A novel method for assessing the renal biopsy specimens using an activatable fluorescent probe

Iyama, Takuji; Takata, Tomoaki; Yamada, Kentaro; Mae, Yukari; Taniguchi, Shuji; Ida, Ayami; Ogawa, Masaya; Yamamoto, Michinori; Hamada, Shintaro; Fukuda, Satoshi; Kanda, Tsutomu; Sugihara, Takaaki; Isomoto, Hajime; Urano, Yasuteru

doi:10.1038/s41598-020-69077-w

Cited by 11 publications

(5 citation statements)

References 15 publications

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“…This technique also has a broad application beyond cancers. We recently demonstrated that, based on the abundant expression of GGT in renal proximal tubules, renal biopsy samples could be rapidly evaluated by GGT-HMRG fluorescent probes [ 10 ]. In the present study, urine fluorescence could be detected after GGT-HMRG incubation, and the fluorescence was significantly higher in patients with nephrosclerosis than patients with glomerulonephritis.…”

Section: Discussionmentioning

confidence: 99%

“…Urinary fluorescence imaging, which uses enzyme-activatable fluorescence probes, can be performed even with a conventional digital camera [ 10 ]. Moreover, as the current nephrology practice guidelines emphasize bedside assessments of patients with diabetes and kidney diseases [ 19 ], urinary fluorescence imaging should be considered viable, since it is based on the high sensitivity and rapid fluorescence emissive power of enzyme-activatable fluorescence probes.…”

Section: Discussionmentioning

confidence: 99%

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Fluorescence Imaging Using Enzyme-Activatable Probes for Detecting Diabetic Kidney Disease and Glomerular Diseases

Yamada

Takata

Iyama

et al. 2022

IJMS

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A clear identification of the etiology of glomerular disease is essential in patients with diabetes. Renal biopsy is the gold standard for assessing the underlying nephrotic pathology; however, it has the risk for potential complications. Here, we aimed to investigate the feasibility of urinary fluorescence imaging using an enzyme-activatable probe for differentiating diabetic kidney disease and the other glomerular diseases. Hydroxymethyl rhodamine green (HMRG)-based fluorescent probes targeting gamma-glutamyl transpeptidase (GGT) and dipeptidyl-peptidase (DPP) were used. Urinary fluorescence was compared between groups which were classified by their histopathological diagnoses (diabetic kidney disease, glomerulonephritis, and nephrosclerosis) as obtained by ultrasound-guided renal biopsy. Urinary fluorescence was significantly stronger in patients with diabetic kidney disease compared to those with glomerulonephritis/nephrosclerosis after DPP-HMRG, whereas it was stronger in patients with nephrosclerosis than in patients with glomerulonephritis after GGT-HMRG. Subgroup analyses of the fluorescence performed for patients with diabetes showed consistent results. Urinary fluorescence imaging using enzyme-activatable fluorescence probes thus represents a potential noninvasive assessment technique for kidney diseases in patients with diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fluorescence Imaging Using Enzyme-Activatable Probes for Detecting Diabetic Kidney Disease and Glomerular Diseases

Yamada

Takata

Iyama

et al. 2022

IJMS

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“…Fluorescence images were obtained using a confocal microscope (LSM 780; Carl Zeiss, Osaka, Japan). Fluorescent signal intensities were quantified using the ImageJ software as previously described [ 51 ].…”

Section: Methodsmentioning

confidence: 99%

Uromodulin Regulates Murine Aquaporin−2 Activity via Thick Ascending Limb–Collecting Duct Cross−Talk during Water Deprivation

Takata

Hamada

Mae

et al. 2022

IJMS

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Uromodulin, a urinary protein synthesized and secreted from the thick ascending limb (TAL) of the loop of Henle, is associated with hypertension through the activation of sodium reabsorption in the TAL. Uromodulin is a potential target for hypertension treatment via natriuresis. However, its biological function in epithelial cells of the distal nephron segment, particularly the collecting duct, remains unknown. Herein, we examined the regulation of uromodulin production during water deprivation in vivo as well as the effect of uromodulin on the activity of the water channel aquaporin−2 (AQP2) in vitro and in vivo using transgenic mice. Water deprivation upregulated uromodulin production; immunofluorescence experiments revealed uromodulin adhesion on the apical surface of the collecting duct. Furthermore, the activation of AQP2 was attenuated in mice lacking uromodulin. Uromodulin enhanced the phosphorylation and apical trafficking of AQP2 in mouse collecting duct cells treated with the vasopressin analog dDAVP. The uromodulin-induced apical trafficking of AQP2 was attenuated via endocytosis inhibitor treatment, suggesting that uromodulin activates AQP2 through the suppression of endocytosis. This study provides novel insights into the cross−talk between TAL and the collecting duct, and indicates that the modulation of uromodulin is a promising approach for diuresis and hypertension treatment.

