Published online before print April 10, 2008, 10.1148/radiol.2473070877
(Radiology 2008;247:754-761.)
© RSNA, 2008
Renal Oxygenation Changes during Acute Unilateral Ureteral Obstruction: Assessment with Blood Oxygen Level–Dependent MR Imaging—Initial Experience1
Harriet C. Thoeny, MD,
Thomas M. Kessler, MD,
Sonia Simon-Zoula, PhD,
Frederik De Keyzer, MSc,
Markus Mohaupt, MD,
Urs E. Studer, MD, and
Peter Vermathen, PhD
1 From the Department of Radiology, Neuroradiology and Nuclear Medicine (H.C.T., S.S.), Department of Urology (T.M.K., U.E.S.), Department of Nephrology and Hypertension (M.M.), and Department of Clinical Research (P.V.), University Hospital of Bern, Inselspital, Freiburgstrasse 10, CH-3010 Bern, Switzerland; and Department of Radiology, University Hospitals of Leuven, Leuven, Belgium (F.D.K.). Received May 22, 2007; revision requested July 24; revision received August 17; accepted September 12; final version accepted November 1. H.C.T. supported by a research grant from the Swiss National Foundation, National Center of Competence in Research, "Computer-aided and image-guided medical interventions," NCCR CO-ME, and a grant from the H.E.M. Foundation, Liechtenstein.
Address correspondence to H.C.T. (e-mail: Harriet.Thoeny{at}insel.ch).
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ABSTRACT
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Purpose: To prospectively determine if changes in intrarenal oxygenation during acute unilateral ureteral obstruction can be depicted with blood oxygen level–dependent (BOLD) magnetic resonance (MR) imaging.
Materials and Methods: The study was approved by the local ethics committee, and written informed consent was obtained from all patients. BOLD MR imaging was performed in 10 male patients (mean age, 45 years ± 17 [standard deviation]; range, 20–73 years) with a distal unilateral ureteral calculus and in 10 healthy age-matched male volunteers to estimate R2*, which is inversely related to tissue Po2. R2* values were determined in the cortex and medulla of the obstructed and the contralateral nonobstructed kidneys. To reduce external effects on R2*, the R2* ratio between the medulla and cortex was also analyzed. Statistical analysis was performed with nonparametric rank tests. P < .05 was considered to indicate a significant difference.
Results: All patients had significantly lower medullary and cortical R2* values in the obstructed kidney (median R2* in medulla, 10.9 sec–1 [range, 9.1–14.3 sec–1]; median R2* in cortex, 10.4 sec–1 [range, 9.7–11.3 sec–1]) than in the nonobstructed kidney (median R2* in medulla, 17.2 sec–1 [range, 14.6–23.2 sec–1], P = .005; median R2* in cortex, 11.7 sec–1 [range, 11.0–14.0 sec–1], P = .005); values in the obstructed kidneys were also significantly lower than values in the kidneys of healthy control subjects (median R2* in medulla, 16.1 sec–1 [range, 13.9–18.1 sec–1], P < .001; median R2* in cortex, 11.6 sec–1 [range, 10.5–12.9 sec–1], P < .001). R2* ratios in the obstructed kidneys (median, 1.06; range, 0.85–1.27) were significantly lower than those in the nonobstructed kidneys (median, 1.49; range, 1.26–1.71; P = .005) and those in the kidneys of healthy control subjects (median, 1.38; range, 1.23–1.47; P < .001). In contrast, R2* ratios in the nonobstructed kidneys of patients were significantly higher than those in kidneys of healthy control subjects (P = .01).
Conclusion: Increased oxygen content in the renal cortex and medulla occurs with acute unilateral ureteral obstruction, suggesting reduced function of the affected kidney.
