Li, J. J. X.; Teoh, J. Y. C.; Lai, H. M.

We revisit the assumption that the human glomerulus consists of a capillary network with one afferent arteriole and only one efferent arteriole. Using three-dimensional tissue imaging, we unambiguously demonstrate the existence of multiple efferent arterioles via total reconstruction of a full human glomerular capillary network. Through graph network analysis, we found these multiple efferent arterioles can be topologically distinct or equivalent with reference to the global glomerular capillary network, and were strategically positioned with respect to the afferent arteriole. We also found the extraglomerular connections between two efferent arterioles may have significant contributions to the redistribution of intraglomerular blood flow. These new findings can provide new paradigms in the regulation and dysfunction of glomerular ultrafiltration, the crosstalk between intra- and extraglomerular factors, and the cross-coupling between nephrons.