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Erschienen in: Acta Diabetologica 11/2018

01.09.2018 | Original Article

Optimization of kidney dysfunction prediction in diabetic kidney disease using targeted metabolomics

verfasst von: Isabel Ibarra-González, Ivette Cruz-Bautista, Omar Yaxmehen Bello-Chavolla, Marcela Vela-Amieva, Rigoberto Pallares-Méndez, Diana Ruiz de Santiago Y Nevarez, María Fernanda Salas-Tapia, Ximena Rosas-Flota, Mayela González-Acevedo, Adriana Palacios-Peñaloza, Mario Morales-Esponda, Carlos Alberto Aguilar-Salinas, Laura del Bosque-Plata

Erschienen in: Acta Diabetologica | Ausgabe 11/2018

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Abstract

Aims

Metabolomics have been used to evaluate the role of small molecules in human disease. However, the cost and complexity of the methodology and interpretation of findings have limited the transference of knowledge to clinical practice. Here, we apply a targeted metabolomics approach using samples blotted in filter paper to develop clinical-metabolomics models to detect kidney dysfunction in diabetic kidney disease (DKD).

Methods

We included healthy controls and subjects with type 2 diabetes (T2D) with and without DKD and investigated the association between metabolite concentrations in blood and urine with eGFR and albuminuria. We also evaluated performance of clinical, biochemical and metabolomic models to improve kidney dysfunction prediction in DKD.

Results

Using clinical-metabolomics models, we identified associations of decreased eGFR with body mass index (BMI), uric acid and C10:2 levels; albuminuria was associated to years of T2D duration, A1C, uric acid, creatinine, protein intake and serum C0, C10:2 and urinary C12:1 levels. DKD was associated with age, A1C, uric acid, BMI, serum C0, C10:2, C8:1 and urinary C12:1. Inclusion of metabolomics increased the predictive and informative capacity of models composed of clinical variables by decreasing Akaike’s information criterion, and was replicated both in training and validation datasets.