© RSNA, 2008
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INTRODUCTION
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Acute unilateral ureteral obstruction due to renal stones is a frequent event, affecting 5%–15% of the population worldwide (1). During obstruction, functional and biochemical alterations occur in the kidney. Partial chronic obstruction can lead to chronic renal insufficiency, whereas an immediate onset of acute obstruction can result in acute renal failure in solitary kidneys. Therefore, early and accurate diagnosis and prompt implementation of appropriate treatment strategies are of utmost importance in preserving or restoring renal function (2).
Blood oxygen level–dependent (BOLD) magnetic resonance (MR) imaging results provide an estimate for the partial pressure of oxygen (Po2) in tissue, assuming that all other factors—such as shimming status and measurement parameters—are kept constant (3,4). In the mid-1990s, BOLD MR imaging was applied to study intrarenal oxygenation noninvasively (4). The apparent spin-spin relaxation rate R2* (1/T2*) acquired with BOLD MR imaging is related to the tissue content of paramagnetic deoxyhemoglobin, which in turn is negatively related to the partial pressure of oxygen within the blood (4).
The feasibility and reproducibility of the BOLD technique has been demonstrated in kidneys of healthy volunteers as well as in renal allografts (4–6). Furthermore, as evidenced by BOLD MR imaging results, water diuresis has been found to induce an increase in medullary oxygenation in control subjects but not in patients with diabetes, suggesting impairment of adaptive vasodilatation within the renal medulla in diabetes (7). These findings have been confirmed in experimental settings in studies performed in diabetic rats (8,9). BOLD MR imaging of human kidney transplants (10) showed significantly lower R2* in eight patients with acute allograft rejection than in six patients with normally functioning kidney transplants and six patients with acute tubular necrosis. In patients with chronic allograft nephropathy, BOLD MR imaging has demonstrated significant changes in medullary and cortical bioavailability (11).
In an experimental study in eight pigs, BOLD MR imaging was able to depict changes in intrarenal oxygenation during an acute reduction of renal blood flow following occlusion of the renal artery (12). In another study performed in three pigs (13), oxygenation as assessed with BOLD MR imaging was reduced in the cortex and increased in the medulla (both ipsilaterally and contralaterally) 24 hours after unilateral ureteral obstruction. These BOLD MR imaging findings were validated by using oxygen-sensitive microelectrodes inserted in the cortex and medulla of pig kidneys (13). Cortical and medullary R2* levels were reported to correlate linearly with renal tissue Po2 levels (13). On the basis of the findings of these animal studies, the aim of our study was to prospectively determine if changes in intrarenal oxygenation during acute unilateral ureteral obstruction can be depicted with BOLD MR imaging.
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MATERIALS AND METHODS
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Study Participants
The study protocol was approved by the local ethics committee of the Kanton Bern, and written informed consent was obtained from all patients and volunteers.
A randomly selected series of 10 male patients (mean age, 45 years ± 17 [standard deviation]; age range, 20–73 years) who were referred to the emergency department because of acute flank pain were included. All patients had a distal ureteral calculus diagnosed at unenhanced helical computed tomography (CT). The median time between the start of symptoms and the MR imaging study was 25 hours (range, 5–47 hours). All MR imaging studies were performed before stone treatment. Patients were included only if the MR imaging unit was available in a reasonable time period before stone treatment so as not to delay treatment.
After admittance to the emergency department, patients immediately received standard treatment measures against colic (the administration of metamizol, nonsteroidal antiinflammatory drugs [NSAIDs], morphine derivates). Excessive rehydration of the patients was avoided to prevent fornix rupture of the obstructed kidney, but we were therefore unable to completely standardize the hydration state of our study population. The serum creatinine level at admission was within the normal range (<105 µmol/L) in all but two patients, who had slightly increased values of 118 and 116 µmol/L. After diagnosis of a distal ureteral calculus at unenhanced helical CT, the MR imaging examination was performed as soon as possible.
