Role of C-Reactive Protein in Kidney Diseases

Abstract

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.

Combination of Honey and Nigella sativa Oil Reduce Oxidative Stress and Inflammation in Unilateral Ureteral Obstruction in Rats

“…6,15,16 C-reactive protein is a primary inflammatory marker in UUO rat model, driving early inflammation and renal fibrosis through FcgRI and TGF-b/Smad2/3 and NF-kB/p65 pathways. 17 In UUO rats, oxidative stress stimulates the Renin-Angiotensin System (RAS), activating the NF-κB cytokine transcription factor. NF-κB triggers the transcription of target genes, leading to inflammation and fibrosis.…”

Association between dietary inflammation index and albuminuria: results from the National Health and Nutrition Examination Survey

“…Numerous studies have shown that inflammation leads to a decline in kidney function. CRP is a risk factor for acute kidney injury (AKI) and CKD by leading to the decline of the estimated glomerular filtration rate (eGFR) ( 19 ). TNF-α directly affects kidney function by regulating kidney hemodynamics and excretory functions ( 20 ).…”

Evaluation of Inflammatory Parameters Following Extracorporeal Shock Wave Lithotripsy (ESWL) and Ureteroscopy for the Treatment of Proximal Ureteral Stones

“…Acute-phase CRP has been associated with both AKI and chronic kidney disorders (CKD). Nevertheless, the exact role and mechanisms of CRP in AKI and CKD remain largely unexplored [ 11 ]. It is worth noting that CRP serves as a valuable biomarker in the diagnosis of urinary tract infections [ 12 ].…”