Immunomodulatory Effects of Mesenchymal Stem Cells on Drug-Induced Acute Kidney Injury.

Qiuxia Han,Hanyu Zhu,Guangyan Cai,Jun He,Xiaochen Wang,Xiaonan Ding

doi:10.3389/fimmu.2021.683003

Abstract

Drug-induced nephrotoxicity is an important and increasing cause of acute kidney injury (AKI), which accounts for approximately 20% of hospitalized patients. Previous reviews studies on immunity and AKI focused mainly on ischemia-reperfusion (IR), whereas no systematic review addressing drug-induced AKI and its related immune mechanisms is available. Recent studies have provided a deeper understanding on the mechanisms of drug-induced AKI, among which acute tubular interstitial injury induced by the breakdown of innate immunity was reported to play an important role. Emerging research on mesenchymal stem cell (MSC) therapy has revealed its potential as treatment for drug-induced AKI. MSCs can inhibit kidney damage by regulating the innate immune balance, promoting kidney repair, and preventing kidney fibrosis. However, it is important to note that there are various sources of MSCs, which impacts on the immunomodulatory ability of the cells. This review aims to address the immune pathogenesis of drug-induced AKI versus that of IR-induced AKI, and to explore the immunomodulatory effects and therapeutic potential of MSCs for drug-induced AKI.

Highlights

In the past decade, pharmaceutical companies have developed many life-saving drugs for patients with cancer
We provide an in-depth, comprehensive summary of the immune pathogenesis of drug-induced acute kidney injury (AKI) and subsequent molecular mechanisms, including the different types of immune cells, cytokines, and related signaling pathways
The safest route of administration of mesenchymal stem cell (MSC) in clinical applications is through vascular injection; the number of MSCs that can reach the kidney is very small [47]

Summary

Introduction

Pharmaceutical companies have developed many life-saving drugs for patients with cancer. Some of these drugs are associated with nephrotoxicity, which remains an important and more frequent cause of acute kidney injury (AKI). Drug-induced AKI is a important category, accounting for 19–26% of AKI cases [2]. The use of nephrotoxic drugs is the main cause of severe AKI in critically ill patients. Drug-induced nephrotoxicity is one of the main factors leading to unsuccessful drug development, leading to loss of money and time in the pharmaceutical industry [3]. Approximately 19% of phase 3 clinical trial failures are caused by nephrotoxicity [3]

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