The diagnostic value of serum concentrations of 2-(α-mannopyranosyl)-l-tryptophan for normal renal function

Yonemura, Katsuhiko; Takahira, Reiko; Yonekawa, Osamu; Wada, Naohiro; Hishida, Akira

doi:10.1111/j.1523-1755.2004.00521.x

Cited by 22 publications

(19 citation statements)

References 16 publications

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“…In support of the latter hypothesis, Yonemura et al documented a higher sensitivity of C-mannosyltryptophan compared with creatinine for the detection of normal renal function. 24 Moreover, the high correlation of C-mannosyltryptophan with both mGFR and eGFRcr as well as the abolished association between C-mannosyltryptophan and incident ESRD upon inclusion of mGFR as a covariate in the AASK study further support C-mannosyltryptophan as a filtration marker.…”

Section: In Light Of the Current Metabolomics Literaturementioning

confidence: 76%

“…Of these 60 ratios, 42 contained the creatinine precursor creatine, and many of the others were ratios of amino acids. The largest P gain was observed for the X-12094/creatine ratio (P gain=6310 24 ), and the largest P gain for a ratio that did not contain creatine was observed for 3-(4-hydroxyphenyl)lactate/ tyrosine (P gain=2310 17 ). After the completion of our study, X-12094 was identified as N1-methyl-2-pyridone-5-carboxamide, which has been proposed as a uremic toxin.…”

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confidence: 96%

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A Metabolome-Wide Association Study of Kidney Function and Disease in the General Population

Sekula

Goek

Quaye

et al. 2016

Journal of the American Society of Nephrology

172

152

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Small molecules are extensively metabolized and cleared by the kidney. Changes in serum metabolite concentrations may result from impaired kidney function and can be used to estimate filtration (e.g., the established marker creatinine) or may precede and potentially contribute to CKD development. Here, we applied a nontargeted metabolomics approach using gas and liquid chromatography coupled to mass spectrometry to quantify 493 small molecules in human serum. The associations of these molecules with GFR estimated on the basis of creatinine (eGFRcr) and cystatin C levels were assessed in #1735 participants in the KORA F4 study, followed by replication in 1164 individuals in the TwinsUK registry. After correction for multiple testing, 54 replicated metabolites significantly associated with eGFRcr, and six of these showed pairwise correlation (r$0.50) with established kidney function measures: C-mannosyltryptophan, pseudouridine, N-acetylalanine, erythronate, myo-inositol, and N-acetylcarnosine. Higher C-mannosyltryptophan, pseudouridine, and O-sulfo-L-tyrosine concentrations associated with incident CKD (eGFRcr ,60 ml/min per 1.73 m 2 ) in the KORA F4 study. In contrast with serum creatinine, C-mannosyltryptophan and pseudouridine concentrations showed little dependence on sex. Furthermore, correlation with measured GFR in 200 participants in the AASK study was 0.78 for both C-mannosyltryptophan and pseudouridine concentration, and highly significant associations of both metabolites with incident ESRD disappeared upon adjustment for measured GFR. Thus, these molecules may be alternative or complementary markers of kidney function. In conclusion, our study provides a comprehensive list of kidney function-associated metabolites and highlights potential novel filtration markers that may help to improve the estimation of GFR. 27: 117527: -118827: , 201627: . doi: 10.1681 Metabolites are small organic molecules involved in both systemic and organ-specific metabolic processes. The kidney receives about 20% of the cardiac output and is one of the most important excretory organs for a wide variety of metabolites, many of which are freely filtered as solutes of small molecular size. In addition, many metabolites are actively secreted into or reabsorbed from the tubular lumen. The kidney also has a role in the generation and metabolism of some metabolites such as amino acids. Changes in blood metabolite J Am Soc Nephrol

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Section: In Light Of the Current Metabolomics Literaturementioning

confidence: 76%

mentioning

confidence: 96%

A Metabolome-Wide Association Study of Kidney Function and Disease in the General Population

Sekula

Goek

Quaye

et al. 2016

Journal of the American Society of Nephrology

172

152

View full text Add to dashboard Cite

show abstract

“…Serum levels of 2-(a-mannopyranosyl)-L-tryptophan have been shown to be a more accurate measure of renal function than serum creatinine concentration, and renal function can be compared in subjects independently of age and muscle mass when 2-(a-mannopyranosyl)-L-tryptophan concentration is measured 22 . In the discovery cohort we find that levels of C-glyTrp are correlated with those of serum creatinine (squared correlation coefficient R 2 = 0.17, P < 0.0001).…”

