Abstract
Increasing evidence has demonstrated the bidirectional link between acute kidney injury (AKI) and chronic kidney disease (CKD) such that, in the clinical setting, the new concept of a unified syndrome has been proposed. The pathophysiological reasons, along with the cellular and molecular mechanisms, behind the ability of a single, acute, apparently self-limiting event to drive chronic kidney disease progression are yet to be explained. This acute injury could promote progression to chronic disease through different pathways involving the endothelium, the inflammatory response and the development of fibrosis. The interplay among endothelial cells, macrophages and other immune cells, pericytes and fibroblasts often converge in the tubular epithelial cells that play a central role. Recent evidence has strengthened this concept by demonstrating that injured tubules respond to acute tubular necrosis through two main mechanisms: The polyploidization of tubular cells and the proliferation of a small population of self-renewing renal progenitors. This alternative pathophysiological interpretation could better characterize functional recovery after AKI.
Highlights
Despite the common belief of a generally benign nature, the profound, long-term implications of acute kidney injury (AKI) are appearing more and more evident
After a brief description of the main molecular pathways of the endothelial, inflammatory and fibrotic response to injury, we focus on the proximal tubular epithelial cell, the main player of the AKI-to-chronic kidney disease (CKD) transition [35]
AKI severity, duration and frequency are associated with the development of CKD, but even mild episodes are associated with an increased risk of disease progression
Summary
Despite the common belief of a generally benign nature, the profound, long-term implications of acute kidney injury (AKI) are appearing more and more evident. The consensus on a new definition of AKI has helped to improve the understanding of its long-term clinical consequences and to demonstrate a clear link between AKI episodes, their severity, and their outcome [6]. Despite continuous progresses in the field and the recent ability to better identify the molecular signature of different renal cell types following acute injury, the mechanisms that drive the transition to chronic disease remain debated [16,17]. Microvascular loss occurs along with increased fibrosis, worsening relative hypoxia within the kidney and in particular within the outer medulla. This is associated with changes in pericytes to adopt a pro-fibrotic myofibroblast phenotype. There is a need for the further investigation of the AKI-to-CKD transition as a public health priority
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