In vivo expression of VCAM1 precedes nephron loss following kidney tubular necrosis

Nephron loss is a key event during the onset and progression of chronic
kidney disease, yet the mechanisms determining whether tubules undergo
successful repair or progress to atrophy remain poorly understood. While
fibrosis has been proposed to drive progressive organ damage, antifibrotic
therapies have failed in clinical trials. Here, we reveal that tubular
VCAM1-expression precedes nephron loss, fibrosis, and long-term kidney
dysfunction. Using serial intravital microscopy in transgenic mice, we
track tubulointerstitial remodeling between injured and intact tissue over
3 weeks. VCAM1 is rapidly induced in a distinct subset of injured tubules,
preceding atrophy with sustained fibroblast recruitment. However,
fibroblasts remain confined to injury sites and do not cause secondary
damage in uninjured tubules. Finally, in human kidney transplant biopsies,
tubular VCAM1 expression - but not KIM1 - correlates negatively with early
and 12-month graft function, underscoring its potential as a biomarker of
adverse outcomes. These findings position VCAM1 as an early indicator of
tubular fate and nephron loss.