A total of five patients were initially treated with extracorporeal shock wave lithotripsy, which was successful in four. In one patient, ureterorenoscopic stone extraction was required. Three patients experienced ureteral stone passage after medical treatment with 100 mg per day of an NSAID (diclofenac, Voltaren Retard; Novartis Pharma, Bern, Switzerland) and 400 µg per day of an 
-blocking agent (tamsulosin, Pradif T; Boehringer Ingelheim, Basel, Switzerland), and in one patient, a double-J catheter was placed. The remaining patient required percutaneous nephrostomy because of obstructive pyelonephritis. After 2 weeks of antibiotic treatment, ureterorenoscopic stone extraction was performed.
A group of 10 age-matched healthy male volunteers (mean age, 45 years ± 14; age range, 23–64 years) who had no history of renal disease, hypertension, or other vascular diseases and who were not taking any medications underwent the same MR imaging protocol. All control subjects had normal serum creatinine levels and showed no morphologic abnormalities in both kidneys at conventional MR imaging.
MR Imaging
MR imaging was performed with a 1.5T MR imaging unit (Sonata; Siemens, Erlangen, Germany) with a 40 mT/m maximum gradient capability by using combined anterior and posterior six-channel body coils. For morphologic evaluation, a coronal T2-weighted half-Fourier rapid acquisition with relaxation enhancement sequence was performed, as well as axial and coronal T1-weighted fast low-angle shot gradient-echo sequences. For functional evaluation, BOLD MR imaging was performed by using a multiple gradientrecalled echo sequence. Five to six coronal sections were acquired with section thicknesses of 5 mm and an intersection gap of 1 mm. Field of view and matrix size were 400 x 400 mm2 and 256 x 256, respectively, and one signal was acquired. Other parameters were as follows: repetition time msec/echo time msec, 65/6–52; interecho spacing time, 4.2 msec; flip angle, 30°; and bandwidth, 325 Hz/pixel. Twelve T2*-weighted images, corresponding to 12 different echoes, were acquired for each section within a single breath hold of 17 seconds. The maximal imaging time per patient was 15 minutes. An example BOLD MR image is shown in Fig 1.
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Figure 1a: (a) Coronal BOLD MR image (multiple gradient-recalled echo sequence, 65/6) and (b) corresponding calculated R2* image of obstructed right (arrows) and nonobstructed left (arrowheads) kidneys in an individual patient. In b, corticomedullary differentiation is reduced in the obstructed kidney compared with the contralateral kidney.
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Figure 1b: (a) Coronal BOLD MR image (multiple gradient-recalled echo sequence, 65/6) and (b) corresponding calculated R2* image of obstructed right (arrows) and nonobstructed left (arrowheads) kidneys in an individual patient. In b, corticomedullary differentiation is reduced in the obstructed kidney compared with the contralateral kidney.
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Image Analysis
The data were evaluated at an independent workstation. Postprocessing was performed by using a software program created in-house (Interactive Data Language; RSI, Boulder, Colo).
Morphologic evaluation.—The locations and sizes of the stones were assessed with CT. Perirenal stranding (classified on a scale of 1–3 as absent, moderate, or marked), fornix rupture (classified as absent or present), and dilatation of the collecting system (classified on a scale of 1–4 as none, mild, moderate, or pronounced) of the affected kidney as seen on MR images were evaluated (H.C.T., with 10 years of experience in urologic MR imaging). Furthermore, corticomedullary differentiation (normal, reduced, or absent) and the presence of focal lesions were analyzed in both kidneys.
Functional evaluation.—All images displayed adequate signal-to-noise ratio and did not show substantial artifacts, so all measurements were included in the analysis.
BOLD MR imaging.—R2* (1/T2*) maps were calculated on a pixel-by-pixel basis by fitting the signal intensity ln (Si) versus the echo time (TEi) to a (weighted) linear function.
