Abstract
Acute kidney injury (AKI) is characterized by a rapid deterioration of kidney function, representing a global healthcare concern. In addition, AKI survivors frequently develop chronic kidney disease (CKD), contributing to a substantial proportion of disease burden globally. Yet, over the past 30 years, the burden of CKD has not declined to the same extent as many other important non-communicable diseases, implying a substantial deficit in the understanding of the disease progression. The assumption that the kidney response to AKI is based on a high proliferative potential of proximal tubular cells (PTC) caused a critical confounding factor, which has led to a limited development of strategies to prevent AKI and halt progression toward CKD. In this review, we discuss the latest findings on multiple mechanisms of response related to cell cycle behavior of PTC upon AKI, with a specific focus on their biological relevance. Collectively, we aim to (1) provide a new perspective on interpreting cell cycle progression of PTC in response to damage and (2) discuss how this knowledge can be used to choose the right therapeutic window of treatment for preserving kidney function while avoiding CKD progression.
Highlights
Acute kidney injury (AKI), a syndrome characterized by an acute deterioration of kidney function, represents a global healthcare issue [1,2,3]
Many epidemiologic studies demonstrated that AKI survivors frequently develop chronic kidney disease (CKD), which is associated with a high cardiovascular risk and the possibility of progression toward end-stage kidney disease (ESKD) [4]
We aimed to describe and interpret recent data relating to the role of cell cycle response during AKI and in the following CKD progression
Summary
Acute kidney injury (AKI), a syndrome characterized by an acute deterioration of kidney function, represents a global healthcare issue [1,2,3]. Renal function returns to baseline after an acute insult, AKI survivors frequently develop CKD [22], which is incompatible with the idea that the cell cycle re-entry of PTC repopulates and regenerates the nephron. To explain this apparent inconsistency, several groups reported that after a severe injury, PTC remain arrested in the G2/M phase of the cell cycle, leading to the so-called maladaptive repair [6,7]. Evidence for the existence of alternative cell cycles generating polyploid PTC has further complicated this scenario [23] This would suggest that the current paradigm about kidney repair mechanisms is oversimplified and requires revision. We aim to summarize the major findings on PTC cell cycle behavior in response to AKI, shedding some light on the processes that promote CKD progression and helping to advance our understanding of AKI pathophysiology
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