99mTc-MAG3 scintigraphy for the longitudinal follow-up of kidney function in a mouse model of renal ischemia-reperfusion injury

Unilateral warm ischemia was induced in scid beige mice by vascular clamping of the kidney hilum for 40 min. 99mTc-MAG3 scintigraphy was performed prior to injury, 8 and 14 days post ischemia. The fractional uptake rate [FUR] was calculated from scintigraphy data as a measure of renal clearance.FUR demonstrated a significant functional impairment of the ischemic kidney 8 and 14 days after injury (P < 0.05 vs. baseline), while contralateral non-ischemic kidneys showed no significant changes. In histological analysis, ischemic kidneys exhibited tubular dilatation and cytoplasmic degeneration as signs of hypoxia without any evidence for necrosis.FUR enables the detection of renal dysfunction and longitudinal long-term follow-up examination in the same individual. Our model may facilitate preclinical therapy evaluation for the identification of effective renoprotective therapies.Following kidney transplantation, renal ischemia-reperfusion injury contributes to allograft dysfunction and loss. Promising experimental results have failed to translate into therapies for clinical use. This may be partly explained by methodological limitations in the experimental setting. In the preclinical model of renal ischemia-reperfusion injury, functional data based on standard biochemical parameters can only be obtained in the acute phase of injury [1,2]. Specifically, serum creatinine levels were shown to represent a valid indicator of renal dysfunction only during the early post-ischemic period of 24 to 72 h [3].Dynamic scintigraphy using the radioactive compound technetium-99m-mercapto-acetyl-tri-glycine [99mTc-MAG3] was recently introduced as a technique for the determination of early functional changes in a murine model of renal ischemia-reperfusion injury [4]. The aim of the present study was to apply 99mTc-MAG3 imaging for longitudinal follow-up studies of early and, most importantly, long-term kidney function after injury. The fractional uptake rate [FUR] was calculated in analo