Increased trefoil factor 2 levels in patients with chronic kidney disease

Georg A Roth,Hendrik J Ankersmit,Elisa Einwallner,Franziska Roth-Walter,Bianca Tudor,Thomas Reiter,Claus G Krenn,Martin Haas,Diana Lebherz-Eichinger,Tatsuo Shimosawa

doi:10.1371/journal.pone.0174551

Abstract

In chronically damaged tissue, trefoil factor family (TFF) peptides ensure epithelial protection and restitution. In chronic kidney disease (CKD), TFF1 and TFF2 are reported to be upregulated. Especially in the early phase, CKD is associated with silently ongoing renal damage and inflammation. Moreover, many patients are diagnosed late during disease progression. We therefore sought to investigate the potential of TFF2 as biomarker for CKD. We followed 118 patients suffering from predialysis CKD and 23 healthy volunteers. TFF2 concentrations were measured using ELISA. Our results showed, that median TFF2 serum levels were significantly higher in patients with later CKD stages as compared to healthy controls (p < 0.001) or early stages (p < 0.001). In patients with mid CKD stages TFF2 serum levels were significantly higher than in healthy controls (p = 0.002). Patients with early or mid CKD stages had significantly higher TFF2 urine concentrations than later CKD stages (p < 0.001 and p = 0.009, respectively). Fractional TFF2 excretion differed significantly between early CKD stages and healthy controls (p = 0.01). ROC curve showed that TFF2 levels can predict different CKD stages (AUC > 0.75). In conclusion, urine and serum TFF2 levels of CKD patients show a different profile dependent on CKD stages. Whereas TFF2 urine levels continuously decreased with disease progression, TFF2 serum concentrations progressively increased from the early to later CKD stages, indicating changes in renal function and offering the potential to examine the course of CKD.

Highlights

For calculating estimated glomerular filtration rate (eGFR) the formular described in the 2002 guidelines was used to allow comparisons to already published studies dealing about Trefoil factor (TFF) levels in Chronic kidney disease (CKD). 118 patients with CKD stage 1 to 5 were included into the study during a follow-up appointment at the outpatient clinic of the Division of Nephrology and Dialysis. 23 healthy volunteers served as controls
The fractional TFF2 excretion was higher in early stages as compared to healthy controls, but not in mid and later stages of CKD (Fig 1C)
TFF2 serum levels were significantly higher in patients with vascular nephropathy or diabetic nephropathy as compared to patients suffering from glomerulonephritis (Table 2)

Summary

Introduction

Increased TFF2 levels in patients with chronic kidney disease minute per 1.73 m2 body-surface for a minimum of three months [1]. CKD patients are at increased risk of developing serious complications like cardiovascular diseases and even a slight decrease in GFR can result in anaemia or bone disease [1,2,3]. Trefoil factor (TFF) peptides have been shown to be upregulated in the damaged kidney, obviously to ameliorate epithelial destruction [8,9,10]. These proteins are secreted by several mucine-producing epithelial cells and are involved in mucousal healing. Restitution describes the recovery of mucosal continuity via elongation and cell migration to cover damaged denuded areas

Methods

Results

Discussion

Conclusion