Abstract
Membranous nephropathy (MN) is the major cause of adult nephrotic syndrome, which severely affects patients’ quality of life. Currently, percutaneous renal biopsy is required to definitively diagnose MN. However, this technique is invasive and may cause severe complications. Therefore, an urgent clinical need exists for dynamic noninvasive monitoring of the renal state. In-depth molecular imaging studies could assist in finding a solution. Membrane attack complex C5b-9 is the key factor in the development of MN, and this protein primarily deposits in the glomerulus. The present study bound polyclonal antibodies to C5b-9 with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to obtain C5b-9-targeted magnetic resonance molecular imaging probes. The probes were injected intravenously into rats with Heymann nephritis, a classic disease model of MN. The signal intensity in the T2*-weighted imaging of kidneys in vivo using 7.0 Tesla magnetic resonance imaging decreased significantly 24 hours after injection compared to the untargeted and control groups. This signal change was consistent with the finding of nanoparticle deposits in pathological glomeruli. This study demonstrated a novel molecular imaging technique for the assessment of MN.
Highlights
Membranous nephropathy (MN) is the major cause of adult nephrotic syndrome, and the pathogenesis of MN has not been yet fully elucidated
Molecular imaging studies in the kidneys have mainly focused on tracking transplanted stem cells in patients with kidney failure, and few studies have reported on nephropathy, including nephrotic syndrome and glomerulonephritis
Several studies have reported the use of ultrasmall superparamagnetic iron oxide (USPIO) for the evaluation of nephropathy
Summary
Membranous nephropathy (MN) is the major cause of adult nephrotic syndrome, and the pathogenesis of MN has not been yet fully elucidated. The immune complex sediments induce complements to produce C5b-9, which activates a signaling pathway that causes GEC injuries and GBM damage, leading to albuminuria. The development of molecular magnetic resonance imaging (MRI) provides new opportunities to monitor pathological changes in kidneys in vivo. MRI contrast agents, such as ultrasmall superparamagnetic iron oxide (USPIO), can be combined with specific antibodies to form complex-targeting molecular probes. The magnetization properties of USPIO in the probes may change the T1/T2 relaxation time of tissues, and specific MRI findings of the targeting complex can be obtained [9]. We injected the probe intravenously into rats with passive HN with the objective of studying whether the C5b-9-targeting probe could feasibly evaluate the pathological progress in the kidneys of rats using in vivo MRI at an ultrahigh field strength in a 7.0 Tesla MRI scanner
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