The hemodynamic and metabolic effects of spironolactone treatment in acute kidney injury assessed by hyperpolarized MRI

Renal ischemia‐reperfusion injury (IRI) is one of the most common types of acute kidney injury. Spironolactone has shown promising kidney protective effects in renal IRI in rats. We investigated the hemodynamic and metabolic effects of spironolactone (100 mg/kg) administered immediately after 40 min unilateral kidney ischemia in rats. Hyperpolarized MRI using co‐polarized [1‐13C]pyruvate and [13C,15N2]urea as well as 1H dynamic contrast‐enhanced (DCE) MRI was performed 24 h after induction of ischemia. We found a significant decrease in renal blood flow (RBF) in the ischemic kidney compared with the contralateral one measured using DCE and [13C,15N2]urea. The RBF measured using [1‐13C]pyruvate and [13C,15N2]urea was significantly altered by spironolactone. The RBFs in the ischemic kidney compared with the contralateral kidney were decreased similarly as measured using both [13C,15N2]urea and [1‐13C]pyruvate in the spironolactone‐treated group. Spironolactone treatment increased the perfusion‐corrected pyruvate metabolism by 54% in both the ischemic and contralateral kidney. Furthermore, we showed a correlation between vascular permeability using a histological Evans blue analysis and the ratio of the volumes of distribution (VoDs), ie VoD‐[13C,15N2]urea/VoD‐[1‐13C]pyruvate. This suggests that [13C,15N2]urea/[1‐13C]pyruvate VoD ratio may be a novel indicator of renal vascular permeability associated with renal damage in rodents. Spironolactone alters the aberrant hemodynamics and metabolism 24 h after ischemia‐reperfusion injury measured using co‐polarized [1‐13C]pyruvate and [13C,15N2]urea. Furthermore, this paper shows that ratios between “volume of distribution” for hyperpolarized [13C,15N2]urea and [1‐13C]pyruvate may be used to indicate vascular leakage in vivo.