Urinary myo-inositol is associated with the clinical outcome in focal segmental glomerulosclerosis

Jung Nam An; Jin Seong Hyeon; Youngae Jung; Young Wook Choi; Jin Hyuk Kim; Seung Hee Yang; Sohee Oh; Soie Kwon; Sang Ho Lee; Jang Hee Cho; Sun Hee Park; Hunjoo Ha; Dong Ki Kim; Jung Pyo Lee; Geum Sook Hwang

doi:10.1038/s41598-019-51276-9

Urinary myo-inositol is associated with the clinical outcome in focal segmental glomerulosclerosis

Jung Nam An, Jin Seong Hyeon, Youngae Jung, Young Wook Choi, Jin Hyuk Kim, Seung Hee Yang, Sohee Oh, Soie Kwon, Sang Ho Lee, Jang Hee Cho, Sun Hee Park, Hunjoo Ha, Dong Ki Kim, Jung Pyo Lee, Geum Sook Hwang

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) have similar initial histological findings; however, their prognoses are distinct. Therefore, it is of great importance to discriminate FSGS from MCD in the early phase of disease and predict clinical prognosis. A discovery set of 184 urine samples (61 healthy control, 80 MCD, and 43 FSGS) and a validation set of 61 urine samples (12 healthy control, 26 MCD, and 23 FSGS) were collected at the time of kidney biopsy. Metabolic profiles were examined using nuclear magnetic resonance spectroscopy. Of 70 urinary metabolites, myo-inositol was significantly higher in FSGS patients than in control patients (discovery set, 2.34-fold, P < 0.001; validation set, 2.35-fold, P = 0.008) and MCD patients (discovery set, 2.48-fold, P = 0.002; validation set, 1.69-fold, P = 0.042). Myo-inositol showed an inverse relationship with the initial estimated glomerular filtration rate (eGFR) and was associated with the plasma level of soluble urokinase-type plasminogen activator receptor in FSGS patients. Myo-inositol treatment ameliorated the decreased expression of ZO-1 and synaptopodin in an in vitro FSGS model, and as myo-inositol increased, myo-inositol oxygenase tissue expression decreased proportionally to eGFR. Furthermore, urinary myo-inositol exhibited an increase in the power to discriminate FSGS patients, and its addition could better predict the response to initial treatment. In conclusion, urinary myo-inositol may be an important indicator in the diagnosis and treatment of FSGS patients.

Original language	English
Article number	14707
Journal	Scientific Reports
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41598-019-51276-9
State	Published - 1 Dec 2019

Bibliographical note

Funding Information:
This work was supported by a multidisciplinary research grant-in-aid from the Seoul National University Boramae Medical Center (02-2018-2) and by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT of Korea (2017M3A9C4065961 and 2017M3A9D5A01052449), and Korea Basic Science Institute (C39923). The funders had no roles in the study design, in the collection, analysis, or interpretation of the data, in the preparation of the manuscript, or in the decision to submit the article for publication. The biospecimens for this study were provided by the Seoul National University Hospital Human Biobank, a member of the Korea Biobank Network, which is supported by the Ministry of Health and Welfare. All samples derived from the National Biobank of Korea were obtained with informed consent under institutional review board-approved protocols.

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© 2019, The Author(s).

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@article{e27efe90b6d24a1bb809620f1d1f7a3a,

title = "Urinary myo-inositol is associated with the clinical outcome in focal segmental glomerulosclerosis",

abstract = "Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) have similar initial histological findings; however, their prognoses are distinct. Therefore, it is of great importance to discriminate FSGS from MCD in the early phase of disease and predict clinical prognosis. A discovery set of 184 urine samples (61 healthy control, 80 MCD, and 43 FSGS) and a validation set of 61 urine samples (12 healthy control, 26 MCD, and 23 FSGS) were collected at the time of kidney biopsy. Metabolic profiles were examined using nuclear magnetic resonance spectroscopy. Of 70 urinary metabolites, myo-inositol was significantly higher in FSGS patients than in control patients (discovery set, 2.34-fold, P < 0.001; validation set, 2.35-fold, P = 0.008) and MCD patients (discovery set, 2.48-fold, P = 0.002; validation set, 1.69-fold, P = 0.042). Myo-inositol showed an inverse relationship with the initial estimated glomerular filtration rate (eGFR) and was associated with the plasma level of soluble urokinase-type plasminogen activator receptor in FSGS patients. Myo-inositol treatment ameliorated the decreased expression of ZO-1 and synaptopodin in an in vitro FSGS model, and as myo-inositol increased, myo-inositol oxygenase tissue expression decreased proportionally to eGFR. Furthermore, urinary myo-inositol exhibited an increase in the power to discriminate FSGS patients, and its addition could better predict the response to initial treatment. In conclusion, urinary myo-inositol may be an important indicator in the diagnosis and treatment of FSGS patients.",

author = "An, {Jung Nam} and Hyeon, {Jin Seong} and Youngae Jung and Choi, {Young Wook} and Kim, {Jin Hyuk} and Yang, {Seung Hee} and Sohee Oh and Soie Kwon and Lee, {Sang Ho} and Cho, {Jang Hee} and Park, {Sun Hee} and Hunjoo Ha and Kim, {Dong Ki} and Lee, {Jung Pyo} and Hwang, {Geum Sook}",

