Charting the course of renal cryoinjury

We sought to characterize a minor renal cryoinjury that allows investigation into renal damage processes and subsequent endogenous repair mechanisms. To achieve this, we induced a small cryoinjury to mice, in which the transient superficial application of a liquid nitrogen‐cooled cryoprobe to the exposed kidney induces a localized lesion that did not impair renal function. The resulting cryoinjury was examined by immunohistochemistry and Laser‐Doppler flowmetry. Within hours of cryoinjury induction, tubular and vascular necrotic damage was observed, while blood flow in the directly injured area was reduced by 65%. The injured area demonstrated a peak in tubular and perivascular cell proliferation at 4 days postinjury, while apoptosis and fibrosis peaked at day 7. Infiltration of macrophages into the injury was first observed at day 4, and peaked at day 7. Vascular density in the direct injured area was lowest at day 7. As compared to the direct injured area, the (peripheral) penumbral region surrounding the directly injured area demonstrated enhanced cellular proliferation (2.5–6‐fold greater), vascular density (1.6–2.9 fold greater) and blood perfusion (twofold greater). After 4 weeks, the area of damage was reduced by 73%, fibrosis decreased by 50% and blood flow in the direct injured area was reestablished by 63% with almost complete perfusion restoration in the injury's penumbral region. In conclusion, kidney cryoinjury provides a flexible facile model for the study of renal damage and associated endogenous repair processes. We have examined a minor kidney cryoinjury that allows investigation into renal damage processes and subsequent repair mechanisms. The initial injury is characterized by necrosis, apoptosis, cell proliferation, reduced blood perfusion, macrophage infiltration and fibrosis. However, at 4‐weeks postinjury, the injury lesion was reduced by 73% in size with reduced fibrosis, while blood flow was almost completely restored.