular thrombosis, and variable clinical outcomes. Data on prognostic factors in biopsy-proven TMA remain limited.

This retrospective single-center study included 46 adult patients with biopsy-proven TMA diagnosed between 2000 and 2025. Demographic, clinical, laboratory, histopathologic, and genetic parameters were analyzed. The composite adverse outcome was defined as death or progression to end-stage renal disease (ESRD). Logistic regression analysis was performed to identify prognostic determinants.

The most common etiologies were atypical hemolytic uremic syndrome (37.0%) and peripartum (pregnancy-associated) thrombotic microangiopathy (26.1%). During follow-up, 43.5% of patients progressed to end-stage renal disease or died. In univariate analyses, the presence of acute kidney injury at diagnosis (p=0.017) and lower estimated glomerular filtration rate (eGFR) (p=0.016) were associated with poorer outcomes. In contrast, both early treatment response within the first week (p=0.004) and peripartum TMA (p=0.042) were associated with more favorable outcomes. Notably, early treatment response remained significantly associated with improved outcomes in multivariate analyses (odds ratio [OR]=0.15; 95% confidence interval [CI], 0.03-0.75; p=0.021). Complement gene variants were identified in 5 of 10 tested patients, supporting a potential role for complement dysregulation in the pathogenesis of TMA.

Early on-treatment response may serve as a dynamic prognostic marker reflecting short-term disease trajectory in biopsy-proven TMA. These findings highlight the potential importance of timely recognition and close monitoring of treatment response in patients with biopsy-proven TMA.