BOLD-MRI for the assessment of renal oxygenation in humans: acute effect of nephrotoxic xenobiotics

Hypoxia of renal medulla is a key factor implicated in the development of drug-induced renal failure. Drugs are known to influence renal hemodynamics and, subsequently, affect renal tissue oxygenation. Changes in renal oxygenation can be assessed non-invasively in humans using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI). This study was designed to test the acute effects of administration of specific drugs in healthy human kidney oxygenation using BOLD-MRI. Acute changes in renal tissue oxygenation induced by the non-steroidal anti-inflammatory drug indomethacin, the iodinated radio-contrast media (RCM) iopromidum, and the calcineurin inhibitors cyclosporine micro-emulsion (CsA-ME) and tracrolimus were studied in 30 healthy volunteers. A modified Multi Echo Data Image Combination sequence was used to acquire 12 T(2)(*)-weighted images. Four coronal slices were selected to cover both kidneys. The mean R(2)(*) (1/T(2)(*)) values determined in medulla and cortex showed no significant changes induced by indomethacin and tacrolimus administration. CsA-ME decreased medullary (P=0.008) and cortical (P=0.004) R(2)(*) values 2 h after ingestion. Iopromidum caused a significant increase in medullary R(2)(*) within the first 20 min after injection (P<0.001), whereas no relevant changes were observed in renal cortex. None of the measurements showed left-right kidney differences. Significant differences in renal medullary oxygenation were evidenced between female and male subjects (P=0.013). BOLD-MRI was efficient to show effects of specific drugs in healthy renal tissue. Cyclosporine increased renal medullary oxygenation 2 h after ingestion of a single dose, whereas indomethacin and tacrolimus showed no effect on renal oxygenation. Injection of iodinated RCM decreased renal medullary oxygenation.

Non-invasive monitoring of renal oxygenation using BOLD-MRI: a reproducibility study

Blood oxygenation level-dependent (BOLD) MRI was shown to allow non-invasive observation of renal oxygenation in humans. However, clinical applications of this type of functional MRI of the kidney are still limited, most likely because of difficulties in obtaining reproducible and reliable information. The aim of this study was to evaluate the reproducibility and robustness of a BOLD method applied to the kidneys and to identify systematic physiological changes potentially influencing the renal oxygenation of healthy volunteers. To measure the BOLD effect, a modified multi-echo data image combination (MEDIC) sequence was used to acquire 12 T2*-weighted images within a single breath-hold. Three identical measurements were performed on three axial and three coronal slices of right and left kidneys in 18 volunteers. The mean R2* (1/T2*) values determined in medulla and cortex showed no significant differences over three repetitions and low intra-subject coefficients of variation (CV) (3 and 4% in medulla and cortex, respectively). The average R2* values were higher in the medulla (16.15 +/- 0.11) than in the cortex (11.69 +/- 0.18) (P < 0.001). Only a minor influence of slice orientation was observed. Mean R2* values were slightly higher (3%) in the left than in the right kidney (P < 0.001). Differences between volunteers were identified (P < 0.001). Part of these differences was attributable to age-dependent R2* values, since these values increased with age when medulla (P < 0.001, r = 0.67) or cortex (P < 0.020, r = 0.42) were considered. Thus, BOLD measurements in the kidney are highly reproducible and robust. The results allow one to identify the known cortico-medullary gradient of oxygenation evidenced by the gradient of R2* values and suggest that medulla is more hypoxic in older than younger individuals. BOLD-MRI is therefore a useful tool to study sequentially and non-invasively regional oxygenation of human kidneys.

Renal oxygenation changes during acute unilateral ureteral obstruction: assessment with blood oxygen level-dependent mr imaging--initial experience

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 Po(2). 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.

Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers

BACKGROUND Cocoa is rich in flavonoids, has anti-oxidative properties and increases the bioavailability of nitric oxide (NO). Adequate renal tissue oxygenation is crucial for the maintenance of renal function. The goal of this study was to investigate the effect of cocoa-rich dark chocolate (DC) on renal tissue oxygenation in humans, as compared to flavonoid-poor white chocolate (WC). METHODS Ten healthy volunteers with preserved kidney function (mean age ± SD 35 ± 12 years, 70% women, BMI 21 ± 3 kg/m2) underwent blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) before and 2 hours after the ingestion of 1 g/kg of DC (70% cocoa). Renal tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* (= 1/T2*) values in the medulla and cortex were calculated, a low R2* indicating high tissue oxygenation. Eight participants also underwent BOLD-MRI at least 1 week later, before and 2 hours after the intake of 1 g/kg WC. RESULTS The mean medullary R2* was lower after DC intake compared to baseline (28.2 ± 1.3 s-1 vs. 29.6 ± 1.3 s-1, p = 0.04), whereas cortical and medullary R2* values did not change after WC intake. The change in medullary R2* correlated with the level of circulating (epi)catechines, metabolites of flavonoids (r = 0.74, p = 0.037), and was independent of plasma renin activity. CONCLUSION This study suggests for the first time an increase of renal medullary oxygenation after intake of dark chocolate. Whether this is linked to flavonoid-induced changes in renal perfusion or oxygen consumption, and whether cocoa has potentially renoprotective properties, merits further study.

Living Renal Allograft Transplantation: Diffusion-weighted MR Imaging in Longitudinal Follow-up of the Donated and the Remaining Kidney.