note = "Funding Information: This work was supported by a multidisciplinary research grant-in-aid from the Seoul National University Boramae Medical Center (02-2018-2) and by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT of Korea (2017M3A9C4065961 and 2017M3A9D5A01052449), and Korea Basic Science Institute (C39923). The funders had no roles in the study design, in the collection, analysis, or interpretation of the data, in the preparation of the manuscript, or in the decision to submit the article for publication. The biospecimens for this study were provided by the Seoul National University Hospital Human Biobank, a member of the Korea Biobank Network, which is supported by the Ministry of Health and Welfare. All samples derived from the National Biobank of Korea were obtained with informed consent under institutional review board-approved protocols. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41598-019-51276-9",

language = "English",

volume = "9",

journal = "Scientific Reports",

issn = "2045-2322",

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T1 - Urinary myo-inositol is associated with the clinical outcome in focal segmental glomerulosclerosis

AU - An, Jung Nam

AU - Hyeon, Jin Seong

AU - Jung, Youngae

AU - Choi, Young Wook

AU - Kim, Jin Hyuk

AU - Yang, Seung Hee

AU - Oh, Sohee

AU - Kwon, Soie

AU - Lee, Sang Ho

AU - Cho, Jang Hee

AU - Park, Sun Hee

AU - Ha, Hunjoo

AU - Kim, Dong Ki

AU - Lee, Jung Pyo

AU - Hwang, Geum Sook

N1 - Funding Information: This work was supported by a multidisciplinary research grant-in-aid from the Seoul National University Boramae Medical Center (02-2018-2) and by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT of Korea (2017M3A9C4065961 and 2017M3A9D5A01052449), and Korea Basic Science Institute (C39923). The funders had no roles in the study design, in the collection, analysis, or interpretation of the data, in the preparation of the manuscript, or in the decision to submit the article for publication. The biospecimens for this study were provided by the Seoul National University Hospital Human Biobank, a member of the Korea Biobank Network, which is supported by the Ministry of Health and Welfare. All samples derived from the National Biobank of Korea were obtained with informed consent under institutional review board-approved protocols. Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) have similar initial histological findings; however, their prognoses are distinct. Therefore, it is of great importance to discriminate FSGS from MCD in the early phase of disease and predict clinical prognosis. A discovery set of 184 urine samples (61 healthy control, 80 MCD, and 43 FSGS) and a validation set of 61 urine samples (12 healthy control, 26 MCD, and 23 FSGS) were collected at the time of kidney biopsy. Metabolic profiles were examined using nuclear magnetic resonance spectroscopy. Of 70 urinary metabolites, myo-inositol was significantly higher in FSGS patients than in control patients (discovery set, 2.34-fold, P < 0.001; validation set, 2.35-fold, P = 0.008) and MCD patients (discovery set, 2.48-fold, P = 0.002; validation set, 1.69-fold, P = 0.042). Myo-inositol showed an inverse relationship with the initial estimated glomerular filtration rate (eGFR) and was associated with the plasma level of soluble urokinase-type plasminogen activator receptor in FSGS patients. Myo-inositol treatment ameliorated the decreased expression of ZO-1 and synaptopodin in an in vitro FSGS model, and as myo-inositol increased, myo-inositol oxygenase tissue expression decreased proportionally to eGFR. Furthermore, urinary myo-inositol exhibited an increase in the power to discriminate FSGS patients, and its addition could better predict the response to initial treatment. In conclusion, urinary myo-inositol may be an important indicator in the diagnosis and treatment of FSGS patients.

AB - Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) have similar initial histological findings; however, their prognoses are distinct. Therefore, it is of great importance to discriminate FSGS from MCD in the early phase of disease and predict clinical prognosis. A discovery set of 184 urine samples (61 healthy control, 80 MCD, and 43 FSGS) and a validation set of 61 urine samples (12 healthy control, 26 MCD, and 23 FSGS) were collected at the time of kidney biopsy. Metabolic profiles were examined using nuclear magnetic resonance spectroscopy. Of 70 urinary metabolites, myo-inositol was significantly higher in FSGS patients than in control patients (discovery set, 2.34-fold, P < 0.001; validation set, 2.35-fold, P = 0.008) and MCD patients (discovery set, 2.48-fold, P = 0.002; validation set, 1.69-fold, P = 0.042). Myo-inositol showed an inverse relationship with the initial estimated glomerular filtration rate (eGFR) and was associated with the plasma level of soluble urokinase-type plasminogen activator receptor in FSGS patients. Myo-inositol treatment ameliorated the decreased expression of ZO-1 and synaptopodin in an in vitro FSGS model, and as myo-inositol increased, myo-inositol oxygenase tissue expression decreased proportionally to eGFR. Furthermore, urinary myo-inositol exhibited an increase in the power to discriminate FSGS patients, and its addition could better predict the response to initial treatment. In conclusion, urinary myo-inositol may be an important indicator in the diagnosis and treatment of FSGS patients.

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U2 - 10.1038/s41598-019-51276-9

DO - 10.1038/s41598-019-51276-9

M3 - Article

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AN - SCOPUS:85073150931

SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 14707

ER -

Urinary myo-inositol is associated with the clinical outcome in focal segmental glomerulosclerosis

Abstract

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