Kathleen D Liu1, Paul R Brakeman. 1. Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. Kathleen.Liu@ucsf.edu
Abstract
OBJECTIVE: To review the cellular and molecular mechanisms of renal repair and recovery after acute kidney injury (AKI). DATA SOURCE: The data were summarized from published research articles. RESULTS: In AKI, there is an acute inflammatory response, epithelial cell necrosis and apoptosis, and shedding of epithelial cells into the tubular lumen. Recent work demonstrates that repopulation of damaged renal tubules occurs primarily from proliferation of tubular epithelial cells and resident renal-specific stem cells, with some contribution of paracrine factors from bone marrow-derived mesenchymal stem cells. In addition, growth factors seem to play a critical role in the repair process in animal models of renal injury. However, attempts to use growth factors in the clinical setting to attenuate human AKI or accelerate renal repair have not yet been successful. The endothelium also plays a critical role in the pathogenesis of AKI. Lastly, in human studies, the effect of dialysis on renal recovery remains poorly understood. CONCLUSIONS: Experimental animal models of AKI demonstrate that renal recovery and repair involves proliferation of tubular epithelial cells and stem cell populations and the coordinated contribution of multiple growth factors. Future efforts to improve recovery from AKI and improve patient outcomes may include novel therapies based on manipulation of populations of stem cells and augmenting repopulation of renal tubules.
OBJECTIVE: To review the cellular and molecular mechanisms of renal repair and recovery after acute kidney injury (AKI). DATA SOURCE: The data were summarized from published research articles. RESULTS: In AKI, there is an acute inflammatory response, epithelial cell necrosis and apoptosis, and shedding of epithelial cells into the tubular lumen. Recent work demonstrates that repopulation of damaged renal tubules occurs primarily from proliferation of tubular epithelial cells and resident renal-specific stem cells, with some contribution of paracrine factors from bone marrow-derived mesenchymal stem cells. In addition, growth factors seem to play a critical role in the repair process in animal models of renal injury. However, attempts to use growth factors in the clinical setting to attenuate human AKI or accelerate renal repair have not yet been successful. The endothelium also plays a critical role in the pathogenesis of AKI. Lastly, in human studies, the effect of dialysis on renal recovery remains poorly understood. CONCLUSIONS: Experimental animal models of AKI demonstrate that renal recovery and repair involves proliferation of tubular epithelial cells and stem cell populations and the coordinated contribution of multiple growth factors. Future efforts to improve recovery from AKI and improve patient outcomes may include novel therapies based on manipulation of populations of stem cells and augmenting repopulation of renal tubules.
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