Section: Resultsmentioning

confidence: 99%

Metabolomic markers reveal novel pathways of ageing and early development in human populations

Menni¹,

Kastenmüller

Petersen³

et al. 2013

International Journal of Epidemiology

249

238

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Background Human ageing is a complex, multifactorial process and early developmental factors affect health outcomes in old age.Methods Metabolomic profiling on fasting blood was carried out in 6055 individuals from the UK. Stepwise regression was performed to identify a panel of independent metabolites which could be used as a surrogate for age. We also investigated the association with birthweight overall and within identical discordant twins and with genome-wide methylation levels.Results We identified a panel of 22 metabolites which combined are strongly correlated with age (R2 = 59%) and with age-related clinical traits independently of age. One particular metabolite, C-glycosyl tryptophan (C-glyTrp), correlated strongly with age (beta = 0.03, SE = 0.001, P = 7.0 × 10−157) and lung function (FEV1 beta = −0.04, SE = 0.008, P = 1.8 × 10−8 adjusted for age and confounders) and was replicated in an independent population (n = 887). C-glyTrp was also associated with bone mineral density (beta = −0.01, SE = 0.002, P = 1.9 × 10−6) and birthweight (beta = −0.06, SE = 0.01, P = 2.5 × 10−9). The difference in C-glyTrp levels explained 9.4% of the variance in the difference in birthweight between monozygotic twins. An epigenome-wide association study in 172 individuals identified three CpG-sites, associated with levels of C-glyTrp (P < 2 × 10−6). We replicated one CpG site in the promoter of the WDR85 gene in an independent sample of 350 individuals (beta = −0.20, SE = 0.04, P = 2.9 × 10−8). WDR85 is a regulator of translation elongation factor 2, essential for protein synthesis in eukaryotes.Conclusions Our data illustrate how metabolomic profiling linked with epigenetic studies can identify some key molecular mechanisms potentially determined in early development that produce long-term physiological changes influencing human health and ageing.

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“…Increased expression of the proteins containing certain forms of C-glycosylated tryptophan in the aortic vessels have been reported in the diabetic rats. (71) C-glycosylated tryptophan also correlates with eGFR. (72)…”

Section: Discussionmentioning

confidence: 99%

Uremic solutes and risk of end-stage renal disease in type 2 diabetes: metabolomic study

Niewczas

Sirich

Mathew

et al. 2014

Kidney International

197

172

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Here we studied plasma metabolomic profiles as determinants of progression to ESRD in patients with Type 2 diabetes (T2D). This nested case-control study evaluated 40 cases who progressed to ESRD during 8-12 years of follow-up and 40 controls who remained alive without ESRD from the Joslin Kidney Study cohort. Controls were matched with cases for baseline clinical characteristics; although controls had slightly higher eGFR and lower levels of urinary albumin excretion than T2D cases. Plasma metabolites at baseline were measured by mass spectrometry-based global metabolomic profiling. Of the named metabolites in the library, 262 were detected in at least 80% of the study patients. The metabolomic platform recognized 78 metabolites previously reported to be elevated in ESRD (uremic solutes). Sixteen were already elevated in the baseline plasma of our cases years before ESRD developed. Other uremic solutes were either not different or not commonly detectable. Essential amino acids and their derivatives were significantly depleted in the cases, whereas certain amino acid-derived acylcarnitines were increased. All findings remained statistically significant after adjustment for differences between study groups in albumin excretion rate, eGFR or HbA1c. Uremic solute differences were confirmed by quantitative measurements. Thus, abnormal plasma concentrations of putative uremic solutes and essential amino acids either contribute to progression to ESRD or are a manifestation of an early stage(s) of the disease process that leads to ESRD in T2D.

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The diagnostic value of serum concentrations of 2-(α-mannopyranosyl)-l-tryptophan for normal renal function

Abstract: The concentration of serum MPT is a more reliable diagnostic parameter than that of serum creatinine as a measure of normal renal function, and renal function can be compared in subjects independently of age and muscle mass when serum MPT concentration is measured.

Cited by 22 publications

References 16 publications

A Metabolome-Wide Association Study of Kidney Function and Disease in the General Population

A Metabolome-Wide Association Study of Kidney Function and Disease in the General Population

Metabolomic markers reveal novel pathways of ageing and early development in human populations

Uremic solutes and risk of end-stage renal disease in type 2 diabetes: metabolomic study

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