Role of C-Reactive Protein in Kidney Diseases

Background: C-reactive protein (CRP) is an acute phase protein and has been found to be a risk factor for acute renal injury (AKI) and chronic kidney diseases (CKD). However, role and mechanisms of CRP in AKI and CKD remain largely unclear. Summary: Clinically, elevated serum CRP is a risk factor or biomarker for patients with AKI and CKD. Interestingly, in critically ill COVID-19 patients, increased serum CRP is also associated with the development of AKI. Functionally, studies by using human CRP transgenic mouse models find that CRP is pathogenic and can function as a mediator for AKI and CKD as mice overexpressing human CRP are promoted AKI and CKD. Mechanistically, CRP can promote AKI and CKD via NF-κB and Smad3-dependent mechanisms. We found that CRP can activates Smad3 signaling directly and cause AKI via the Smad3-p27-dependent G1 cell cycle areast mechanism. Thus, targeting CRP-Smad3 signaling with a nuetralizing antibody or Smad3 inhibitor can inhibit AKI. Key Messages: CRP acts not only as a biomarker but also as a mediator for AKI and CKD. CRP can activate Smad3 to induce cell death and cause progressive renal fibrosis. Thus, targeting CPR-Smad3 signaling may represent as a promosing therapy for AKI and CKD.