Glomage: A multimodal platform for high-content morphological and RNA profiling of glomeruli in zebrafish and mouse models

Chronic kidney disease affects over 800 million people worldwide, but therapeutic options remain limited. The glomerulus, with its highly specialized podocytes, forms the functional core of blood filtration. However, studying this complex three-dimensional kidney compartment is difficult, which has slowed progress in identifying drugs. Zebrafish larvae are a powerful model for kidney research and drug discovery, but histological staining of individual larvae is time-consuming, and scalable methods for glomerular analysis have been lacking. Here, we establish a high-throughput workflow for isolating, staining, imaging, as well as extracting RNA from hundreds of zebrafish glomeruli simultaneously. The workflow preserves the three-dimensional architecture, enables quantitative assessment of podocyte numbers, and was validated in a podocyte-specific injury model. Moreover, we adapted the protocol for mouse glomeruli, allowing reliable detection of the age-related loss of podocytes. Glomage provides a systematic, cross-species platform for glomerular analysis, opening new opportunities for kidney research and drug discovery.