TY - JOUR
T1 - Experimental Aristolochic Acid Nephropathy
T2 - A Relevant Model to Study AKI-to-CKD Transition
AU - Baudoux, Thomas
AU - Jadot, Inès
AU - Declèves, Anne Emilie
AU - Antoine, Marie Hélène
AU - Colet, Jean Marie
AU - Botton, Olivia
AU - De Prez, Eric
AU - Pozdzik, Agnieszka
AU - Husson, Cécile
AU - Caron, Nathalie
AU - Nortier, Joëlle L.
N1 - Publisher Copyright:
Copyright © 2022 Baudoux, Jadot, Declèves, Antoine, Colet, Botton, De Prez, Pozdzik, Husson, Caron and Nortier.
PY - 2022/5/4
Y1 - 2022/5/4
N2 - Aristolochic acid nephropathy (AAN) is a progressive tubulointerstitial nephritis caused by the intake of aristolochic acids (AA) contained in Chinese herbal remedies or contaminated food. AAN is characterized by tubular atrophy and interstitial fibrosis, characterizing advanced kidney disease. It is established that sustained or recurrent acute kidney injury (AKI) episodes contribute to the progression of CKD. Therefore, the study of underlying mechanisms of AA-induced nephrotoxicity could be useful in understanding the complex AKI-to-CKD transition. We developed a translational approach of AKI-to-CKD transition by reproducing human AAN in rodent models. Indeed, in such models, an early phase of acute tubular necrosis was rapidly followed by a massive interstitial recruitment of activated monocytes/macrophages followed by cytotoxic T lymphocytes, resulting in a transient AKI episode. A later chronic phase was then observed with progressive tubular atrophy related to dedifferentiation and necrosis of tubular epithelial cells. The accumulation of vimentin and αSMA-positive cells expressing TGFβ in interstitial areas suggested an increase in resident fibroblasts and their activation into myofibroblasts resulting in collagen deposition and CKD. In addition, we identified 4 major actors in the AKI-to-CKD transition: (1) the tubular epithelial cells, (2) the endothelial cells of the interstitial capillary network, (3) the inflammatory infiltrate, and (4) the myofibroblasts. This review provides the most comprehensive and informative data we were able to collect and examines the pending questions.
AB - Aristolochic acid nephropathy (AAN) is a progressive tubulointerstitial nephritis caused by the intake of aristolochic acids (AA) contained in Chinese herbal remedies or contaminated food. AAN is characterized by tubular atrophy and interstitial fibrosis, characterizing advanced kidney disease. It is established that sustained or recurrent acute kidney injury (AKI) episodes contribute to the progression of CKD. Therefore, the study of underlying mechanisms of AA-induced nephrotoxicity could be useful in understanding the complex AKI-to-CKD transition. We developed a translational approach of AKI-to-CKD transition by reproducing human AAN in rodent models. Indeed, in such models, an early phase of acute tubular necrosis was rapidly followed by a massive interstitial recruitment of activated monocytes/macrophages followed by cytotoxic T lymphocytes, resulting in a transient AKI episode. A later chronic phase was then observed with progressive tubular atrophy related to dedifferentiation and necrosis of tubular epithelial cells. The accumulation of vimentin and αSMA-positive cells expressing TGFβ in interstitial areas suggested an increase in resident fibroblasts and their activation into myofibroblasts resulting in collagen deposition and CKD. In addition, we identified 4 major actors in the AKI-to-CKD transition: (1) the tubular epithelial cells, (2) the endothelial cells of the interstitial capillary network, (3) the inflammatory infiltrate, and (4) the myofibroblasts. This review provides the most comprehensive and informative data we were able to collect and examines the pending questions.
KW - AKI-to-CKD transition
KW - animal models
KW - aristolochic acid nephropathy
KW - aristolochic acids
KW - nephrotoxicants
KW - renal fibrosis
UR - http://www.scopus.com/inward/record.url?scp=85130589658&partnerID=8YFLogxK
U2 - 10.3389/fmed.2022.822870
DO - 10.3389/fmed.2022.822870
M3 - Review article
AN - SCOPUS:85130589658
SN - 2296-858X
VL - 9
JO - Frontiers in Medicine
JF - Frontiers in Medicine
M1 - 822870
ER -