The Possibility of Urinary Liver-Type Fatty Acid-Binding Protein as a Biomarker of Renal Hypoxia in Spontaneously Diabetic Torii Fatty Rats
Background: Renal hypoxia is an aggravating factor for tubulointerstitial damage, which is strongly associated with renal prognosis in diabetic kidney disease (DKD). Therefore, urinary markers that can detect renal hypoxia are useful for monitoring DKD. Objective: To determine the correlation betwee...
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doaj-2117cabdef67421296f8531c3092ecaf2020-11-25T03:42:10ZengKarger PublishersKidney & Blood Pressure Research1420-40961423-01432019-11-014461476149210.1159/000503926503926The Possibility of Urinary Liver-Type Fatty Acid-Binding Protein as a Biomarker of Renal Hypoxia in Spontaneously Diabetic Torii Fatty RatsJun TanabeYuji OguraMikie NakabayashiYoshio NagaiShiika WatanabeTakeshi SugayaKeiichi OhataDaisuke IchikawaKazuho InoueSeiko HoshinoKenjiro KimuraYugo ShibagakiYumie OnoAtsuko Kamijo-IkemoriBackground: Renal hypoxia is an aggravating factor for tubulointerstitial damage, which is strongly associated with renal prognosis in diabetic kidney disease (DKD). Therefore, urinary markers that can detect renal hypoxia are useful for monitoring DKD. Objective: To determine the correlation between urinary liver-type fatty acid-binding protein (L-FABP) and renal hypoxia using a novel animal model of type 2 diabetes. Methods: Male spontaneously diabetic Torii (SDT) fatty rats (n = 6) were used as an animal model of type 2 diabetes. Age- and sex-matched Sprague-Dawley (SD) rats (n = 8) were used as controls. Body weight, systolic blood pressure, and blood glucose levels were measured at 8, 12, 16, and 24 weeks of age. Urine samples and serum and kidney tissues were collected at 24 weeks of age. Microvascular blood flow index (BFI) was measured using diffuse correlation spectroscopy before sampling both the serum and kidneys for the evaluation of renal microcirculation at the corticomedullary junction. Results: Obesity, hyperglycemia, and hypertension were observed in the SDT fatty rats. Focal glomerular sclerosis, moderate interstitial inflammation, and fibrosis were significantly more frequent in SDT fatty rats than in SD rats. While the frequency of peritubular endothelial cells and phosphoendothelial nitric oxide synthase levels were similar in both types of rats, the degree of renal hypoxia-inducible factor-1α (HIF-1α) expression was significantly higher (and with no change in renal vascular endothelial growth factor expression levels) in the SDT fatty rats. Urinary L-FABP levels were significantly higher and renal microvascular BFI was significantly lower in the SDT fatty rats than in the SD rats. Urinary L-FABP levels exhibited a significant positive correlation with renal HIF-1α expression and a significant negative correlation with renal microvascular BFI. Conclusions: Urinary L-FABP levels reflect the degree of renal hypoxia in DKD in a type 2 diabetic animal model. Urinary L-FABP may thus prove useful as a renal hypoxia marker for monitoring DKD in patients with type 2 diabetes in clinical practice.https://www.karger.com/Article/FullText/503926diabetesdiabetic kidney diseasehypoxiakidneyliver-type fatty acid-binding proteintubulointerstitial damage |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jun Tanabe Yuji Ogura Mikie Nakabayashi Yoshio Nagai Shiika Watanabe Takeshi Sugaya Keiichi Ohata Daisuke Ichikawa Kazuho Inoue Seiko Hoshino Kenjiro Kimura Yugo Shibagaki Yumie Ono Atsuko Kamijo-Ikemori |
spellingShingle |
Jun Tanabe Yuji Ogura Mikie Nakabayashi Yoshio Nagai Shiika Watanabe Takeshi Sugaya Keiichi Ohata Daisuke Ichikawa Kazuho Inoue Seiko Hoshino Kenjiro Kimura Yugo Shibagaki Yumie Ono Atsuko Kamijo-Ikemori The Possibility of Urinary Liver-Type Fatty Acid-Binding Protein as a Biomarker of Renal Hypoxia in Spontaneously Diabetic Torii Fatty Rats Kidney & Blood Pressure Research diabetes diabetic kidney disease hypoxia kidney liver-type fatty acid-binding protein tubulointerstitial damage |
