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Sci Rep. 2019;9(1):14707.

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

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제1저자 안정남, 현진성, 이정표, 황금숙 · 교신저자 이정표, 황금숙

PMID 31605028 PMC6789025 DOI 10.1038/s41598-019-51276-9 IF 4.9 신장내과
소속 (13)
  1. Department of Internal Medicine-Nephrology, Seoul National University Boramae Medical Center, Seoul, Korea.
  2. Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, Korea.
  3. Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
  4. Kidney Research Institute, Seoul National University, Seoul, Korea.
  5. Department of Biostatistics, Seoul National University Boramae Medical Center, Seoul, Korea.
  6. Department of Internal Medicine-Nephrology, Seoul National University Hospital, Seoul, Korea.
  7. Department of Internal Medicine-Nephrology, Kyung Hee University Hospital at Gangdong, Seoul, Korea.
  8. Department of Internal Medicine-Nephrology, Kyungpook National University Hospital, Daegu, Korea.
  9. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
  10. Department of Internal Medicine-Nephrology, Seoul National University Boramae Medical Center, Seoul, Korea. nephrolee@gmail.com.
  11. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. nephrolee@gmail.com.
  12. Integrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, Korea. gshwang@kbsi.re.kr.
  13. Department of Chemistry and Nano Science, Ewha Womans University, Seoul, Korea. gshwang@kbsi.re.kr.

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.

Figures

Figure 1
Figure 1 Multivariate statistical analyses of urine samples from FSGS, MCD and healthy controls. PLS-DA (A) score plot obtained from 1H NMR spectra of urine from FSGS, MCD, and healthy controls. The metabolites exhibiting significant differences in the urine are presented in the loading plot (B). The log-transformed concentration of myo-inositol (μM/mM creatinine) in patients with FSGS was significantly altered compared with both healthy controls and MCD patients in the discovery set (C) and the validation set (D). The data are shown as the median (*P < 0.05, **P < 0.01, ***P < 0.001, comparing healthy controls and FSGS).
Figure 2
Figure 2 Association between urinary myo-inositol and clinical parameters. (A) In the FSGS patients. Log-transformed urinary myo-inositol significantly increased as eGFR decreased (R = −0.682, P < 0.001). Although the association with uPCr was not statistically significant, there was a trend for a positive relationship between uPCr and log-transformed urinary myo-inositol (R = 0.251, P = 0.105). (B) In the MCD patients. There was a weaker association between urinary myo-inositol and eGFR than that in the FSGS patients (R = −0.291, P = 0.009). The relationship with uPCr was not statistically significant (R = 0.160, P = 0.156). (C) Association between suPAR and clinical parameters in FSGS patients. The plasma concentration of suPAR showed a negative relationship with eGFR and a positive relationship with uPCr (R = −0.472, P = 0.001; R = 0.466, P = 0.002). The plasma concentration of suPAR was significantly associated with log-transformed urinary myo-inositol in FSGS patients (R = 0.477, P = 0.001).
Figure 3
Figure 3 Association between urinary myo-inositol and clinical outcomes in the FSGS patients. Although the difference was not significant, the log-transformed urinary myo-inositol level was higher in the nonresponders compared with the responders (nonresponders vs. responders, 2.02 (1.43, 2.06) vs. 1.38 (1.30, 1.61); P = 0.062).
Figure 4
Figure 4 (A) Effect of myo-inositol treatment in the FSGS in vitro model. Administration of recombinant suPAR to podocytes significantly decreased synaptopodin and ZO-1 expression. However, myo-inositol treatment increased the expression of these markers again. These results represent one of three independent experiments. After densitometry analysis of the western blotting results for all cellular protein samples, the results of representative samples are shown in the figure. The data are shown as the mean ± standard deviation and were compared using Student’s t-test (*P < 0.05, **P < 0.01, ***P < 0.001). (B) In FSGS patients, as myo-inositol increased, myo-inositol oxygenase expression significantly decreased. The degree of myo-inositol oxygenase tissue expression was not related to uPCR but was directly proportional to eGFR (***P < 0.001; magnification: 200x).

그림 출처: PubMed Central 공개 논문 (PMC6789025)

Conflict of interest statement

The authors declare no competing interests.

그 밖의 정보
출판 형태
Journal Article, Research Support, Non-U.S. Gov't
저널
Scientific reports · eISSN 2045-2322
전자 출판
2019-10-11
MeSH
Adult · Aged · Biomarkers / urine · Cell Line · Female · Glomerular Filtration Rate · Glomerulosclerosis, Focal Segmental / blood / diagnosis / urine · Humans · Inositol / pharmacology / urine · Inositol Oxygenase / metabolism · Kidney / metabolism / pathology · Male · Middle Aged · Nephrosis, Lipoid / urine · Nuclear Magnetic Resonance, Biomolecular · Podocytes / drug effects · Prognosis · Receptors, Urokinase Plasminogen Activator / blood
Substances
Biomarkers · PLAUR protein, human · Receptors, Urokinase Plasminogen Activator · Inositol · Inositol Oxygenase · MIOX protein, human
참고문헌
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