Epigenetic regulation in AKI and kidney repair: mechanisms and therapeutic implications

Acute kidney injury (AKI) is a major public health concern associated with high morbidity and mortality. Despite decades of research, the pathogenesis of AKI remains incompletely understood and effective therapies are lacking. An increasing body of evidence suggests a role for epigenetic regulation in the process of AKI and kidney repair, involving remarkable changes in histone modifications, DNA methylation and the expression of various non-coding RNAs. For instance, increases in levels of histone acetylation seem to protect kidneys from AKI and promote kidney repair. AKI is also associated with changes in genome-wide and gene-specific DNA methylation; however, the role and regulation of DNA methylation in kidney injury and repair remains largely elusive. MicroRNAs have been studied quite extensively in AKI, and a plethora of specific microRNAs have been implicated in the pathogenesis of AKI. Emerging research suggests potential for microRNAs as novel diagnostic biomarkers of AKI. Further investigation into these epigenetic mechanisms will not only generate novel insights into the mechanisms of AKI and kidney repair but also might lead to new strategies for the diagnosis and therapy of this disease. A growing body of evidence suggests that epigenetic regulation is involved in the process of acute kidney injury (AKI) and kidney repair. This Review provides a general overview of the main epigenetic mechanisms that have been linked to AKI and discusses the challenges and therapeutic implications of these findings. Key points Acute kidney injury (AKI) and subsequent kidney repair are associated with substantial epigenetic changes that have important roles in the pathogenesis and outcome of AKI. An overall increase in histone acetylation (for example, with the use of histone deacetylase inhibitors) might attenuate AKI and promote kidney repair, but the enzymes and downstream genes that mediate these effects remain elusive. DNA methylation might also affect AKI and kidney repair via modulation of downstream genes, but the nature of this regulation remains largely unknown. MicroRNAs are important factors in the regulation of AKI and kidney repair, but they can be pathogenic or protective depending on the specific microRNA species. Additional research into the epigenetic mechanisms underlying AKI may lead to the discovery of novel biomarkers and therapies for AKI.