Twin Glomeruli: a Newly Discovered Marker of Neonephrogenesis in the Ischemia-Reperfusion Injured Adult Mouse Kidney

The renal glomerulus, a capillary network between two arterioles, is essential for urine production in mammals. While it partially regenerates after renal injury, its precise mechanisms remain unclear, and stereological studies on post-injury glomerular structural changes are limited.

Therefore, this study aims to investigate three-dimensional glomerular alterations over time following ischemia-reperfusion injury (IRI) in adult mouse kidneys. Synchrotron radiation micro-computed tomography (SR-MCT) and immunohistochemical analyses were employed to visualize and quantify three-dimensional glomerular structures and nephron numbers from 1 to 21 days post-IRI.

A unique "twin glomeruli" structure, linked to three arterioles through an atypical "aefferent" arteriole, appeared between 3 and 21 days post-IRI, peaked on day 9, and exhibited features distinct from both degenerating and developing glomeruli. SR-MCT revealed a time-dependent increase in nephron numbers between 1 and 21 days post-IRI, while immunohistochemistry revealed significant elevated glomerular and tubular densities from days 9 to 21. These findings suggest that twin glomeruli are transient structures induced by IRI and may contribute to nephron expansion.

This study challenges current understanding by demonstrating that twin glomeruli represent an atypical glomerular structure occurring during kidney repair and suggesting possible neonephrogenesis in the adult mouse kidney, a phenomenon previously considered impossible after birth. If similar results are observed in humans, it could lead to significant changes in the approaches and objectives for treating renal diseases. Additionally, a comprehensive investigation into the numerical response of glomerular counts to various stimuli could provide valuable insights into kidney regeneration and repair.