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Correlation analysis of urinary D/L-amino acid ratios and renal injury by using 5/6 nephrectomy model rats
Kosuke Fukuda1, Yutaka Umakoshi2, Kenichi Watanabe3
1Department of Biotechnology, Graduate School of Engineering, The University of Osaka, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan; Preclinical Research Unit, Sumitomo Pharma Co Ltd, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 554-0022, Japan.
Abstract:
Renal injury, such as chronic kidney disease (CKD), is a global public health problem. Recent studies have reported that several D/L-amino acid ratios are affected during renal injury; however, most reports have focused on renal dysfunction, and few have focused on the association between D/L-amino acid changes and histopathological alterations in the kidney. Therefore, we aimed to investigate the correlation between D/L-amino acid ratios and the histopathological findings of renal injury in a 5/6 nephrectomy rat model. In this study, the D/L-amino acid ratios were evaluated using urine samples collected 1, 2, 3, and 4 weeks after surgery. The D/L-Ser and D/L-Ala ratios were 3.0-fold and 9.3-fold higher, respectively, and the other D/L-amino acid ratios, such as D/L-Arg, D/L-Asn, D/L-His, D/L-Ile, D/L-Lys, D/L-Phe, and D/L-Thr ratios, also showed higher values than those in the sham group. The D/L-amino acid ratios in the urine were consistently maintained throughout the evaluation period compared to those in the sham group. However, only the D/L-Gln ratio was lower than that in the sham group. Correlation analysis between D/L-amino acid ratios and histopathological alterations in the kidney revealed a good correlation between D/L-Ala, D/L-Glu, and D/L-Gln one week after surgery and tubular dilatation. No other findings showed a strong correlation with the changes in the D/L-amino acid ratios of the aforementioned amino acids. By evaluating urinary D/L-amino acid ratios, we could potentially detect tubular dilatation in the kidney noninvasively and obtain insights into the physiological condition of the kidney.
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