Experimental Aristolochic Acid Nephropathy: A Relevant Model to Study AKI-to-CKD Transition

Area of Science:

• Nephrology
• Toxicology
• Pathology

Background:

• Aristolochic acid nephropathy (AAN) is a severe kidney disease linked to aristolochic acids (AA) in traditional remedies and food.
• Acute kidney injury (AKI) episodes are known contributors to chronic kidney disease (CKD) progression.
• Understanding AA-induced nephrotoxicity mechanisms can illuminate the AKI-to-CKD transition.

Purpose of the Study:

• To develop a translational rodent model of AAN to study the AKI-to-CKD transition.
• To identify the cellular and molecular mechanisms driving AA-induced kidney damage and disease progression.

Main Methods:

• Reproduced human AAN in rodent models to mimic the AKI-to-CKD transition.
• Analyzed cellular infiltration, tubular changes, and interstitial fibrosis.
• Investigated the roles of tubular epithelial cells, endothelial cells, inflammatory cells, and myofibroblasts.

Main Results:

• The model exhibited an early AKI phase with acute tubular necrosis, followed by inflammatory cell infiltration.
• A chronic phase showed progressive tubular atrophy, dedifferentiation, and necrosis of tubular epithelial cells.
• Increased vimentin and αSMA-positive cells expressing TGFβ indicated fibroblast activation and collagen deposition, leading to CKD.

Conclusions:

• Identified four key cellular components in the AKI-to-CKD transition: tubular epithelial cells, interstitial endothelial cells, inflammatory infiltrate, and myofibroblasts.
• The rodent model effectively replicates human AAN and provides insights into AKI-to-CKD progression.
• Further research is needed to address pending questions regarding AA-induced nephrotoxicity and CKD development.