Elastin imaging enables noninvasive staging and treatment monitoring of kidney fibrosis

Fibrosisis the common endpoint and currently the best predictor of progression of chronic kidney diseases (CKDs). Despite several drawbacks, biopsies remain the only available means to specifically assess the extent of renal fibrosis. Here, we show that molecular imagingof the extracellular matrix protein elastinallows for noninvasive staging and longitudinal monitoring of renal fibrosis. Elastinwas hardly expressed in healthy mouse, rat, and human kidneys, whereas it was highly up-regulated in cortical, medullar, and perivascular regions in progressive CKD. Compared to a clinically relevant control contrast agent, the elastin-specific magnetic resonance imaging agentESMA specifically detected elastinexpression in multiple mouse models of renal fibrosisand also in fibrotic human kidneys. Elastinimaging allowed for repetitive and reproducible assessment of renal fibrosis, and it enabled longitudinal monitoring of therapeutic interventions, accurately capturing anti-fibrotic therapy effects. Last, in a model of reversible renal injury, elastinimaging detected ensuing fibrosisnot identifiable via routine assessment of kidney function. Elastinimaging thus has the potential to become a noninvasive, specific imaging method to assess renal fibrosis.