Potential targeted therapy and diagnosis based on novel insight into growth factors, receptors, and downstream effectors in acute kidney injury and acute kidney injury-chronic kidney disease progression

Abstract

AbstractAcute kidney injury (AKI) is defined as a rapid decline in renal function and is characterized by excessive renal inflammation and programmed death of resident cells. AKI shows high morbidity and mortality, and severe or repeated AKI can transition to chronic kidney disease (CKD) or even end-stage renal disease (ESRD); however, very few effective and specific therapies are available, except for supportive treatment. Growth factors, such as epidermal growth factor (EGF), insulin-like growth factor (IGF), and transforming growth factor-β (TGF-β), are significantly altered in AKI models and have been suggested to play critical roles in the repair process of AKI because of their roles in cell regeneration and renal repair. In recent years, a series of studies have shown evidence that growth factors, receptors, and downstream effectors may be highly involved in the mechanism of AKI and may function in the early stage of AKI in response to stimuli by regulating inflammation and programmed cell death. Moreover, certain growth factors or correlated proteins act as biomarkers for AKI due to their sensitivity and specificity. Furthermore, growth factors originating from mesenchymal stem cells (MSCs) via paracrine signaling or extracellular vesicles recruit leukocytes or repair intrinsic cells and may participate in AKI repair or the AKI-CKD transition. In addition, growth factor-modified MSCs show superior therapeutic potential compared to that of unmodified controls. In this review, we summarized the current therapeutic and diagnostic strategies targeting growth factors to treat AKI in clinical trials. We also evaluated the possibilities of other growth factor-correlated molecules as therapeutic targets in the treatment of AKI and the AKI-CKD transition.