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Abstract: SA-PO967

Differential Contributions of C5b-9 and C5a/C5aR1 Pathways to Thrombosis in Thrombotic Microangiopathy (TMA) Patients

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Liu, Xiaotian, Peking University First Hospital, Beijing, Beijing, China
  • Tan, Ying, Peking University First Hospital, Beijing, Beijing, China
Background

This study aimed to clarify the critical role of C5a/C5aR and C5b-9 pathways in macrovascular thrombosis (MAT) and renal microthrombosis (MIT) formations based on a complement-mediated thrombotic microangiopathy (C-TMA) cohort.

Methods

Seventy-three renal biopsy-proven C-TMA patients from 2012 to 2019 in Peking University First Hospital were collected. Amongst 73 C-TMA patients, 9 patients with pure MAT and 13 patients with pure MIT were selected. Their plasma and urinary C5a and soluble C5b-9 (sC5b-9) levels were evaluated, respectively. C5a receptors and C5b-9 depositions in renal biopsied specimens were assessed.

Results

Compared to patients with pure MAT, patients with pure MIT had lower levels of hemoglobin (P=0.008) and eGFR (P=0.049), and higher renal acute arterial scores (P=0.011). Plasma C5a and sC5b-9 levels were significantly higher in C-TMA patients with MAT than those with MIT (P=0.008, P=0.041, respectively). The mean optical density (MOD) of C5aR1 in the kidney was significantly higher in MAT patients than in those with MIT (P < 0.001). No significant difference was found in MOD of C5b-9 or C5L2 in the kidney or urinary C5a and C5b-9 levels between the two groups. However, urinary sC5b-9 level and renal depositions of C5b-9 were both associated with renal MIT formations (P=0.009; P=0.031, respectively).

Conclusion

MAT was not rare in C-TMA patients. The local C5b-9 and C5a/C5aR1 pathways might have differential contributions to MIT and MAT formations in the disease.

Funding

  • Government Support – Non-U.S.