Serum Myo-Inositol, Dimethyl Sulfone, and Valine in Combination with Creatinine Allow Accurate Assessment of Renal Insufficiency—A Proof of Concept

Ehrich, J. H. H.; Dubourg, Laurence; Hansson, Sverker; Pape, Lars; Steinle, Tobias; Fruth, J. M.; Höckner, Sebastian; Schiffer, Eric

doi:10.3390/diagnostics11020234

Cited by 14 publications

(29 citation statements)

References 52 publications

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“…With this in mind, we recently employed a nuclear magnetic resonance spectroscopy (NMR) based metabolomics approach to identify a ‘metabolite constellation’ (GFR NMR ) to reflect more accurately GFR among individuals with and without chronic kidney disease (CKD). This proof-of-concept study, integrating myo-inositol as marker for reduced filtration, valine as indicator of acid-base metabolism, and dimethyl sulfone as marker of oxidative stress in combination with serum creatinine, allowed accurate assessment of eGFR [ 12 ]. The observed accuracy exceeded that of serum creatinine and of serum cystatin C alone, and matched the accuracy of their combination in pediatric, adolescent, adult, and geriatric patients with various nephrological conditions [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…This proof-of-concept study, integrating myo-inositol as marker for reduced filtration, valine as indicator of acid-base metabolism, and dimethyl sulfone as marker of oxidative stress in combination with serum creatinine, allowed accurate assessment of eGFR [ 12 ]. The observed accuracy exceeded that of serum creatinine and of serum cystatin C alone, and matched the accuracy of their combination in pediatric, adolescent, adult, and geriatric patients with various nephrological conditions [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Estimating Glomerular Filtration Rate from Serum Myo-Inositol, Valine, Creatinine and Cystatin C

Grassi¹,

Meeusen

Lieske

et al. 2021

Diagnostics

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Assessment of renal function relies on the estimation of the glomerular filtration rate (eGFR). Existing eGFR equations, usually based on serum levels of creatinine and/or cystatin C, are not uniformly accurate across patient populations. In the present study, we expanded a recent proof-of-concept approach to optimize an eGFR equation targeting the adult population with and without chronic kidney disease (CKD), based on a nuclear magnetic resonance spectroscopy (NMR) derived ‘metabolite constellation’ (GFRNMR). A total of 1,855 serum samples were partitioned into development, internal validation and external validation datasets. The new GFRNMR equation used serum myo-inositol, valine, creatinine and cystatin C plus age and sex. GFRNMR had a lower bias to tracer measured GFR (mGFR) than existing eGFR equations, with a median bias (95% confidence interval [CI]) of 0.0 (−1.0; 1.0) mL/min/1.73 m2 for GFRNMR vs. −6.0 (−7.0; −5.0) mL/min/1.73 m2 for the Chronic Kidney Disease Epidemiology Collaboration equation that combines creatinine and cystatin C (CKD-EPI2012) (p < 0.0001). Accuracy (95% CI) within 15% of mGFR (1-P15) was 38.8% (34.3; 42.5) for GFRNMR vs. 47.3% (43.2; 51.5) for CKD-EPI2012 (p < 0.010). Thus, GFRNMR holds promise as an alternative way to assess eGFR with superior accuracy in adult patients with and without CKD.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Estimating Glomerular Filtration Rate from Serum Myo-Inositol, Valine, Creatinine and Cystatin C

Grassi¹,

Meeusen

Lieske

et al. 2021

Diagnostics

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Section: Methodsmentioning

confidence: 99%

“…The NMR measurement was carried out at 37 °C after pre-heating of samples at 37 °C for 7.5 min. The acquisition and processing of NMR spectra and the quantification of NMR signals for a lipoprotein subclass and a small metabolite analysis were carried out as described [9,16]. Peripheral blood (5 mL) was drawn in S-Monovette serum tubes (Sarstedt AG, Nümbrecht, Germany) and processed immediately (centrifugation 3000 rpm, 5 min, 4 • C) to collect serum, which was aliquoted and stored at −80 • C until further use.…”

Section: Nmr Axinon ® Platformmentioning

confidence: 99%

“…A standardized NMR platform was shown to be a powerful analytical tool for an in-depth lipoprotein analysis in various contexts [ 9 , 10 , 11 , 12 , 13 ]. Recently, a metabolomic analysis using the same technology and AI-based approaches allowed the identification of constellations of urinary and blood metabolites as novel biomarkers for a non-invasive assessment of a renal allograft rejection [ 14 , 15 ] and the precise estimation of a kidney function [ 16 ], respectively.…”

Section: Introductionmentioning

confidence: 99%

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NMR-Based Lipid Metabolite Profiles to Predict Outcomes in Patients Undergoing Interventional Therapy for a Hepatocellular Carcinoma (HCC): A Substudy of the SORAMIC Trial