The readers were blinded to clinical information regarding the side of obstruction. Circular regions of interest (ROIs) were delineated in the cortex and medulla on several BOLD MR images obtained with a 6-msec echo time and on corresponding coronal T1-weighted images of each kidney by two observers in consensus (H.C.T., with 10 years of experience in renal MR imaging and BOLD imaging, and S.S., with 4 years of experience). Thereafter, the individual ROIs were merged for each kidney separately for the cortex and the medulla, yielding a total of four ROIs for each patient (mean number of ROIs, 37 ± 8 for both the cortex and the medulla; mean individual ROI size, 0.26 cm3 ± 0.02 and 0.29 cm3 ± 0.02 for cortex and medulla, respectively). R2* values can be substantially influenced by external effects such as magnetic field inhomogeneity or the physiologic status of the subject (13–15). Therefore, the R2* ratio between the medulla and cortex was also analyzed, assuming that in first approximation, R2* values in the cortex and medulla are similarly affected by external influences such that their impact is reduced in the corticomedullary ratio. Also, the difference in R2* between the cortex and medulla was analyzed; these results, however, are not presented because they were similar to those for the R2* ratio.
The same procedure was used to evaluate the kidneys of the healthy volunteers. R2* values in the cortex and medulla for healthy volunteers were first calculated for the right and left kidneys separately. Between these separate right and left kidney values, no significant difference could be found, and mean R2* values were then calculated for cortex and medulla by averaging right and left R2* values.
Statistical Analysis
The sample size of 10 patients and 10 matched control subjects (healthy volunteers) was based on results of a power analysis that was in turn based on previous BOLD MR imaging findings in native kidneys (6) and that assumed a similar standard deviation. In these conditions, an R2* difference of 1.1 sec–1 in the medulla and 0.5 sec–1 in the cortex within subjects and 1.5 sec–1 in the medulla and 0.7 sec–1 in the cortex between subjects can be detected with 10 subjects at a significance level of .05 and 80% statistical power. Considering the relatively large changes found in animal studies (13) after unilateral ureteral obstruction, these calculated values can be presumed to be lower than the anticipated R2* differences, and the calculated detectable differences may be required in general for BOLD MR imaging measurements to be clinically relevant in urinary stone disease.
Statistical analysis was performed by using nonparametric rank tests: the Wilcoxon signed rank test for paired samples to compare data in the obstructed with those in the contralateral nonobstructed kidneys and the Mann-Whitney U test for unpaired samples to compare data in patients with data in healthy control subjects. Pearson linear regression analysis was used to compare R2* values in the obstructed kidneys with morphologic findings (by using the classifications for dilatation of the collecting system and perirenal stranding) and with clinical findings (time after onset of symptoms). For all statistical tests, P < .05 was considered to indicate a statistically significant difference. Statistical analysis was performed with software (SPSS, version 12.0.1, SPSS, Chicago, Ill; and Excel 2002, Microsoft, Redmond, Wash).
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RESULTS
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Morphologic Evaluation
All stones were located in the distal ureter (two on the right side, eight on the left side) (Table 1). The median size was 3 mm (range, 3–10 mm).
Perirenal stranding was observed in eight obstructed kidneys (stranding was moderate in seven and marked in one kidney) and was absent in two. Fornix rupture was observed in one of 10 kidneys. Dilatation of the collecting system was noted in nine kidneys (dilatation was mild in one kidney, moderate in seven, and pronounced in one). Corticomedullary differentiation was normal in all patients. Focal lesions (cortical cysts) were observed in one patient.
Functional Evaluation
R2* values were significantly lower in the medullas of the patients' obstructed kidneys (median R2*, 10.9 sec–1; range, 9.1–14.3 sec–1) than in the medullas of the contralateral nonobstructed kidneys (median R2*, 17.2 sec–1; range, 14.6–23.2 sec–1; P = .005) and the medullas of the kidneys of healthy control subjects (median R2*, 16.1 sec–1; range, 13.9–18.1 sec–1; P < .001) (Table 2, Fig 1). Also, in the cortex, R2* was significantly lower in the obstructed kidney (median R2*, 10.4 sec–1; range, 9.7–11.3 sec–1) than in the contralateral nonobstructed kidney (median R2*, 11.7 sec–1; range, 11.0–14.0 sec–1; P = .005 [Table 2]) and the kidneys of healthy control subjects (median R2*, 11.6 sec–1; range, 10.5–12.9 sec–1; P < .001 [Fig 2]). The R2* ratio between the medulla and cortex in the obstructed kidney (median, 1.06; range, 0.85–1.27) was significantly lower than that in the contralateral nonobstructed kidney (median, 1.49; range, 1.26–1.71; P = .005 [Fig 2]) and that in the kidneys of healthy control subjects (median, 1.38; range, 1.23–1.47; P < .001 [Fig 2]).