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“…Laboratory studies con rmed that when the concentration of Cd in the body was low, it mainly accumulated in the proximal tubule cells, which are mainly located in the renal cortex. The classical view was that when the concentration of Cd sustained increase approaching to about 150-200 μg/g, a critical threshold, the cells undergo oxidative stress that leads to injury and either necrotic or apoptotic cell death (Iyama et al 2020;Liu et al 2009). The corresponding critical urinary Cd concentration is usually about 2-10 μg/g creatinine (Jarup 2002;Roels et al 1979).…”

Section: Difference Between Glm and Bkmr Model Analysismentioning

confidence: 99%

The association between urine elements and fasting glucose levels in a community-based elderly people in Beijing

Liu

et al. 2022

Environ Sci Pollut Res

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Epidemiological studies have demonstrated that various kinds of urinary element concentrations were different between healthy, prediabetes, and diabetes patients. Meanwhile, many studies have explored the relationship between element concentration and fasting blood glucose (FBG), but the association between joint exposure to co-existing elements and FBG level has not been well understood. The study explored the associations of joint exposure to co-existing urinary elements with FBG level in a crosssectional design. 275 retired elderly people were recruited from Beijing, China. The questionnaire survey was conducted, and biological samples were collected. The generalized linear model (GLM) and twophase Bayesian kernel machine regression (BKMR) model were used to perform in-depth association analysis between urinary elements and FBG. The GLM analysis showed that Zn, Sr, and Cd were signi cantly correlated with the FBG level, under control potential confounding factors. The BKMR analysis demonstrated 8 elements (Zn, Se, Fe, Cr, Ni, Cd, Mn, and Al) had a higher in uence on FBG (Posterior inclusion probabilities >0.1). Further intensive analyses result of the BKMR model indicated that the overall estimated exposure of 8 elements was positively correlated with the FBG level and was statistically signi cant when all element concentrations were at their 65th percentile. Meanwhile, the BKMR analysis showed that Cd and Zn had a statistically signi cant association with FBG levels when other co-existing elements were controlled at different levels (25th, 50th or 75th percentile), respectively.The results of the GLM and BKMR model were inconsistent. The BKMR model could exibly calculate the joint exposure to co-existing elements, evaluate the possible interaction effects and nonlinear correlations. The meaningful conclusions were found that it was di cult to get by traditional methods. This study will provide methodological reference and experimental evidence for the association between joint exposure to co-existing elements and FBG in elderly people. Materials And Methods Research Design and Study PopulationA cross-sectional study design was implemented. The retired elderly people (aged above age 60 or more) recruited from the community-based in Beijing, in 2016. This study was approved by the Ethics Committee of the Institute of Basic Medical Sciences, Peking Union Medical College (Beijing, China), and all participants had signed informed consent before the interviews.Personal information was collected using a structured questionnaire through face-to-face communication by the investigator, including gender, age, smoking status, alcohol drinking status, and body mass index (BMI). Medical records were used to gather information on whether the subjects had diabetes and medication use related to blood sugar control.The vein blood (4 mL) was collected from each subject after overnight fasting and used to measure FBG. Blood samples were collected in vacuum tubes containing a thixotropic gel barrier (BD Vacutainer SST II, REF 367...

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A novel method for assessing the renal biopsy specimens using an activatable fluorescent probe

Cited by 11 publications

References 15 publications

Fluorescence Imaging Using Enzyme-Activatable Probes for Detecting Diabetic Kidney Disease and Glomerular Diseases

Fluorescence Imaging Using Enzyme-Activatable Probes for Detecting Diabetic Kidney Disease and Glomerular Diseases

Uromodulin Regulates Murine Aquaporin−2 Activity via Thick Ascending Limb–Collecting Duct Cross−Talk during Water Deprivation

The association between urine elements and fasting glucose levels in a community-based elderly people in Beijing

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