Predictive Value and Potential of Targeting Complement Factor C3 in Patients with Renal Injury in Preeclampsia

Aim: The activation of the complement system is accompanied by the occurrence and development of preeclampsia, as well as kidney diseases. Here, the role of complement C3 [C3] in renal injury in preeclampsia was explored, and its potential application as an early diagnostic biomarker or drug target to ameliorate kidney injury induced by preeclampsia was preliminarily evaluated.

Method: A total of 48 subjects were included in the present study, and the complement C3 levels and renal function were analyzed.

Results: Patients with preeclampsia with severe features [sPe] had poorer renal function compared with the patients with preeclampsia. Urinary C3 levels could be used to distinguish between healthy controls, patients with preeclampsia, and patients with sPe. Increased renal inflammation and oxidative stress were notably increased in the preeclampsia mice with impaired renal function and attenuation of C3 activity using a C3 receptor antagonist, which reduced Pe-like symptoms and renal impairment, decreased serum blood urea nitrogen, creatinine, and urinary albumin levels, and decreased expression of the oxidative stress marker malondialdehyde, whilst increasing superoxide dismutase activity. In addition, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 ([HO-1) pathway was involved in the inhibition of complement C3 in the kidney.

Conclusion: Higher urinary C3 levels could be used to predict kidney damage as it was found that the activation of the Nrf2/HO-1 pathway attenuated C3 levels, and this resulted in increased renal impairment in preeclampsia.