SerpinA3 in the Early Recognition of Acute Kidney Injury to Chronic Kidney Disease (CKD) transition in the rat and its Potentiality in the Recognition of Patients with CKD

Abstract

Recognizing patients at early phases of chronic kidney disease (CKD) is difficult, and it is even more challenging to predict acute kidney injury (AKI) and its transition to CKD. The gold standard to timely identify renal fibrosis is the kidney biopsy, an invasive procedure not usually performed for this purpose in clinical practice. SerpinA3 was identified by high-resolution-mass-spectrometry in urines from animals with CKD. An early and progressive elevation of urinary SerpinA3 (uSerpinA3) was observed during the AKI to CKD transition together with SerpinA3 relocation from the cytoplasm to the apical tubular membrane in the rat kidney. uSerpinA3/alpha-1-antichymotrypsin was significantly increased in patients with CKD secondary to focal and segmental glomerulosclerosis (FSGS), ANCA associated vasculitis (AAV) and proliferative class III and IV lupus nephritis (LN). uSerpinA3 levels were independently and positively associated with renal fibrosis. In patients with class V LN, uSerpinA3 levels were not different from healthy volunteers. uSerpinA3 was not found in patients with systemic inflammatory diseases without renal dysfunction. Our observations suggest that uSerpinA3 can detect renal fibrosis and inflammation, with a particular potential for the early detection of AKI to CKD transition and for the differentiation among lupus nephritis classes III/IV and V.

Potent Therapy and Transcriptional Profile of Combined Erythropoietin-Derived Peptide Cyclic Helix B Surface Peptide and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in Mice

“…SERPINA3 expression was also found in rat kidneys, which can detect renal inflammation and fibrosis after IR injury and also serve as a urinary marker for early detection of AKI to CKD transition (Sanchez-Navarro et al, 2019). Because murine SERPINA3M (FC = 8.289, Table 3) is a likely orthologue of human SERPINA3, the two proteins may have similar structural and kinetical characterization.…”

Global Proteome and Phosphoproteome Characterization of Sepsis-induced Kidney Injury

“…Serine protease inhibitors are usually found to be increased during acute inflammation and act by modulating protease activities 52, 53 . Recently, Serpina3n was found to be elevated in the urine of rats with early AKI-to-CKD transition and relocated from cytoplasm to apical tubular cell membranes 54 . In our immunoblot analysis, we found one of these serine protease inhibitors, α-1-antitrypsin, to be significantly increased at day 2 ( Figure 5, M and N).…”

Potent Therapy and Transcriptional Profile of Combined Erythropoietin Derived Peptide CHBP and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in mice

“…In human, SERPINA3, a member of the serpin superfamily of protease inhibitors, could limit in ammation by targeting cathepsin family (proin ammatory enzymes) (Horvath et al, 2005;Lannan et al, 2012). SERPINA3 expression was also found in rat kidneys, which can detect renal in ammation and brosis after IR injury and also serve as a urinary marker for early detection of AKI to CKD transition (Sanchez-Navarro et al, 2019). Because murine SERPINA3M (FC = 8.289, Table 3) is a likely orthologue of human SERPINA3, the two proteins may have similar structural and kinetical characterization.…”