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

Abstract

We investigated the three-dimensional structure of the kidneys of mouse models of autosomal dominant polycystic kidney disease (ADPKD), a progressive genetic kidney disease and one of the leading causes of end-stage renal disease. We performed histological observations and transparentized the kidneys for three-dimensional imaging on rapid-onset and chronic-onset models. We found that the cysts had a cord-like structure resembling a cluster of bananas rather than a bunch of grapes, suggesting tubular obstruction as the initiating event. We also detected epithelial cell bridges within the renal tubules, which could be the cause of the obstruction. We compared the cell proliferation of kidney tissue at different developmental stages with wild type mice, and found no significant difference, indicating that there was no additional cell proliferation. Our findings support the obstruction hypothesis and challenge the proliferation hypothesis for ADPKD, and may provide new insights for finding potential treatments.