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

Abstract

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 investigation of kidney disease in type 1 diabetes by magnetic resonance imaging

“…Such approaches offer significant advantages in detecting pathological changes that may be regional or heterogeneous in their effects, and are forming the basis of our future studies. Renal T 2 * and BOLD contrast Although we could confirm the previously reported differences between the R 2 * of the cortex and medulla [17,19], we observed no change in renal R 2 * on physiological perturbation [21,34,35] as previously ascribed to changes in tissue oxygenation via BOLD contrast mechanisms [36]. Some earlier studies have employed hand-placed regions of interest to assess changes in R 2 * , typically using T 2 * or R 2 * maps to guide selection of ROI position.…”

“…These methods have been translated from brain imaging studies that employ changes in tissue R 2 * to report on neural activity via blood oxygenation [13]. Applied to renal tissue, studies have suggested that changes in cortical and medullary oxygenation can be monitored via R 2 * mapping, and that tissue oxygenation change in response to physiological perturbations (including water loading) can differ between normal and disease states [14][15][16][17][18][19], including type 2 diabetes [20,21].…”

Renal Parenchymal Hypoxia, Hypoxia Adaptation, and the Pathogenesis of Radiocontrast Nephropathy

“…Radiocontrast administration induces a host of systemic effects that may compromise renal tissue oxygenation, including pulmonary ventilation-perfusion mismatch, reduced cardiac output and renal perfusion pressure, altered rheologic properties of the blood, and increased oxygen-hemoglobin association (12). However, the greater part of the decline in renal parenchymal oxygenation can be attributed to altered intrarenal balance of oxygen supply and demand, summarized in Figure 2 and as discussed in the sections that follow.…”

Blood oxygenation level-dependent MRI for assessment of renal oxygenation

“…12,22,42,[55][56][57][58][59] In rats treated with cyclooxygenase and nitric oxide synthase inhibitors, administration of a first-generation ionic hyperosmolar contrast agent reduced medullary oxygenation. 55 Administration of a third-generation nonionic, iso-osmolar, high viscosity contrast agent caused an even greater reduction in medullary oxygenation.…”