Factors affecting the transition of acute kidney injury to chronic kidney disease: Potential mechanisms and future perspectives.

Acute kidney injury (AKI) is defined as a rapid loss of kidney function characterised by inflammation and cell death, ultimately leading to further functional and structural renal alterations. Based on experimental and epidemiological pieces of evidence, AKI may progress to chronic kidney disease (CKD) even after a recovery period due to maladaptive repair and other underlying mechanisms such as heightened Wnt signalling, overstimulation of the renin-angiotensin-aldosterone-system (RAAS) pathway, epigenetic alterations and inhibition of hypoxia-inducible factor (HIF) dependent defences. It has been reported that RAAS activation subsequent to renal insult mediates inflammatory and fibrotic mechanisms, which are a hallmark of CKD. Moreover, interesting evidence regarding the exposure-dependent dual role of Wnt signalling in both injury and repair, epigenetic changes underlying kidney disease suggest a potential therapeutic role of these pathways in AKI to CKD continuum. In addition, the hypoxia-independent renal benefits of erythropoietin such as anti-apoptosis and tubular regeneration also present an auspicious target which could be useful in clinical settings. In this review, the specific roles of these pathways in kidney disease, their pathological mechanisms and therapeutic strategies are discussed. Moreover, notable reports concerning stem cell therapy which hold promise in halting AKI-CKD continuum will be elaborated.