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Figure 2a: Box plots of (a) R2* in medulla, (b) R2* in cortex, and (c) R2* ratio in obstructed and contralateral nonobstructed patient kidneys and kidneys of healthy control subjects. For each group, the box plot indicates the median (central horizontal line), the 75th quartile (top of box), the 25th quartile (bottom of box), extreme values (*,  ), and the smallest and largest nonextreme values (whiskers). Medullary and cortical R2* values and R2* ratios in the obstructed kidneys were significantly lower than those in the contralateral nonobstructed kidneys and the kidneys of healthy control subjects. R2* ratios in the nonobstructed kidneys of patients were significantly higher than those in the kidneys of healthy control subjects.
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Figure 2b: Box plots of (a) R2* in medulla, (b) R2* in cortex, and (c) R2* ratio in obstructed and contralateral nonobstructed patient kidneys and kidneys of healthy control subjects. For each group, the box plot indicates the median (central horizontal line), the 75th quartile (top of box), the 25th quartile (bottom of box), extreme values (*, ), and the smallest and largest nonextreme values (whiskers). Medullary and cortical R2* values and R2* ratios in the obstructed kidneys were significantly lower than those in the contralateral nonobstructed kidneys and the kidneys of healthy control subjects. R2* ratios in the nonobstructed kidneys of patients were significantly higher than those in the kidneys of healthy control subjects.
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Figure 2c: Box plots of (a) R2* in medulla, (b) R2* in cortex, and (c) R2* ratio in obstructed and contralateral nonobstructed patient kidneys and kidneys of healthy control subjects. For each group, the box plot indicates the median (central horizontal line), the 75th quartile (top of box), the 25th quartile (bottom of box), extreme values (*, ), and the smallest and largest nonextreme values (whiskers). Medullary and cortical R2* values and R2* ratios in the obstructed kidneys were significantly lower than those in the contralateral nonobstructed kidneys and the kidneys of healthy control subjects. R2* ratios in the nonobstructed kidneys of patients were significantly higher than those in the kidneys of healthy control subjects.
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No significant differences in R2* between the nonobstructed kidneys and the kidneys of healthy control subjects were observed in the cortex and medulla, although R2* in the nonobstructed medulla of patients showed a trend toward higher values (P = .054). However, the R2* ratio in the nonobstructed kidneys of patients was significantly higher than that in the kidneys of healthy control subjects (P = .01).
Comparison of Results of Morphologic, Clinical, and Functional Evaluation
In the medullas of the obstructed kidneys, R2* (r = –0.73, P < .02) and R2* ratio (r = –0.77, P < .008) decreased with increasing severity of perirenal stranding (Fig 3a, 3b). No significant correlation between R2* or R2* ratio and dilatation of the collecting system was detected. Substantially lower medullary R2* values (r = –0.66, P = .10) and R2* ratios (r = –0.71, P = .055) were measured with increasing time since onset of clinical symptoms (Fig 3c, 3d), with one apparently outlying subject (who was, however, not excluded from the analysis).
