Year: 2025
Type: article
Abstract: Nephron loss is a key event during onset and progression of chronic kidney disease, yet the mechanisms dictating tubule repair versus 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 vascular cell adhesion molecule 1 (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. Last, in human kidney transplant biopsies, tubular VCAM1 expression, but not kidney injury molecule 1, 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.
Source: Science Advances
Language: English
Topic: Acute Kidney Injury Research
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,500
Funders: National Science Foundation, Silicon Valley Community Foundation, Alexion Pharmaceuticals, Aarhus Universitet, Aarhus Universitetshospital, Steno Diabetes Center Copenhagen, European Commission, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Aarhus Universitets Forskningsfond, Novo Nordisk, Dansk Nefrologisk Selskab, Augustinus Fonden, Norges Forskningsråd, Vifor Pharma, Letten Foundation
OpenAlex ID: W4415440527