MR imaging of intrarenal macrophage infiltration in an experimental model of nephrotic syndrome

Abstract

The objective of this study was to use MR imaging to detect macrophage infiltration of the kidney after injection of ultrasmall superparamagnetic iron oxide (USPIO) particles in a rat model of experimental nephropathy. Ninety mol of USPIO were injected intravenously in 10 rats with nephropathy secondary to intravenous injection of 5 mg of puromycin aminonucleoside (PAN), and in 10 control rats. The signal intensity was measured in each kidney compartment before and 24 h after injection of the contrast agent. FLASH sequences were performed on a spectrometer operating at 4.7 T. MR findings were compared with histological data. Twenty-four hours after injection of USPIO, a significant decrease (P F 0.0001) was observed in signal intensity in each kidney compartment in the PAN group. There was no variation in the control group. In the diseased kidneys, histological data revealed the presence of macrophages with iron oxide particles within their cytoplasm and lysosomes. Using USPIO, MR imaging can evidence infiltration of the rat kidney by macrophages. Magn Reson Med 41:156-162, 1999. 1999 Wiley-Liss, Inc.

USPIO-enhanced MR imaging of macrophage infiltration in native and transplanted kidneys: initial results in humans

“…In the kidney, several previous animal experiments in rats demonstrated that in vivo targeting of intrarenal macrophages or activated mesangial cells by USPIO was possible [9][10][11][12][13]. Intensity of intrarenal signal change seemed to correlate well to the level of iron content, to the degree of macrophage infiltration, and to the degree of renal dysfunction.…”

“…Previous experimental studies on rats have shown that MR imaging, with intravenous infusion of USPIO, by showing a signal decrease in various kidney compartments, could serve as a non-invasive method to demonstrate intrarenal endocytic activity in various models of nephritides [9,11], including renal graft rejection [12] and acute renal failure following ischemia [10].…”

“…Fourteen patients received a dose of 1.7 mg of iron/kg (0.085 ml/kg), corresponding to the dose extrapolated from previous experimental studies on animal models [9,11], and seven patients received a higher dose of 2.6 mg of iron/ kg (0.13 ml/kg), as performed in other studies on lymph nodes [6,7], atheroma or multiple sclerosis [8], in order to evaluate its clinical and biological tolerance as well as its effectiveness for reducing signal intensity. It was administrated through a vial with a 5-μm filter as an intravenous infusion at a rate of 4 ml/min.…”

“…Intensity of intrarenal signal change seemed to correlate well to the level of iron content, to the degree of macrophage infiltration, and to the degree of renal dysfunction. Interestingly, the location of the maximal signal change depended on the type of nephropathy: exclusively cortical in experimental anti-glomerular basement membrane (anti-GBM) glomerulonephritis [9], exclusively medullar in ischemia-reperfusion [10] and diffuse in an experimental model of nephrotic syndrome [11], in urinary obstruction [9] and in experimental models of acute [12] and chronic [13] renal graft rejection. To our knowledge, no investigation using intravenous administration of USPIO for kidney diseases in humans has been conducted so far.…”

Cellular Magnetic Labeling with Iron Oxide Nanoparticles

“…In this context of brain damages associated with inflammatory events, macrophage activity has been studied by MRI after USPIO infusion also in human patients suffering from stroke [92]. In vivo cellular MR imaging of USPIO-labeled macrophages has found successful applications in other animal models of disease, such as in kidney injuries (nephropathies) induced by a nephrotoxic drug (puromycin aminonucleoside) or in organ graft rejection (e.g., after renal allograft transplantation without any immunosuppressive drug) [3,93,94]. The accumulation of long-circulating USPIO in monocytes and macrophages recruited to atherosclerotic plaques has been demonstrated also in hyperlipidemic rabbits [95,96].…”