Complement abnormality predisposes to the development of malignant hypertension-associated thrombotic microangiopathy disease.

Abstract

Background: Thrombotic microangiopathy (TMA) is a major complication of malignant hypertension (mHTN). Abnormal complement activation has been recognized as a key determinant of TMA, but less is known about the prognostic significance of complement abnormality in patients with mHTN-associated TMA.

Methods: A prospective cohort study was performed in patients with mHTN. All participants had concomitant TMA proven by kidney biopsy after admission between 2008 and 2023, and were divided into normal and abnormal complement groups based on serum C3 and C4 levels. Cox regression models were used to identify risk factors for renal prognosis.

Results: A total of 189 mHTN patients with TMA were enrolled in the current study, including 161 (85.2%) patients with normal complement levels and 28 (14.8%) patients with abnormal complement levels. Compared to the normal complement group, patients in the abnormal complement group had lower levels of BMI, hemoglobin, and platelet counts, and more intravascular erythrocyte fragments (21.4% vs 7.5%, P = .02). Notably, a substantial glomerular deposition of C3c and C5b-9 was observed in the abnormal complement group, indicating complement activation in vivo. Importantly, abnormal complement levels were independently associated with worse renal function recovery [hazard ratio (HR), 0.368; 95% CI, 0.140-0.970; P = .043]. In addition, the glomerular sclerosis ratio (HR, 0.971; 95% CI, 0.953-0.989; P = .002) remained an independent predictor of poor renal outcomes.

Conclusions: Patients with abnormal complement levels have worse renal prognosis, suggesting that complement abnormality predisposes to the progression of mHTN-associated TMA disease.