author_facet |
Jun Tanabe Yuji Ogura Mikie Nakabayashi Yoshio Nagai Shiika Watanabe Takeshi Sugaya Keiichi Ohata Daisuke Ichikawa Kazuho Inoue Seiko Hoshino Kenjiro Kimura Yugo Shibagaki Yumie Ono Atsuko Kamijo-Ikemori |
author_sort |
Jun Tanabe |
title |
The Possibility of Urinary Liver-Type Fatty Acid-Binding Protein as a Biomarker of Renal Hypoxia in Spontaneously Diabetic Torii Fatty Rats |
title_short |
The Possibility of Urinary Liver-Type Fatty Acid-Binding Protein as a Biomarker of Renal Hypoxia in Spontaneously Diabetic Torii Fatty Rats |
title_full |
The Possibility of Urinary Liver-Type Fatty Acid-Binding Protein as a Biomarker of Renal Hypoxia in Spontaneously Diabetic Torii Fatty Rats |
title_fullStr |
The Possibility of Urinary Liver-Type Fatty Acid-Binding Protein as a Biomarker of Renal Hypoxia in Spontaneously Diabetic Torii Fatty Rats |
title_full_unstemmed |
The Possibility of Urinary Liver-Type Fatty Acid-Binding Protein as a Biomarker of Renal Hypoxia in Spontaneously Diabetic Torii Fatty Rats |
title_sort |
possibility of urinary liver-type fatty acid-binding protein as a biomarker of renal hypoxia in spontaneously diabetic torii fatty rats |
publisher |
Karger Publishers |
series |
Kidney & Blood Pressure Research |
issn |
1420-4096 1423-0143 |
publishDate |
2019-11-01 |
description |
Background: Renal hypoxia is an aggravating factor for tubulointerstitial damage, which is strongly associated with renal prognosis in diabetic kidney disease (DKD). Therefore, urinary markers that can detect renal hypoxia are useful for monitoring DKD. Objective: To determine the correlation between urinary liver-type fatty acid-binding protein (L-FABP) and renal hypoxia using a novel animal model of type 2 diabetes. Methods: Male spontaneously diabetic Torii (SDT) fatty rats (n = 6) were used as an animal model of type 2 diabetes. Age- and sex-matched Sprague-Dawley (SD) rats (n = 8) were used as controls. Body weight, systolic blood pressure, and blood glucose levels were measured at 8, 12, 16, and 24 weeks of age. Urine samples and serum and kidney tissues were collected at 24 weeks of age. Microvascular blood flow index (BFI) was measured using diffuse correlation spectroscopy before sampling both the serum and kidneys for the evaluation of renal microcirculation at the corticomedullary junction. Results: Obesity, hyperglycemia, and hypertension were observed in the SDT fatty rats. Focal glomerular sclerosis, moderate interstitial inflammation, and fibrosis were significantly more frequent in SDT fatty rats than in SD rats. While the frequency of peritubular endothelial cells and phosphoendothelial nitric oxide synthase levels were similar in both types of rats, the degree of renal hypoxia-inducible factor-1α (HIF-1α) expression was significantly higher (and with no change in renal vascular endothelial growth factor expression levels) in the SDT fatty rats. Urinary L-FABP levels were significantly higher and renal microvascular BFI was significantly lower in the SDT fatty rats than in the SD rats. Urinary L-FABP levels exhibited a significant positive correlation with renal HIF-1α expression and a significant negative correlation with renal microvascular BFI. Conclusions: Urinary L-FABP levels reflect the degree of renal hypoxia in DKD in a type 2 diabetic animal model. Urinary L-FABP may thus prove useful as a renal hypoxia marker for monitoring DKD in patients with type 2 diabetes in clinical practice. |
topic |
diabetes diabetic kidney disease hypoxia kidney liver-type fatty acid-binding protein tubulointerstitial damage |
url |
https://www.karger.com/Article/FullText/503926 |
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