Abstract
Chronic kidney disease (CKD) poses a significant global health burden, necessitating robust animal models for mechanistic studies and drug discovery. Zebrafish offers unique advantages as a powerful models in kidney disease, including high‐throughput compatibility, optical transparency, and significant genetic and nephron homology with both humans and farmed teleosts. However, challenges, such as the species' potent regenerative capacity and a lack of standardized diagnostic thresholds, hinder their broad application. This review systematically summarizes four principal induction strategies: environmental stress, nephrotoxic chemical exposure, CRISPR/Cas‐based gene editing, and transgenesis. We further outline a validation pipeline that integrates functional assays, morphometrics, and histopathology, while advocating for cross‐laboratory harmonization. Additionally, we compare risk factors for CKD and CKD of unknown etiology (CKDu), emphasizing environmental contributors. Collectively, we propose zebrafish as a reproducible platform for aquaculture applications, specifically for nephropathy early‐warning systems and functional feed assessment, and for human therapeutic research. These standardized models hold great promise for high‐throughput drug screening and elucidating disease mechanisms, facilitating the translation of findings to both aquaculture and clinical medicine.