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

Research output: Contribution to journalArticle

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 languageEnglish
Article number14707
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2019

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Focal Segmental Glomerulosclerosis
Inositol
Lipoid Nephrosis
Glomerular Filtration Rate
Inositol Oxygenase
Urine
Urokinase Plasminogen Activator Receptors
Metabolome
Magnetic Resonance Spectroscopy
Therapeutics
Kidney
Biopsy

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An, J. N., Hyeon, J. S., Jung, Y., Choi, Y. W., Kim, J. H., Yang, S. H., ... Hwang, G. S. (2019). Urinary myo-inositol is associated with the clinical outcome in focal segmental glomerulosclerosis. Scientific Reports, 9(1), [14707]. https://doi.org/10.1038/s41598-019-51276-9
An, Jung Nam ; Hyeon, Jin Seong ; Jung, Youngae ; Choi, Young Wook ; Kim, Jin Hyuk ; Yang, Seung Hee ; Oh, Sohee ; Kwon, Soie ; Lee, Sang Ho ; Cho, Jang Hee ; Park, Sun Hee ; Ha, Hunjoo ; Kim, Dong Ki ; Lee, Jung Pyo ; Hwang, Geum Sook. / Urinary myo-inositol is associated with the clinical outcome in focal segmental glomerulosclerosis. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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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}",
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An, JN, Hyeon, JS, Jung, Y, Choi, YW, Kim, JH, Yang, SH, Oh, S, Kwon, S, Lee, SH, Cho, JH, Park, SH, Ha, H, Kim, DK, Lee, JP & Hwang, GS 2019, 'Urinary myo-inositol is associated with the clinical outcome in focal segmental glomerulosclerosis', Scientific Reports, vol. 9, no. 1, 14707. https://doi.org/10.1038/s41598-019-51276-9

Urinary myo-inositol is associated with the clinical outcome in focal segmental glomerulosclerosis. / An, Jung Nam; Hyeon, Jin Seong; Jung, Youngae; Choi, Young Wook; Kim, Jin Hyuk; Yang, Seung Hee; Oh, Sohee; Kwon, Soie; Lee, Sang Ho; Cho, Jang Hee; Park, Sun Hee; Ha, Hunjoo; Kim, Dong Ki; Lee, Jung Pyo; Hwang, Geum Sook.

In: Scientific Reports, Vol. 9, No. 1, 14707, 01.12.2019.

Research output: Contribution to journalArticle

TY - JOUR

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

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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