Prediction of Declining Renal Function and Albuminuria in Patients With Type 2 Diabetes by Metabolomics
Context: Renal disease in type 2 diabetes mellitus (T2DM) is associated with excess morbidity/mortality. Although estimated glomerular filtration rate (eGFR) and albuminuria are routine for assessing renal impairment, novel biomarkers could improve risk stratification and prediction. Objective: To i...
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Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2016-02, Vol.101 (2), p.696-704 |
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Sprache: | eng |
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Zusammenfassung: | Context:
Renal disease in type 2 diabetes mellitus (T2DM) is associated with excess morbidity/mortality. Although estimated glomerular filtration rate (eGFR) and albuminuria are routine for assessing renal impairment, novel biomarkers could improve risk stratification and prediction.
Objective:
To identify specific biomarkers of progression of renal dysfunction.
Design:
Prospective observational.
Setting:
Academic diabetes clinics.
Patients:
A total of 286 T2DM patients (age, 62 ± 8 y; glycosylated hemoglobin, 7.2 ± 0.9%; eGFR, 85 ± 20 mL · min−1 · 1.73 m2).
Interventions:
None.
Main Outcome Measures:
Progression of eGFR and albuminuria.
Results:
We performed screening metabolomics in serum and urine samples by gas chromatography/mass spectroscopy (MS) and ultra-high performance liquid chromatography/MS/MS. Biomarker identification was performed by random forest using an eGFR cutoff of < 60 mL · min−1 · 1.73 m2 or an albumin/creatinine ratio (ACR) cutoff ≥ 30 mg/g as response variables. At follow-up, eGFR had declined by 16 [9] (median [interquartile ratio]) mL · min−1 · 1.73 m2, and ACR had increased by 41 [135] mg/g in patients in the respective top quartile of changes from baseline. Clinical parameters (gender, age, fasting glucose, and baseline eGFR) predicted outcome, with receiver operator characteristics curve (ROC) = 0.671. The five serum metabolites best correlated with either eGFR < 60 or ACR ≥ 30 at baseline were tested for their ability to improve clinical prediction. The sum of C-glycosyl tryptophan, pseudouridine, and N-acetylthreonine (MetIndex) raised the ROC to 0.739 (P < .0001). eGFR decline was predicted by the top MetIndex quartile (odds ratio = 5.48 [95% confidence interval, 2.23–14.47]). MetIndex also predicted an ACR increase with an odds ratio of 2.82 [1.20–7.03] and a ROC of 0.750. Top urine metabolites did not add significant predictivity.
Conclusions:
A limited number of circulating intermediates of amino acid and nucleotide pathways carry clinically significant predictivity for deterioration of renal function in well-controlled T2DM. |
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ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jc.2015-3345 |