Background/Purpose: Glomerulonephritis (GN) represents a major cause of morbidity & mortality. The standard for diagnosing GN is through renal biopsy, but this is not performed uniformly across many centers. There is an unmet need to identify a noninvasive approach for recognizing GN. Recent advances in deep tissue imaging using probes detected by nearinfrared (NIR) wavelengths have enabled the noninvasive probing of biologic activity. Macrophage infiltration of the kidney is observed in early GN and once activated, express the cysteine protease cathepsin B. Thus, renal macrophage activation can be assessed using an NIR probe that becomes fluorescent upon cleavage by cathepsin B. We tested the ability of using NIR optical imaging to assess renal macrophage activation as a noninvasive marker for early-stage GN.

Methods: GN was induced in 129 mice by nephrotoxic serum (NTS) delivered intravenously (IV). Proteinuria was assessed using albumin ELISA & chromogenic creatinine assay. H&E and PAS stained slides of mouse kidneys were observed using light microscopy. Presence of renal macrophages was confirmed using FACS. NIR optical imaging of anesthetized mice was performed following IV administration of a cleavable sensor for cathepsin B & fluorescence intensity of kidney regions quantified.

Results: In mice with uninflamed kidneys, we confirmed the paucity of renal macrophages. Accordingly, there was minimal renal fluorescence signal as determined by fluorescent molecular imaging of cathepsin B activity. 3 days post-NTS administration, we observed a massive influx of macrophages into the kidney, along with nephrotic range proteinuria. This correlated with a significant increase in renal fluorescence intensity signal in NTS mice compared to control mice.

Conclusion: Induction of GN by NTS caused significant macrophage infiltration, which was detected noninvasively by a cathepsin B-activatable probe and NIR optical imaging. These data establish the proof-of-principle that NIR optical imaging may represent a translatable approach to establishing early stages of GN.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/noninvasive-assessment-of-macrophage-activation-in-experimental-glomerulonephritis-using-optical-imaging-with-near-infrared-light-serves-as-a-surrogate-of-disease-activity/