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Figure 3a: Graphs show relationships of (a) medullary R2* in obstructed kidneys and perirenal stranding, (b) R2* ratio (R2rat*) in obstructed kidneys and perirenal stranding, (c) medullary R2* in obstructed kidneys and duration since symptom onset, and (d) R2* ratio in obstructed kidneys and duration since symptom onset. Gray points = average R2* and R2* ratios in control subjects. For linear regression analyses (Pvalues and solid lines), only obstructed kidneys were considered (including that in the apparently outlying patient indicated by the dashed circles in c and d). With increasing stranding, R2* and R2* ratio declined in obstructed kidneys. Similarly, R2* and R2* ratio showed a trend to decline with increasing duration since symptom onset.
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Figure 3b: Graphs show relationships of (a) medullary R2* in obstructed kidneys and perirenal stranding, (b) R2* ratio (R2rat*) in obstructed kidneys and perirenal stranding, (c) medullary R2* in obstructed kidneys and duration since symptom onset, and (d) R2* ratio in obstructed kidneys and duration since symptom onset. Gray points = average R2* and R2* ratios in control subjects. For linear regression analyses (Pvalues and solid lines), only obstructed kidneys were considered (including that in the apparently outlying patient indicated by the dashed circles in c and d). With increasing stranding, R2* and R2* ratio declined in obstructed kidneys. Similarly, R2* and R2* ratio showed a trend to decline with increasing duration since symptom onset.
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Figure 3c: Graphs show relationships of (a) medullary R2* in obstructed kidneys and perirenal stranding, (b) R2* ratio (R2rat*) in obstructed kidneys and perirenal stranding, (c) medullary R2* in obstructed kidneys and duration since symptom onset, and (d) R2* ratio in obstructed kidneys and duration since symptom onset. Gray points = average R2* and R2* ratios in control subjects. For linear regression analyses (Pvalues and solid lines), only obstructed kidneys were considered (including that in the apparently outlying patient indicated by the dashed circles in c and d). With increasing stranding, R2* and R2* ratio declined in obstructed kidneys. Similarly, R2* and R2* ratio showed a trend to decline with increasing duration since symptom onset.
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Figure 3d: Graphs show relationships of (a) medullary R2* in obstructed kidneys and perirenal stranding, (b) R2* ratio (R2rat*) in obstructed kidneys and perirenal stranding, (c) medullary R2* in obstructed kidneys and duration since symptom onset, and (d) R2* ratio in obstructed kidneys and duration since symptom onset. Gray points = average R2* and R2* ratios in control subjects. For linear regression analyses (Pvalues and solid lines), only obstructed kidneys were considered (including that in the apparently outlying patient indicated by the dashed circles in c and d). With increasing stranding, R2* and R2* ratio declined in obstructed kidneys. Similarly, R2* and R2* ratio showed a trend to decline with increasing duration since symptom onset.
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DISCUSSION
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Our study results show a decrease in R2*, suggesting an increase in oxygen content, in the medulla and, to a lesser extent, in the cortex in patients with an acute unilateral ureteral obstruction due to a distal calculus. A substantially higher medullary R2* value, corresponding to a lower oxygen content, was observed in the contralateral nonobstructed kidney than in both the obstructed kidney and the kidneys of healthy volunteers.
To date, the data published on renal implications of acute obstruction of the kidneys are mainly based on the results of experimental studies (in dogs, pigs, rats) in which invasive methods were applied (16–19). During urinary tract obstruction, an increase in intraluminal pressure in the ureter and renal tubules is one of the first effects that can be detected (2). This leads to a decrease in the glomerular filtration rate (GFR), with impairment of water and solute excretion. In studies in rats (17,18), an immediate reduction in ipsilateral GFR after onset of acute ureteral obstruction has been shown. Similarly, ipsilateral GFR decreased by 75% during unilateral ureteral obstruction in pigs, whereas the filtration fraction increased temporarily, with a dramatic decrease thereafter (16). Our observations are in line with these findings, displaying an increase in oxygen content in the medulla due to a decrease in oxygen consumption. An increase in renal blood flow has been reported to result from augmented production of vasodilatory prostaglandins by the obstructed kidney during the acute phase (2)—another observation that corroborates our findings.
