Acute kidney injury (AKI) is a major kidney disease characterized by an abrupt loss of renal function. Accumulating evidence indicates that incomplete or maladaptive repair after AKI can result in kidney fibrosis and the development and progression of chronic kidney disease (CKD). Hypoxia, a condition of insufficient supply of oxygen to cells and tissues, occurs in both acute and chronic kidney diseases under a variety of clinical and experimental conditions. Hypoxia-inducible factors (HIFs) are the “master” transcription factors responsible for gene expression in hypoxia. Recent researches demonstrate that HIFs play an important role in kidney injury and repair by regulating HIF target genes, including microRNAs. However, there are controversies regarding the pathological roles of HIFs in kidney injury and repair. In this review, we describe the regulation, expression, and functions of HIFs, and their target genes and related functions. We also discuss the involvement of HIFs in AKI and kidney repair, presenting HIFs as effective therapeutic targets.

Acute kidney injury (AKI) is a major kidney disease characterized by rapid decline of renal function. Besides its acute consequence of high mortality, AKI has recently been recognized as an independent risk factor for chronic kidney disease (CKD). Maladaptive or incomplete repair of renal tubules after severe or episodic AKI leads to renal fibrosis and, eventually, CKD. Recent studies highlight a key role of mitochondrial pathology in AKI development and abnormal kidney repair after AKI. As such, timely elimination of damaged mitochondria in renal tubular cells represents an important quality control mechanism for cell homeostasis and survival during kidney injury and repair. Mitophagy is a selective form of autophagy that selectively removes redundant or damaged mitochondria. Here, we summarize our recent understanding on the molecular mechanisms of mitophagy, discuss the role of mitophagy in AKI development and kidney repair after AKI, and present future research directions and therapeutic potential.