Patients with hypertension-associated thrombotic microangiopathy may present with complement abnormalities

Area of Science:

• Nephrology
• Immunology
• Genetics

Background:

• Thrombotic microangiopathy (TMA) is endothelial damage linked to conditions like malignant hypertension.
• Complement dysregulation is increasingly associated with TMA syndromes, notably atypical hemolytic uremic syndrome.

Purpose of the Study:

• To investigate the role of complement activation in patients with biopsy-proven renal TMA secondary to severe hypertension.
• To identify genetic complement abnormalities in this patient cohort.

Main Methods:

• Analysis of nine patients with biopsy-proven renal TMA and severe hypertension.
• Genetic mutation screening for complement genes (C3, CFI, CD46, CFH) and CFH-H3 haplotype.
• Assessment of complement activation markers (sC5b-9) and renal deposits (C3c, C5b-9).

Main Results:

• Six of nine patients had complement gene mutations (C3, CFI, CD46, CFH).
• Elevated sC5b-9 and renal C3c/C5b-9 deposits confirmed in vivo complement activation.
• Patients with complement defects showed a higher progression to end-stage renal disease and recurrence post-transplant.

Conclusions:

• A subset of hypertension-associated TMA is complement-mediated, carrying a poor prognosis.
• Genetic complement testing is crucial for patients with severe hypertension and renal TMA.
• Early diagnosis and intervention can guide treatment and prophylactic strategies.