Purpose To determine whether diffusion-weighted (DW) magnetic resonance (MR) imaging in living renal allograft donation allows monitoring of potential changes in the nontransplanted remaining kidney of the donor because of unilateral nephrectomy and changes in the transplanted kidney before and after transplantation in donor and recipient, respectively, and whether DW MR parameters are correlated in the same kidney before and after transplantation. Materials and Methods The study protocol was approved by the local ethics committee; written informed consent was obtained. Thirteen healthy kidney donors and their corresponding recipients prospectively underwent DW MR imaging (multiple b values) in donors before donation and in donors and recipients at day 8 and months 3 and 12 after donation. Total apparent diffusion coefficient (ADCT) values were determined; contribution of microcirculation was quantified in perfusion fraction (FP). Longitudinal changes of diffusion parameters were compared (repeated-measures one-way analysis of variance with post hoc pairwise comparisons). Correlations were tested (linear regression). Results ADCT values in nontransplanted kidney of donors increased from a preexplantation value of (188 ± 9 [standard deviation]) to (202 ± 11) × 10(-5) mm(2)/sec in medulla and from (199 ± 11) to (210 ± 13) × 10(-5) mm(2)/sec in cortex 1 week after donation (P < .004). Medullary, but not cortical, ADCT values stayed increased up to 1 year. ADCT values in allografts in recipients were stable. Compared with values obtained before transplantation in donors, the corticomedullary difference was reduced in allografts (P < .03). Cortical ADCT values correlated with estimated glomerular filtration rate in recipients (R = 0.56, P < .001) but not donors. Cortical ADCT values in the same kidney before transplantation in donors correlated with those in recipients on day 8 after transplantation (R = 0.77, P = .006). FP did not show significant changes. Conclusion DW MR imaging depicts early adaptations in the remaining nontransplanted kidney of donors after nephrectomy. All diffusion parameters remained constant in allograft recipients after transplantation. This method has potential monitoring utility, although assessment of clinical relevance is needed. © RSNA, 2013 Online supplemental material is available for this article.

Effect of sodium loading/depletion on renal oxygenation in young normotensive and hypertensive men

The goal of this study was to investigate the effect of sodium intake on renal tissue oxygenation in humans. To this purpose, we measured renal hemodynamics, renal sodium handling, and renal oxygenation in normotensive (NT) and hypertensive (HT) subjects after 1 week of a high-sodium and 1 week of a low-sodium diet. Renal oxygenation was measured using blood oxygen level-dependent magnetic resonance. Tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* values in the medulla and cortex were calculated, with a low R2* indicating a high tissue oxygenation. Ten male NT (mean age: 26.5+/-7.4 years) and 8 matched HT subjects (mean age: 28.8+/-5.7 years) were studied. Cortical R2* was not different under the 2 conditions of salt intake. Medullary R2* was significantly lower under low sodium than high sodium in both NT and HT subjects (28.1+/-0.8 versus 31.3+/-0.6 s(-1); P<0.05 in NT; and 27.9+/-1.5 versus 30.3+/-0.8 s(-1); P<0.05, in HT), indicating higher medullary oxygenation under low-sodium conditions. In NT subjects, medullary oxygenation was positively correlated with proximal reabsorption of sodium and negatively with absolute distal sodium reabsorption, but not with renal plasma flow. In HT subjects, medullary oxygenation correlated with the 24-hour sodium excretion but not with proximal or with the distal handling of sodium. These data demonstrate that dietary sodium intake influences renal tissue oxygenation, low sodium intake leading to an increased renal medullary oxygenation both in normotensive and young hypertensive subjects.

Arterial Hypertension Refractory to Renal Denervation, Abdominal Pain and Claudication: Any Coral’ations?

Coral reef aorta is a rare form of calcifying atherosclerosis typically involving the supra and juxtarenal aorta. P atients classically present with refractory hypertension, intermittent claudication and abdominal angina. The treatment is either surgical via transaortic endarterectomy or through transferal endovascular stentgraft placement. Here we describe the case of a 45yearold female patient infected with human immuno deficiency virus, with resistant hypertension, lower limb and abdominal claudication, who was successfully treated with endovascular stent placement. We f urther provide a brief overview of the disease characteristics and treatment options.

Renal Blood Oxygenation Level-dependent Imaging in Longitudinal Follow-up of Donated and Remaining Kidneys

Purpose To determine renal oxygenation changes associated with uninephrectomy and transplantation in both native donor kidneys and transplanted kidneys by using blood oxygenation level-dependent (BOLD) MR imaging. Materials and Methods The study protocol was approved by the local ethics committee. Thirteen healthy kidney donors and their corresponding recipients underwent kidney BOLD MR imaging with a 3-T imager. Written informed consent was obtained from each subject. BOLD MR imaging was performed in donors before uninephrectomy and in donors and recipients 8 days, 3 months, and 12 months after transplantation. R2* values, which are inversely related to tissue partial pressure of oxygen, were determined in the cortex and medulla. Longitudinal R2* changes were statistically analyzed by using repeated measures one-way analysis of variance with post hoc pair-wise comparisons. Results R2* values in the remaining kidneys significantly decreased early after uninephrectomy in both the medulla and cortex (P < .003), from 28.9 sec(-1) ± 2.3 to 26.4 sec(-1) ± 2.5 in the medulla and from 18.3 sec(-1) ± 1.5 to 16.3 sec(-1) ± 1.0 in the cortex, indicating increased oxygen content. In donors, R2* remained significantly decreased in both the medulla and cortex at 3 (P < .01) and 12 (P < .01) months. In transplanted kidneys, R2* remained stable during the first year after transplantation, with no significant change. Among donors, cortical R2* was found to be negatively correlated with estimated glomerular filtration rate (R = -0.47, P < .001). Conclusion The results suggest that BOLD MR imaging may potentially be used to monitor renal functional changes in both remaining and corresponding transplanted kidneys. (©) RSNA, 2016.