Data-Driven Stratification Reveals 3 Distinct Clinicopathologic Phenotypes in Renal Thrombotic Microangiopathy

Area of Science:

• Nephrology
• Pathology
• Immunology

Background:

• Thrombotic microangiopathy (TMA) is a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage.
• Accurate classification of TMA is crucial for guiding appropriate diagnostic and therapeutic interventions.

Purpose of the Study:

• To define distinct phenotypic subgroups of renal thrombotic microangiopathy (TMA) by integrating clinicopathologic data.
• To identify patterns suggestive of pathogenic features and etiologies within these subgroups.

Main Methods:

• Retrospective analysis of 283 patients with biopsy-confirmed renal TMA from 2010-2020.
• Application of consensus clustering using 64 clinicopathologic variables.

Main Results:

• Three distinct clusters were identified: Cluster 1 (immune-associated injury), Cluster 2 (toxic-related injury, including drug-induced TMA), and Cluster 3 (severe vascular lesion process with worst outcomes).
• Cluster 1 showed immune complex staining; Cluster 2 exhibited marked endothelial damage; Cluster 3 presented with acute vascular lesions and poor renal outcomes.
• Cluster 3 patients were younger, predominantly male, with severe hypertension and low GFR, experiencing high rates of renal failure.

Conclusions:

• Integrative clustering revealed 3 clinicopathologic phenotypes in TMA, suggesting immune-, toxic-, or severe vascular lesion-related drivers.
• These findings support a data-driven classification approach for TMA.
• This classification may help prioritize diagnostic and therapeutic considerations for patients with TMA.