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Abstract: TH-PO952

Near-Infrared Autofluorescence Is Useful for Non-Invasive Imaging of Injured Kidneys

Session Information

Category: Pathology and Lab Medicine

  • 1501 Pathology and Lab Medicine: Basic

Authors

  • Matsumoto, Ayumi, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Matsui, Isao, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Shimada, Karin, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Hashimoto, Nobuhiro, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Doi, Yohei, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Yamaguchi, Satoshi, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Kubota, Keiichi, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Oka, Tatsufumi, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Sakaguchi, Yusuke, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Hamano, Takayuki, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Takabatake, Yoshitsugu, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
  • Isaka, Yoshitaka, Osaka University Graduate School of Medicine, Suita, OSAKA-FU, Japan
Background

Tubulointerstitial injury (TI) is the final common pathway leading to end-stage renal disease. Because TI is an important therapeutic target in kidney diseases, it is indispensable to establish non-invasive strategies that enable us to evaluate the progression of TI.

Methods

Near-infrared autofluorescence (AF) of injured kidney was non-invasively evaluated by IVIS imaging system. A combination of excitation 710 nm and emission 810-875 nm was used. Two animal models, unilateral ureteral obstruction and folic acid induced nephropathy, in BALB/c mice were analyzed. The origin of the renal AF was analyzed by confocal microscopy. Normal portions of human kidney tissues obtained from surgically resected kidneys owing to malignant tumors were also analyzed (35 patients (male 20, female 15), median age 69 (interquartile range (IQR) 62-74), median estimated glomerular filtration rate (eGFR) 57.25 mL/min/1.73m2 (IQR 38.9-73.45)).

Results

The AF levels were positively correlated with the progression of TI in both animal models. Microscopic analysis of the kidney sections revealed that the AF was originated from the injured tubular cells. Because porphyrins are intrinsic fluorescent substrates that have near-infrared emission peak, we analyzed renal expression levels of enzymes that participate in the metabolism of porphyrin. Among 10 enzymes, only coproporphyrinogen oxidase (CPOX) was suppressed in the injured kidneys in both animal models, suggesting that coproporphrinogen III, a substrate for CPOX, and its spontaneously oxidized product, coproporphyrin III, were accumulated in the injured kidneys. We found that coproporphyrin III had identical fluorescent properties observed in the injured kidneys. Intraperitoneal injection of δ-aminolevulinic acid, a substrate of porphyrin synthesis, enhanced the AF of injured kidneys. The AF was also enhanced in BALB/c-nct/nct mice, a mice strain that retains only 15% of the wild type CPOX activity. Furthermore, AF levels of human kidney samples were inversely associated with eGFR.

Conclusion

Near-infrared AF derived from coproporphyrin III is useful for non-invasive imaging of TI.