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

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

doi:10.1038/s41598-019-51276-9

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.

Highlights

Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) have similar initial histological findings; their prognoses are distinct
We reported urinary metabolite profiles of FSGS patients compared to those of MCD patients or healthy controls, and we found a significant difference in urinary myo-inositol levels among these groups
Urinary myo-inositol levels were significantly related to the clinical parameters of FSGS patients measured at diagnosis and increased the ability to distinguish FSGS patients from MCD patients compared to traditional clinical parameters

Summary

Introduction

Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) have similar initial histological findings; their prognoses are distinct. 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. Urinary myo-inositol exhibited an increase in the power to discriminate FSGS patients, and its addition could better predict the response to initial treatment. Several studies have shown that soluble urokinase plasminogen-type activator receptor (suPAR) levels increase in primary FSGS2, there are reports that it is associated with decreased renal function rather than FSGS itself. The biopsy results of FSGS are confused with minimal change disease (MCD); MCD is diagnosed initially, but FSGS is often diagnosed in a subsequent biopsy. Correspondence and requests for materials should be addressed to J.P.L.

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Conclusion