Scintigraphy precisely detects differential recovery of glomerular and tubular function following renal ischemia-reperfusion injury

Objectives The murine model of renal ischemia-reperfusion injury (IRI) is widely used used for pathophysiological and therapeutic studies in preclinical research. Although glomeruli are known to be more resistant to acute ischemia than tubules, renal function is generally monitored based on glomerular filtration function. This study examines differential characteristics of glomerular and tubular function after renal IRI during follow-up examination.

Methods Renal glomerular and tubular function were evaluated 2, 4, 8, and 18 days following a warm ischemia of 45 min in a murine model of IRI using 99mTc-DTPA and 99mTc-MAG3 scintigraphy, respectively. Additional histological analysis was performed.

Results IRI led to significant reduction of glomerular filtration function with a minimum in peak (56.8%±11.1%;p<0.05) and filtration rate (39.9%±8.1%;p<0.05) on day 4, as assessed by 99mTc-DTPA scintigraphy. Compared to baseline, full recovery of glomerular function peak (99.3%±6.1%;n.s.) and filtration rate (85.2%±7.9%;n.s.) was recorded by day 18. In contrast, 99mTc-MAG3 imaging detected impairment of tubular function peak (74.0%±4.6%;p<0.05) and excretion rate (35.6%±4.1%;p<0.05) already on day 2 without evidence for recovery of tubular function peak (61.4%±12.8%;p<0.05) and excretion rate (47.3%±13.4%;p<0.05) 18 days post ischemia. Histological analysis was marked by considerable tubular atrophy/ necrosis. Glomeruli showed excellent vitality with normal size and no signs of destruction.

Conclusions Specific determination of glomerular filtration and tubular excretion function using 99mTc-DTPA and 99mTc-MAG3 scintigraphy enables the detection of differential functional recovery of glomeruli and tubules following renal IRI. These findings may aid researchers with the selection of the appropriate markers for monitoring renal function in experimental models.

Research Support This work was supported by the Else Kröner-Fresenius-Foundation