Determinations of renal cortical and medullary oxygenation using blood oxygen level-dependent magnetic resonance imaging and selective diuretics

Abstract

Objective: This study was undertaken to test the hypothesis that blood O2 level-dependent magnetic resonance imaging (BOLD MRI) can detect changes in cortical proximal tubule (PT) and medullary thick ascending limb of Henle (TAL) oxygenation consequent to successive administration of furosemide and acetazolamide (Az). Assessment of PT and TAL function could be useful to monitor renal disease states in vivo. Therefore, the adjunct use of diuretics that inhibit Na reabsorption selectively in PT and TAL, Az and furosemide, respectively, may help discern tubular function by using BOLD MRI to detect changes in tissue oxygenation.

Material and methods: BOLD MRI signal R2* (inversely related to oxygenation) and tissue oxygenation with intrarenal O2 probes were measured in pigs that received either furosemide (0.05 mg/kg) or Az (15 mg/kg) alone, Az sequentially after furosemide (n = 6 each, 15-minute intervals), or only saline vehicle (n = 3).

Results: R2* decreased in the cortex of Az-treated and medulla of furosemide-treated kidneys, corresponding to an increase in their tissue O2 assessed with probes. However, BOLD MRI also showed decreased cortical R2* following furosemide that was additive to the Az-induced decrease. Az administration, both alone and after furosemide, also decreased renal blood flow (-26% ± 3.5% and -29.2% ± 3%, respectively, P < 0.01).

Conclusion: These results suggest that an increase in medullary and cortical tissue O2 elicited by selective diuretics is detectable by BOLD MRI, but may be complicated by hemodynamic effects of the drugs. Therefore, the BOLD MRI signal may reflect functional changes additional to oxygenation, and needs to be interpreted cautiously.

Figures

Figure 1

Schematic of the experimental design, consisting of two experimental periods following a baseline period. Furosemide was administered in period 1 to furosemide (furo) treated groups, acetazolamide (az) was administered in period 2 and control groups were administered saline (s) in place of either or both furosemide or acetazolamide.

Figure 2

Coronal image (A) with slice locations indicated with solid lines, the inset axial-oblique image distinguishes cortex (solid line) and medulla (dashed line) regions of interest (ROI). Histological staining with hematoxylin and eosin (×5) showing the path and insertion point of the probe in the cortex (B) and medulla, with inset 20× zoom (C).

Figure 3

Change from baseline in R2* in the cortex (A) and medulla (B) of experimental groups that received either saline (s) vehicle (s+s and s+az) or furosemide (furo) (furo+s and furo+az) in period 1, and vehicle (s+s and furo+s) or acetazolamide (az) (s+az and furo+az) in period 2. * p

Figure 4

Change from baseline in tissue O2 in the renal cortex (A) and medulla (B) of experimental groups that received either saline (s) vehicle (s+s and s+az) or furosemide (furo) (furo+s and furo+az) in period 1, and vehicle (s+s and furo+s) or acetazolamide (az) (s+az and furo+az) in period 2. * p

Figure 5

Change from baseline in renal blood flow (RBF) during administration of saline (s), furosemide (furo), and/or acetazolamide (az). Experimental groups that received az showed a decrease in RBF. *p