In vivo longitudinal two-photon intravital kidney imaging of a dynamic DHA crystal formation and tubular deterioration in the adenine-induced chronic kidney disease mouse model

Chronic kidney disease (CKD) is one of the most prevalent kidney disorders with no distinct symptoms and gradual loss of kidney function over time. The underlying mechanism in the pathogenesis of CKD with various causes such as high blood pressure, diabetes, high cholesterol, and kidney infection is not well understood. Following up on the pathophysiological alterations, longitudinal in vivo cellular-level imaging during CKD progression can provide unique insights and valuable information for diagnosing and managing CKD. In this study, with two-photon kidney intravital imaging, we achieved a repetitive longitudinal visualization of the kidney in an adenine diet-induced CKD mouse model over 30 days. Interestingly, based on a second-harmonics generation signal, we clearly visualized and quantified the formation of 2,8-dihydroxyadenine (DHA) crystals over time in a label-free manner. The imaging results were well correlated with CKD progression monitored by a standard blood test of blood urea nitrogen (BUN) and cystatin C levels. This result suggests the potential of the label-free second-harmonics generation crystal imaging as a novel optical technique for in vivo CKD progression monitoring.