#427 Not a cluster of grapes, but bananas: cord-like three-dimensional structure of cysts in ADPKD supports tubular obstruction hypothesis

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Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic kidney disease and one of the leading causes of end-stage renal disease. Despite the identification of the causative genes, the pathogenesis of ADPKD remains unclear and hampers the development of effective treatments. The present study aims to elucidate the three-dimensional structure of the kidneys of polycystic kidney disease (PKD) mouse models and its implications for the disease mechanism. Method We performed histological observations on the kidneys of rapid-onset and chronic-onset mouse models of PKD, and also transparentized the kidneys for three-dimensional imaging. Results We discovered that the cysts had a cord-like three-dimensional structure resembling a cluster of bananas rather than a bunch of grapes, suggesting tubular obstruction as the initiating event. Furthermore, the presence of epithelial cell bridges within the renal tubules, as observed in both three-dimensional images and two-dimensional pathological sections, was identified as a potential causative factor for the obstruction. In addition, a comparative analysis of Ki67 staining in kidney tissue at various developmental stages was conducted with wild type mice. This analysis revealed no significant differences, suggesting that there was no additional cell proliferation. Conclusion The findings of this study provide robust support for the obstruction hypothesis and significantly challenge the proliferation hypothesis for ADPKD. These results offer novel insights that could lead to the development of more effective treatment strategies.

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