Lactoferrin Contributes a Renoprotective Effect in Acute Kidney Injury and Early Renal Fibrosis.

Yung-Ho Hsu,I-Jen Chiu,Yi-Jie Chen,Yuh-Feng Lin,Hui-Wen Chiu,Yu-Hsuan Lee

doi:10.3390/pharmaceutics12050434

Abstract

Patients with acute kidney injury (AKI) who survive the acute stage are at notable risk for chronic kidney disease (CKD) progression. There is no single therapy that can effectively prevent the AKI to CKD transition. Autophagy is a cytoplasmic component degradation pathway and has complex functions in several diseases, such as renal fibrosis. Previous research has shown that lactoferrin has important functions in antioxidant defense and other defense systems, protecting kidneys against various injuries. The present study investigated the effect of lactoferrin in protecting against the AKI to CKD transition. We identified 62 consensus genes with two-fold changes in clinical kidney tissues from AKI and CKD patients. Among the 62 overlay genes, the mRNA levels of LTF were significantly upregulated in the kidney tissues of AKI and CKD patients. Lactoferrin induced autophagy via the activation of the AMPK and inhibition of Akt/mTOR pathway in human kidney proximal tubular cells. Lactoferrin suppressed oxidative stress-induced cell death and apoptosis by augmenting autophagy. Lactoferrin has an antifibrotic role in human kidney tubular cells. In a mouse model of folic acid-induced AKI to CKD transition, treatment with lactoferrin recovered renal function and further suppressed renal fibrosis through the inhibition of apoptosis and the induction of autophagy. These findings identify lactoferrin as a potential therapeutic target for the prevention of the AKI to CKD transition.

Highlights

Acute kidney injury (AKI) is a critical illness that is related to increased morbidity and mortality [1]
We found that the mRNA level of lactoferrin was elevated in the renal tissue of AKI and chronic kidney disease (CKD) patients compared to healthy individuals
We identified 62 overlay genes with two-fold changes (FC) in clinical kidney tissues from AKI and CKD patients (Figure 1A and Table S1)

Summary

Introduction

Acute kidney injury (AKI) is a critical illness that is related to increased morbidity and mortality [1]. AKI is a critical risk factor for the development of chronic kidney disease (CKD) and end-stage renal disease (ESRD) [3,4]. Research on the related mechanisms of AKI progression to CKD has mainly focused on persistent inflammatory response, mitochondrial dysfunction, microvascular endothelial cell injury and the abnormal activation of renal tubular epithelial cells. Inflammation, in turn, induces oxidative stress through the production of reactive oxygen species (ROS). These damaging events cause tissue injury by inducing necrosis, apoptosis and fibrosis [7]. Novel drugs or mechanisms that antifibrotic functions and accelerate fibrogenesis in treating the AKI to CKD transition must be developed

Results

Discussion

Conclusion