The significantly higher R2* ratio in the contralateral nonobstructed kidney than in the kidneys of a group of healthy volunteers, along with considerably though nonsignificantly higher medullary R2* values, indicate reduced oxygen content in the medulla of the contralateral nonobstructed kidney. This may be interpreted as a compensatory increase in glomerular filtration, with a subsequent increase in tubular fluid delivery and reabsorptive workload that finally leads to an increase in oxygen consumption. In addition, when unilateral pressure is increased in one kidney, the early phase of ipsilateral renal vasodilation is associated with contralateral vasoconstriction (2). This early mechanism involved in the nonobstructed kidney during unilateral ureteral ligation has been related to vasoconstriction mediated by increased nerve activity. This assumption has been confirmed in animal models by the fact that transsection of the spinal cord abolished the hemodynamic changes that occurred in the contralateral kidney when unilateral obstruction was produced (2). With prolonged obstruction, renal blood flow (RBF) of the ipsilateral kidney diminishes because of progressive vasoconstriction, whereas the nonobstructed kidney demonstrates a relatively preserved RBF or is exposed to higher concentrations of vasodilators such as prostaglandin E2, so RBF and glomerular filtration rate are maintained on a higher level than in the obstructed kidney (2,20). As a result, oxygen consumption because of the enhanced workload is expected to increase; this explains the low medullary oxygen content of the nonobstructed kidney.
To our knowledge, the effect of acute unilateral ureteral obstruction on the oxygen content of the obstructed and the contralateral nonobstructed kidney in humans as measured with BOLD MR imaging has not been previously reported. However, BOLD MR imaging results after ureteral obstruction have been reported from an experimental study performed in three pigs (13). In that investigation, a reduction in R2* could be observed in the medulla after induction of complete ureteral obstruction. However, in contrast to our findings, R2* was higher in the cortex of the obstructed kidneys, whereas in our study in humans, R2* was lower in the cortex of the obstructed kidney than in the cortex of the contralateral nonobstructed kidney. Furthermore, a reduced medullary R2* was also reported for the contralateral nonobstructed kidney, in contrast to our finding of compensatory increased medullary R2*. These differences might be attributed to the fact that our patients had only partial obstruction, whereas in the experimental animal study, the ureter was ligated for 24 hours, leading to a complete obstruction. The partial obstruction can explain the high oxygen content in the human renal cortex because partial obstruction preserves the cortical O2 delivery because of a less pronounced vasoconstriction (16). With progressive obstruction, vasoconstriction heightens, and, as a consequence, cortical O2 delivery is compromised. Likewise, in the animal models of total ureteral obstruction, pronounced vasoconstriction was observed to be accompanied by low oxygen content (13).
The different findings between our study and that of Pedersen et al (13) may also be related to medication effects. However, the reported findings on treatment effects on blood flow and oxygenation in cases of unilateral ureteral obstruction show a large variability. In an animal model (21), renal blood flow decreased in both kidneys with unilateral ureteral obstruction while recovering almost completely in the contralateral kidney within 15 hours. After treatment with indomethacin, vascular resistance increased dramatically on the affected side, with only a moderate increase contralaterally (21). Similarly, almost all patients in our study received NSAIDs, which inhibit prostaglandin synthesis. This leads to decreases in prostaglandin-mediated pain pathways, as well as decreases in ureteral contractility, renal pelvic and glomerular capillary pressure, and renal blood flow (22–24). No acute effects of NSAIDs on renal oxygenation were detected in a recent BOLD MR imaging study performed in healthy volunteers (25), although a tendency toward lower R2* values with time was reported.
The tendency toward increased oxygenation (lower R2*) with duration since onset of symptoms may be coincidental but may also indicate a continuous and cumulative increase in oxygen content in the medulla and a decrease in oxygen consumption, thus supporting the aforementioned interpretation. Furthermore, oxygen content increased in the medulla along with the extent of perirenal stranding. This could be attributed to a progression of renal vasoconstriction and a reduction in glomerular filtration with diminished tubular oxygen consumption with the increasing duration of the obstruction. Likewise, increased lymphatic pressure, and perhaps renal edema formation, might advance perirenal stranding, which ultimately might help to determine the time since onset of the obstruction.
