Assessment with Unenhanced MRI Techniques of Renal Morphology and Hemodynamic Changes during Acute Kidney Injury and Chronic Kidney Disease in Mice

Abstract

Background/Aims: Changes in renal oxygenation and perfusion have been identified as common pathways to the development and progression of renal disease. Recently, the sensitivity of hemodynamic response imaging (HRI) was demonstrated; this is a functional magnetic resonance imaging (MRI) method combined with transient hypercapnia and hyperoxia for the evaluation of renal perfusion and vascular reactivity. The aim of this study was to utilize HRI for the noninvasive evaluation of changes in renal hemodynamics and morphology during acute, chronic and acute-on-chronic renal failures. Methods: Renal-HRI maps and true fast imaging with steady-state precession (True-FISP) images were used to evaluate renal perfusion, morphology and corticomedullary differentiation (CMD). MR images were acquired on two mouse models of kidney injury: adenine-induced chronic kidney disease (CKD) and rhabdomyolysis-induced acute kidney injury (AKI). Serum urea was measured from these mice in order to determine renal function. Results: Renal-HRI maps revealed a blunted response to hypercapnia and hyperoxia with evolving kidney dysfunction in both models, reflecting hampered renal vascular reactivity and perfusion. True-FISP images showed a high sensitivity to renal morphological changes, with different patterns characterizing each model. Calculated data obtained from HRI and True-FISP during the evolution of renal failure and upon recovery, with and without protective intervention, closely correlated with the degree of renal impairment. Conclusions: This study suggests the potential combined usage of two noninvasive MRI methods, HRI and True-FISP, for the assessment of renal dysfunction without the potential risk associated with contrast-agents administration. HRI may also serve as a research tool in experimental settings, revealing the hemodynamic changes associated with kidney dysfunction.

Renal cellular hypoxia in adenine‐induced chronic kidney disease

“…We are not aware of any published reports of renal vascular structure in adenine‐induced CKD. However, Milman and colleagues recently provided evidence of blunted perfusion and renal vascular reactivity in anaesthetised mice with adenine‐induced CKD, using a magnetic resonance imaging technique for assessing the renal vascular response to hyperoxia . Consistent with these observations, renal blood flow measured directly by transit‐time ultrasound flowmetry or electromagnetic flowmetry under anaesthesia, and by the clearance of para‐aminohippurate in the conscious state, has been observed to be less in rats with adenine‐induced CKD compared to control animals.…”

“…Consequently, we require experimental models of CKD in which pathological changes in renal tissue develop rapidly in response to a defined stimulus. Administration of adenine, either in food or by oral gavage, has been shown to result in reproducible renal dysfunction. Adenine is metabolised to 2,8‐dihydroxy‐adenine which forms crystalline casts within the renal tubules.…”

Microvascular resistance in response to iodinated contrast media in normal and functionally impaired kidneys

“…Similarly, in an experimental model, renal blood flow in rats with normal renal function temporarily decreased after exposure to contrast media, whereas in those with impaired renal function, the renal blood flow did not decrease . Indeed, several experimental studies have shown attenuated functional derangement against acute structural damages, including hypoxic stress, in CKD, and a recent experimental study using magnetic resonance imaging demonstrated less haemodynamic change following hypoxic stress in mice models of CKD than in normal mice . Further research is therefore needed to evaluate the differing renal artery responses to iodinated contrast media in patients with both normal and impaired kidney function.…”

Innovative Perspective: Gadolinium-Free Magnetic Resonance Imaging in Long-Term Follow-Up after Kidney Transplantation

“…Although a lower corticomedullary sodium gradient has been demonstrated in kidney allografts in comparison to native kidneys, sodium imaging has neither been able to reflect kidney function in kidney transplantation patients (Moon et al, 2014), nor in healthy individuals with a variety of eGFRs (Haneder et al, 2013), and is therefore not discussed in detail. However, it must be pointed out that preliminary experimental results in other kidney disease states, such as acute tubular necrosis, have shown changes in sodium imaging (Maril et al, 2006; Atthe et al, 2009), Similar to sodium MRI, hemodynamic response imaging has only been applied in experimental settings in animals thus far (Milman et al, 2013, 2014) .…”

“…In this way hemodynamic changes due to Bohr-effect and CO 2 -induced vasodilation are provoked, for instance in the kidney, which enables evaluation of regional vascular reactivity. To date, only two studies in experimental animals have investigated kidney HRI (Milman et al, 2013, 2014). …”