Geyer

Rübenthaler

Alunni-Fabbroni

et al. 2021

Cancers

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Background: This exploratory study aimed to evaluate lipidomic and metabolomic profiles in patients with early and advanced HCCs and to investigate whether certain metabolic parameters may predict the overall survival in these patients. Methods: A total of 60 patients from the prospective, randomized-controlled, multicenter phase II SORAMIC trial were included in this substudy; among them were 30 patients with an early HCC who underwent radiofrequency ablation combined with sorafenib or a placebo and 30 patients with an advanced HCC who were treated with a selective internal radiation therapy (SIRT) plus sorafenib vs. sorafenib alone. The blood serum of these patients was analyzed using a standardized nuclear magnetic resonance (NMR) platform. All tested metabolites were correlated with the overall survival. Results: The overall survival (OS) was significantly higher in patients with an early HCC (median OS: 34.0 months) compared with patients with an advanced HCC (median OS: 12.0 months) (p < 0.0001). Patients with high serum concentrations of myo-inositol (MI) had a higher overall survival compared with patients with low concentrations (21.6 vs. 13.8 months) with a Pearson correlation coefficient of 0.331 (p = 0.011). Patients with high serum concentrations of dimethylamine had a higher overall survival compared with patients with low concentrations (25.1 vs. 19.7 months) with a Pearson correlation coefficient of 0.279 (p = 0.034). High concentrations of total cholesterol, LDL-cholesterol and LDL particles (LDL-P) were associated with a decreased overall survival. Conclusions: NMR-based lipidomic and metabolomic profiling has the potential to identify individual metabolite biomarkers that predict the outcome of patients with an HCC exposed to non-invasive therapeutic management.

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Nuclear Magnetic Resonance-Based Metabolomics Approach Revealed the Intervention Effect of Using Complementary and Alternative Medicine (CAM) by CKD Patients

et al. 2023

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Chronic kidney disease (CKD) is the end point of a number of systemic chronic diseases. The prevalence of CKD is increasing worldwide and recent epidemiological studies are showing the high prevalence of renal failure in CKD patients using complementary and alternative medicines (CAMs). Clinicians believe that biochemical profiles of CKD patients using CAM (referred here to as CAM-CKD) may be different compared to those on standard clinical treatment and should be managed differently. The present study aims to explore the potential of the NMR-based metabolomics approach to reveal the serum metabolic disparity between CKD and CAM-CKD patients with respect to normal control (NC) subjects and if the differential metabolic patterns can provide rationale for the efficacy and safety of standard and/or alternative therapies. Serum samples were obtained from 30 CKD patients, 43 CAM-CKD patients, and 47 NC subjects. The quantitative serum metabolic profiles were measured using 1D 1H CPMG NMR experiments performed at 800 MHz NMR spectrometer. The serum metabolic profiles were compared using various multivariate statistical analysis tools available on MetaboAnalyst (freely available web-based software) such as partial least-squares discriminant analysis (PLS-DA) and random forest (a machine learning) classification method. The discriminatory metabolites were identified based on variable importance in projection (VIP) statistics and further evaluated for statistical significance (i.e., p < 0.05) using either Student t-test or ANOVA statistics. PLS-DA models were capable of clustering CKD and CAM-CKD with considerably high values of Q 2 and R 2. Compared to CAM-CKD patients, the sera of CKD patients were characterized by (a) elevated levels of urea, creatinine, citrate, glucose, glycerol, and phenylalanine and phenylalanine-to-tyrosine ratio (PTR) and (b) decreased levels of various amino acids (such leucine, isoleucine, valine, and alanine), high-density lipoproteins, lactate, and acetate. These changes suggested that CKD patients manifest severe oxidative stress, hyperglycemia (with dampened glycolysis), increased protein energy wasting, and reduced lipid/membrane metabolism. Statistically significant and strong positive correlation of PTR with serum creatinine levels suggested the role of oxidative stress in the progression of kidney disease. Significant differences in metabolic patterns between CKD and CAM-CKD patients were observed. With respect to NC subjects, the serum metabolic changes were more aberrant in CKD patients compared to CAM-CKD patients. The aberrant metabolic changes in CKD patients with manifestations of higher oxidative stress compared to CAM-CKD patients could explain clinical discrepancies between CKD and CAM-CKD patients and further advocate the use of different treatment strategies for CKD and CAM-CKD patients.

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Serum Myo-Inositol, Dimethyl Sulfone, and Valine in Combination with Creatinine Allow Accurate Assessment of Renal Insufficiency—A Proof of Concept

Cited by 14 publications

References 52 publications

Estimating Glomerular Filtration Rate from Serum Myo-Inositol, Valine, Creatinine and Cystatin C

Estimating Glomerular Filtration Rate from Serum Myo-Inositol, Valine, Creatinine and Cystatin C

NMR-Based Lipid Metabolite Profiles to Predict Outcomes in Patients Undergoing Interventional Therapy for a Hepatocellular Carcinoma (HCC): A Substudy of the SORAMIC Trial

Nuclear Magnetic Resonance-Based Metabolomics Approach Revealed the Intervention Effect of Using Complementary and Alternative Medicine (CAM) by CKD Patients

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