Clinical phenotypes and etiologic subtypes of thrombotic microangiopathy in systemic lupus erythematosus
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ID: 323269
2026
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Abstract
Abstract Background Thrombotic microangiopathy (TMA) is a rare and severe complication of systemic lupus erythematosus (SLE). While classically defined by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage, TMA may also present as a renal-limited process requiring histologic diagnosis. Data characterizing the clinical phenotypes, histologic patterns, etiologic subtypes, and outcomes of SLE-associated TMA remain limited. Methods We conducted a retrospective cohort study of adults with SLE-TMA diagnosed between 2004 and 2024 at a tertiary referral center. TMA was defined by either hematologic criteria and/or kidney biopsy findings. Patients were categorized as having renal-hematologic TMA (RH-TMA) or renal-limited TMA (RL-TMA). Etiologic adjudication was performed using predefined clinical criteria, incorporating validated probability scores and serologic evaluation. Clinical characteristics, histologic findings, treatment, and long-term outcomes were analyzed by survival analyses. Results A total of 124 patients were included. The median age was 29 years and 90% were female. Kidney biopsy was performed in 81% of cases. Nearly half of cases (48%) presented as RL-TMA without hematologic manifestations. Compared with RH-TMA, RL-TMA was associated with a higher prevalence of chronic vascular lesions (aOR 2.84, 95%CI 1.04–7.78) and an increased risk of renal relapse (aHR 2.67, 95%CI 1.17–6.09), while mortality was higher in RH-TMA. Histologic activity pattern (acute vs. chronic lesions) was not associated with renal outcomes. Etiologic adjudication suggested three predominant phenotypes: suspected complement-mediated TMA (59.7%), antiphospholipid syndrome nephropathy (34.7%), and TTP-like TMA (5.6%). Patients with TTP-like presentations had more severe hematologic involvement but favorable renal recovery among survivors. Conclusion SLE-associated TMA frequently presents as a renal-limited syndrome requiring biopsy for diagnosis. A phenotype-based approach identifies clinically relevant subgroups with distinct renal trajectories, even in the absence of systematic biomarker confirmation. These findings support a pragmatic diagnostic framework for SLE-TMA and highlight the importance of kidney biopsy in patients without overt hematologic features.
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| Authors | André Fortanell-Meza, Daniela Edith Sánchez-Mejía, Ana Barrera‐Vargas, Melvin Barish Matías-Martínez, Julio C Santos-Fuentes, André Méndez Bolaños-Cacho, J Esteban Reyes-Moreno, Norma Uribe‐Uribe, Fernanda Zavala‐Miranda, Juan M. Mejía‐Vilet |
| Journal | nephrology dialysis transplantation |
| Year | 2026 |
| DOI |
10.1093/ndt/gfag167
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| URL | |
| Keywords | Keywords not found |
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