Knowledge of the exact extent of obstruction might aid in decision making as to the right time point of intervention. Furthermore, information on changes in renal oxygen content during obstruction may be helpful to determine when ureteral obstruction impairs renal function. Therefore, functional evaluation of therapeutic strategies would provide more comprehensive information on the success of treatment. An important impact could be expected with respect to treatment with NSAIDs. High oxygen content in the diseased kidney could indicate marginal functional reserves in the presence of an increased exposure to oxidative stress, both of which would argue for alternative strategies to relieve the patient's discomfort.
BOLD MR imaging is a noninvasive tool that allows assessment of deterioration of renal function of the single kidney noninvasively. Thus, in contrast to isotopic nephrographic scintigraphy, MR imaging provides information on kidney morphology and function simultaneously, without radiation exposure and in a short time period (maximum examination time was about 15 minutes in our study). Another advantage of BOLD MR imaging is that there is no need to inject diuretics to demonstrate obstruction, as at scintigraphy, where furosemide is administered. Therefore, there is no risk of fornix rupture in patients with acute obstruction.
There were limitations to our study. First, despite the fact that the readers were blinded to clinical results, a potential bias when analyzing the results was unavoidable, because the side of the obstruction was visible on the MR images used for ROI selection. Furthermore, the reduced corticomedullary differentiation in obstructed kidneys may have led to ROI selections in the medulla having contributions from cortical tissue, which may have artificially reduced medullary R2* and also lowered the R2* ratio. However, the additional use of corresponding coronal T1-weighted images with normal corticomedullary differentiation for ROI placement reduced this effect. Second, BOLD MR imaging is unable to distinguish differences in Po2 levels produced by changes in oxygen supply from those produced by changes in oxygen consumption (4), limiting the physiologic interpretation of the results. Third, most of the patients took NSAIDs, which might influence the oxygenation status of the kidney. However, this as a sole explanation for our findings is unlikely because of the different findings in the obstructed and nonobstructed kidneys, which were both exposed to the medication. Fourth, follow-up of patients after successful treatment should be performed to ultimately determine the value of BOLD MR imaging for monitoring treatment response after acute unilateral ureteral obstruction is relieved.
In conclusion, BOLD MR imaging allows the noninvasive detection of functional alterations of the kidneys in patients with acute ureteral obstruction and therefore appears to hold promise as a tool in the assessment of the presence or absence of acute ureteral obstruction in a short time period and without ionizing radiation.
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ADVANCE IN KNOWLEDGE
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- Increased oxygen content in the renal cortex and medulla occurs with acute unilateral ureteral obstruction, suggesting reduced renal function of the affected kidney.
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IMPLICATIONS FOR PATIENT CARE
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- Blood oxygen level–dependent (BOLD) MR imaging allows noninvasive analysis of functional alterations of the obstructed and nonobstructed kidneys separately and without ionizing radiation.
- BOLD MR imaging has potential as a method for monitoring therapy of patients with acute ureteral obstruction.
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FOOTNOTES
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Abbreviations: BOLD = blood oxygen level dependent • NSAID = nonsteroidal antiinflammatory drug • ROI = region of interest
Author contributions: Guarantors of integrity of entire study, H.C.T., U.E.S.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, H.C.T., M.M., P.V.; clinical studies, H.C.T., T.M.K., S.S., P.V.; statistical analysis, T.M.K., F.D.K., P.V.; and manuscript editing, all authors
Authors stated no financial relationship to disclose.
See also Science to Practice in this issue.
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Z. J. Wang and B. M. Yeh
Is Assessing Renal Oxygenation by Using Blood Oxygen Level-Dependent MR Imaging a Clinical Reality?
Radiology,
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[Full Text]
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ABSTRACT
INTRODUCTION
