Spatiotemporal ATP Dynamics during AKI Predict Renal Prognosis

Area of Science:

• Cell biology
• Renal physiology
• Biomedical imaging

Background:

• Adenosine triphosphate (ATP) depletion in renal tubular cells is central to kidney disease pathogenesis.
• Lack of methods to visualize *in vivo* ATP dynamics has limited research.
• Understanding ATP dynamics is crucial for developing kidney disease treatments.

Purpose of the Study:

• To develop and utilize a novel mouse model for visualizing spatiotemporal ATP dynamics in renal tubular cells during ischemic reperfusion (IR) injury.
• To assess the correlation between acute-phase ATP recovery and chronic-phase kidney fibrosis.
• To evaluate the protective effect of hypothermia on kidney tissue during IR injury.

Main Methods:

• Generated a novel mouse line expressing an ATP biosensor for *in vivo* ATP visualization.
• Employed two-photon microscopy to observe single-cell ATP dynamics during warm and cold IR.
• Quantified kidney fibrosis 2 weeks post-IR and correlated it with ATP recovery patterns.

Main Results:

• Proximal tubule (PT) cells exhibited rapid ATP depletion and slower recovery compared to distal tubule (DT) cells.
• PT ATP recovery kinetics inversely correlated with the extent of fibrosis.
• Hypothermia during ischemia led to faster ATP recovery and reduced fibrosis, demonstrating a protective effect.

Conclusions:

• *In vivo* visualization of ATP dynamics reveals differential sensitivity of PT and DT cells to ischemic injury.
• PT ATP recovery patterns in acute kidney injury (AKI) may serve as prognostic indicators for fibrosis.
• Hypothermia is a potential therapeutic strategy for mitigating IR-induced kidney damage.