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Clinical Utility of LC-MS/MS for Blood Myo-Inositol in Patients with Acute Kidney Injury and Chronic Kidney Disease
Catherine L Omosule1, Connor J Blair1, Elizabeth Herries1
1Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, United States.
Background:
Diagnosing acute kidney injury (AKI) and chronic kidney disease (CKD) relies on creatinine, which lacks optimal diagnostic sensitivity. The kidney-specific proximal tubular enzyme myo-inositol oxygenase (MIOX) catalyzes the conversion of myo-inositol (MI) to D-glucuronic acid. We hypothesized that proximal tubular damage, which occurs in AKI and CKD, will decrease MIOX activity, causing MI accumulation. To explore this, we developed an LC-MS/MS assay to quantify plasma MI and assessed its potential in identifying AKI and CKD patients.
Methods:
MI was quantified in plasma from 3 patient cohorts [normal kidney function (n = 105), CKD (n = 94), and AKI (n = 54)]. The correlations between MI and creatinine were determined using Deming regression and Pearson correlation and the impact of age, sex, and ethnicity on MI concentrations was assessed. Receiver operating characteristic curve analysis was employed to evaluate MI diagnostic performance.
Results:
In volunteers with normal kidney function, the central 95th percentile range of plasma MI concentrations was 16.6 to 44.2 µM. Age, ethnicity, and sex showed minimal influence on MI. Patients with AKI and CKD exhibited higher median MI concentrations [71.1 (25th percentile: 38.2, 75th percentile: 115.4) and 102.4 (77, 139.5) µM], respectively. MI exhibited excellent sensitivity (98.9%) and specificity (100%) for diagnosing CKD. In patients with AKI, MI increased 32.9 (SD 16.8) h before creatinine.
Conclusions:
This study unveils MI as a potential renal biomarker, notably elevated in plasma during AKI and CKD. Plasma MI rises 33 h prior to serum creatinine, enabling early AKI detection. Further validation and exploration of MI quantitation in kidney disease diagnosis is warranted.
Insights
Myo-inositol (MI) shows promise as a novel biomarker for kidney disease. Elevated plasma MI levels are observed in acute kidney injury (AKI) and chronic kidney disease (CKD), with MI detecting AKI earlier than creatinine.
Area of Science:
- Nephrology
- Biomarker Discovery
- Clinical Chemistry
Background:
- Current diagnostics for acute kidney injury (AKI) and chronic kidney disease (CKD) using creatinine have limited sensitivity.
- Myo-inositol oxygenase (MIOX), a kidney-specific enzyme, is involved in myo-inositol (MI) metabolism.
- Proximal tubular damage in AKI and CKD is hypothesized to decrease MIOX activity, leading to MI accumulation.
Purpose of the Study:
- To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for quantifying plasma myo-inositol (MI).
- To assess the potential of plasma MI as a diagnostic biomarker for acute kidney injury (AKI) and chronic kidney disease (CKD).
Main Methods:
- Quantification of plasma MI using LC-MS/MS in three cohorts: normal kidney function (n=105), CKD (n=94), and AKI (n=54).
- Analysis of correlations between MI and creatinine, and the influence of age, sex, and ethnicity on MI concentrations.
- Evaluation of diagnostic performance using receiver operating characteristic (ROC) curve analysis.
Main Results:
- Plasma MI concentrations in healthy individuals ranged from 16.6 to 44.2 µM.
- Patients with AKI and CKD showed significantly higher median plasma MI levels (71.1 µM and 102.4 µM, respectively).
- MI demonstrated high diagnostic accuracy for CKD (98.9% sensitivity, 100% specificity) and detected AKI 32.9 hours before creatinine elevation.
Conclusions:
- Plasma myo-inositol (MI) is a promising novel biomarker for kidney disease, elevated in both AKI and CKD.
- Elevated MI levels precede creatinine increases in AKI, suggesting potential for early detection.
- Further research is warranted to validate and implement MI quantitation in clinical practice for kidney disease diagnosis.
