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

Andrea Sánchez-Navarro,Juan M Mejía-Vilet,Gerardo Gamba,Diego L Carrillo-Pérez,Rosalba Pérez-Villalva,Norma A Bobadilla,Brenda Marquina-Castillo

doi:10.1038/s41598-019-46601-1

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.

Highlights

Chronic kidney disease (CKD) is a silent disease that is often not recognized in clinical practice until the global renal function is impaired or proteinuria is detected in urine assays
It was previously speculated that patients who completely recovered from an Acute kidney injury (AKI) episode had no further repercussions on kidney function and structure; recent evidence based on epidemiological and experimental observations has demonstrated that in many cases, AKI leads to CKD8–13
We identified the abnormal presence of serpinA3 in urine samples from animals with chronic kidney disease (CKD) by high-resolution mass spectrometry, and here, we present evidence that uSerpinA3 is a potentially useful diagnostic marker to detect the AKI to CKD transition and CKD from different etiologies

Summary

Introduction

Chronic kidney disease (CKD) is a silent disease that is often not recognized in clinical practice until the global renal function is impaired or proteinuria is detected in urine assays. By the end of the study, all animals developed CKD and exhibited higher amounts of urine proteins between 55 and 72 kDa compared to the control group (Fig. 1A).

Results

Conclusion