PMID- 26684276 OWN - NLM STAT- MEDLINE DCOM- 20160629 LR - 20221207 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 101 IP - 2 DP - 2016 Feb TI - Prediction of Declining Renal Function and Albuminuria in Patients With Type 2 Diabetes by Metabolomics. PG - 696-704 LID - 10.1210/jc.2015-3345 [doi] AB - 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 m(2)). 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 m(2) 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 m(2), 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. FAU - Solini, Anna AU - Solini A AD - Department of Clinical and Experimental Medicine (A.S., M.L.M., G.Pe., E.F.), and Department of Mathematics (M.L.M.), University of Pisa, 56126 Pisa, Italy; Department of Clinical and Molecular Medicine (G.Pu.), "La Sapienza" University, 00185 Rome, Italy; Metabolon, Inc (J.E.C.), Durham, North Carolina 27713; and National Research Council Institute of Clinical Physiology (E.F.), 56124 Pisa, Italy. FAU - Manca, Maria Laura AU - Manca ML AD - Department of Clinical and Experimental Medicine (A.S., M.L.M., G.Pe., E.F.), and Department of Mathematics (M.L.M.), University of Pisa, 56126 Pisa, Italy; Department of Clinical and Molecular Medicine (G.Pu.), "La Sapienza" University, 00185 Rome, Italy; Metabolon, Inc (J.E.C.), Durham, North Carolina 27713; and National Research Council Institute of Clinical Physiology (E.F.), 56124 Pisa, Italy. FAU - Penno, Giuseppe AU - Penno G AD - Department of Clinical and Experimental Medicine (A.S., M.L.M., G.Pe., E.F.), and Department of Mathematics (M.L.M.), University of Pisa, 56126 Pisa, Italy; Department of Clinical and Molecular Medicine (G.Pu.), "La Sapienza" University, 00185 Rome, Italy; Metabolon, Inc (J.E.C.), Durham, North Carolina 27713; and National Research Council Institute of Clinical Physiology (E.F.), 56124 Pisa, Italy. FAU - Pugliese, Giuseppe AU - Pugliese G AD - Department of Clinical and Experimental Medicine (A.S., M.L.M., G.Pe., E.F.), and Department of Mathematics (M.L.M.), University of Pisa, 56126 Pisa, Italy; Department of Clinical and Molecular Medicine (G.Pu.), "La Sapienza" University, 00185 Rome, Italy; Metabolon, Inc (J.E.C.), Durham, North Carolina 27713; and National Research Council Institute of Clinical Physiology (E.F.), 56124 Pisa, Italy. FAU - Cobb, Jeff E AU - Cobb JE AD - Department of Clinical and Experimental Medicine (A.S., M.L.M., G.Pe., E.F.), and Department of Mathematics (M.L.M.), University of Pisa, 56126 Pisa, Italy; Department of Clinical and Molecular Medicine (G.Pu.), "La Sapienza" University, 00185 Rome, Italy; Metabolon, Inc (J.E.C.), Durham, North Carolina 27713; and National Research Council Institute of Clinical Physiology (E.F.), 56124 Pisa, Italy. FAU - Ferrannini, Ele AU - Ferrannini E AD - Department of Clinical and Experimental Medicine (A.S., M.L.M., G.Pe., E.F.), and Department of Mathematics (M.L.M.), University of Pisa, 56126 Pisa, Italy; Department of Clinical and Molecular Medicine (G.Pu.), "La Sapienza" University, 00185 Rome, Italy; Metabolon, Inc (J.E.C.), Durham, North Carolina 27713; and National Research Council Institute of Clinical Physiology (E.F.), 56124 Pisa, Italy. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20151218 PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Glycated Hemoglobin A) SB - IM MH - Aged MH - Albuminuria/*etiology MH - Diabetes Mellitus, Type 2/*metabolism MH - Diabetic Nephropathies/*metabolism/physiopathology MH - Disease Progression MH - Female MH - Follow-Up Studies MH - Glomerular Filtration Rate MH - Glycated Hemoglobin/analysis MH - Humans MH - Kidney/*physiopathology MH - Male MH - *Metabolomics MH - Middle Aged MH - Predictive Value of Tests MH - Prospective Studies MH - Risk Assessment EDAT- 2015/12/20 06:00 MHDA- 2016/06/30 06:00 CRDT- 2015/12/20 06:00 PHST- 2015/12/20 06:00 [entrez] PHST- 2015/12/20 06:00 [pubmed] PHST- 2016/06/30 06:00 [medline] AID - 10.1210/jc.2015-3345 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2016 Feb;101(2):696-704. doi: 10.1210/jc.2015-3345. Epub 2015 Dec 18.