Conclusions

Targeted metabolomics using blotted samples in filter paper is a simple, low-cost approach to identify outcomes associated with DKD; the inclusion of metabolomics improves predictive capacity of clinical models to identify kidney dysfunction and DKD-related outcomes.
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Literatur
1.
Zurück zum Zitat American Diabetes Association (2001) Clinical practice recommendations 2001: diabetic nephropathy (position statement). Diabetes Care 24(suppl):S69–S72 American Diabetes Association (2001) Clinical practice recommendations 2001: diabetic nephropathy (position statement). Diabetes Care 24(suppl):S69–S72
2.
Zurück zum Zitat Giorda CB, Carnà P, Salomone M, et al (2018) Ten-year comparative analysis of incidence, prognosis, and associated factors for dialysis and renal transplantation in type 1 and type 2 diabetes versus non-diabetes. Acta Diabetol 55(7):733–740CrossRef Giorda CB, Carnà P, Salomone M, et al (2018) Ten-year comparative analysis of incidence, prognosis, and associated factors for dialysis and renal transplantation in type 1 and type 2 diabetes versus non-diabetes. Acta Diabetol 55(7):733–740CrossRef
3.
Zurück zum Zitat Penno G, Solini A, Bonora E, Renal Insufficiency Events C (RIACE) Study Group, et al (2018) Defining the contribution of chronic kidney disease to all-cause mortality in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. Acta Diabetol 55(6):603–612CrossRef Penno G, Solini A, Bonora E, Renal Insufficiency Events C (RIACE) Study Group, et al (2018) Defining the contribution of chronic kidney disease to all-cause mortality in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study. Acta Diabetol 55(6):603–612CrossRef
4.
Zurück zum Zitat Mora-Fernández C, Domínguez-Pimentel V, de Fuentes MM, Górriz JL, et al (2014) Diabetic kidney disease: from physiology to therapeutics. J Physiol 592(18):3997–4012CrossRef Mora-Fernández C, Domínguez-Pimentel V, de Fuentes MM, Górriz JL, et al (2014) Diabetic kidney disease: from physiology to therapeutics. J Physiol 592(18):3997–4012CrossRef
5.
Zurück zum Zitat Zhang J, Wang Y, Gurung P, et al (2018) The relationship between the thickness of glomerular basement membrane and renal outcomes in patients with diabetic nephropathy. Acta Diabetol 55(7):669–679CrossRef Zhang J, Wang Y, Gurung P, et al (2018) The relationship between the thickness of glomerular basement membrane and renal outcomes in patients with diabetic nephropathy. Acta Diabetol 55(7):669–679CrossRef
6.
Zurück zum Zitat Susztak K, Böttinger EP (2006) Diabetic nephropathy: a frontier for personalized medicine. J Am Soc Nephrol 17(2):361–367CrossRef Susztak K, Böttinger EP (2006) Diabetic nephropathy: a frontier for personalized medicine. J Am Soc Nephrol 17(2):361–367CrossRef
7.
Zurück zum Zitat Urbschat A, Obermüller N, Haferkamp A (2011) Biomarkers of kidney injury. Biomarkers 16(Suppl 1):S22–S30CrossRef Urbschat A, Obermüller N, Haferkamp A (2011) Biomarkers of kidney injury. Biomarkers 16(Suppl 1):S22–S30CrossRef
9.
Zurück zum Zitat Suhre K, Meisinger C, Döring A, Altmaier E, Belcredi P, Gieger C et al (2010) Metabolic footprint of diabetes: a multiplatform metabolomics study in an epidemiological setting. PLoS One 5(11):e13953CrossRef Suhre K, Meisinger C, Döring A, Altmaier E, Belcredi P, Gieger C et al (2010) Metabolic footprint of diabetes: a multiplatform metabolomics study in an epidemiological setting. PLoS One 5(11):e13953CrossRef
10.
Zurück zum Zitat Fiehn O, Garvey WT, Newman JW, Lok KH, Hoppel CL, Adams SH (2010) Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African–American women. PLoS One 5(12):e15234CrossRef Fiehn O, Garvey WT, Newman JW, Lok KH, Hoppel CL, Adams SH (2010) Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African–American women. PLoS One 5(12):e15234CrossRef
11.
Zurück zum Zitat Floegel A, Stefan N, Yu Z, Mühlenbruch K, Drogan D, Joost HG et al (2013) Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach. Diabetes 62(2):639–648CrossRef Floegel A, Stefan N, Yu Z, Mühlenbruch K, Drogan D, Joost HG et al (2013) Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach. Diabetes 62(2):639–648CrossRef
12.
Zurück zum Zitat Niewczas MA, Sirich TL, Mathew AV, Skupien J, Mohney RP, Warram JH et al (2014) Uremic solutes and risk of end-stage renal disease in type 2 diabetes: metabolomic study. Kidney Int 85(5):1214–1224CrossRef Niewczas MA, Sirich TL, Mathew AV, Skupien J, Mohney RP, Warram JH et al (2014) Uremic solutes and risk of end-stage renal disease in type 2 diabetes: metabolomic study. Kidney Int 85(5):1214–1224CrossRef
13.
Zurück zum Zitat Li M, Wang X, Aa J, et al (2013) GC/TOFMS analysis of metabolites in serum and urine reveals metabolic perturbation of TCA cycle in db/db mice involved in diabetic nephropathy. Am J Physiol Renal Physiol 304(11):F1317–F1324CrossRef Li M, Wang X, Aa J, et al (2013) GC/TOFMS analysis of metabolites in serum and urine reveals metabolic perturbation of TCA cycle in db/db mice involved in diabetic nephropathy. Am J Physiol Renal Physiol 304(11):F1317–F1324CrossRef
14.
Zurück zum Zitat Solini A, Manca ML, Penno G, Pugliese G, Cobb JE, Ferrannini E (2016) Prediction of declining renal function and albuminuria in patients with type 2 diabetes by metabolomics. J Clin Endocrinol Metab 101(2):696–704CrossRef Solini A, Manca ML, Penno G, Pugliese G, Cobb JE, Ferrannini E (2016) Prediction of declining renal function and albuminuria in patients with type 2 diabetes by metabolomics. J Clin Endocrinol Metab 101(2):696–704CrossRef
16.
Zurück zum Zitat Wang TJ, Larson MG, Vasan RS, et al (2011) Metabolite profiles and the risk of developing diabetes. Nat Med 17(4):448–453CrossRef Wang TJ, Larson MG, Vasan RS, et al (2011) Metabolite profiles and the risk of developing diabetes. Nat Med 17(4):448–453CrossRef
17.
Zurück zum Zitat Chace DH, Kalas TA, Naylor EW (2003) Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns. Clin Chem 49(11):1797–1817CrossRef Chace DH, Kalas TA, Naylor EW (2003) Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns. Clin Chem 49(11):1797–1817CrossRef
18.
Zurück zum Zitat Arreola-Guerra JM, Rincón-Pedrero R, Cruz-Rivera C, Belmont-Pérez T, Correa-Rotter R, Niño-Cruz JA (2014) Performance of MDRD-IDMS and CKD-EPI equations in Mexican individuals with normal renal function. Nefrologia 34(5):591–598PubMed Arreola-Guerra JM, Rincón-Pedrero R, Cruz-Rivera C, Belmont-Pérez T, Correa-Rotter R, Niño-Cruz JA (2014) Performance of MDRD-IDMS and CKD-EPI equations in Mexican individuals with normal renal function. Nefrologia 34(5):591–598PubMed
19.
Zurück zum Zitat Teruel Briones JL, Gomis Couto A, Sabater J, et al (2011) Validation of the chronic kidney disease epidemiology collaboration (CKD-EPI) equation in advanced chronic renal failure. Nefrologia 31(6):677–682PubMed Teruel Briones JL, Gomis Couto A, Sabater J, et al (2011) Validation of the chronic kidney disease epidemiology collaboration (CKD-EPI) equation in advanced chronic renal failure. Nefrologia 31(6):677–682PubMed
20.
Zurück zum Zitat Aittokalio T, Schwikowski B (2006) Graph-based methods for analyzing networks in cell biology. Brief Bioinform 7(3):243–255CrossRef Aittokalio T, Schwikowski B (2006) Graph-based methods for analyzing networks in cell biology. Brief Bioinform 7(3):243–255CrossRef
21.
Zurück zum Zitat Han LD, Xia JF, Liang QL, Wang Y, Wang YM, Hu P (2011) Plasma esterified and non-esterified fatty acids metabolic profiling using gas chromatography-mass spectrometry and its application in the study of diabetic mellitus and diabetic nephropathy. Anal Chim Acta 689(1):85–91CrossRef Han LD, Xia JF, Liang QL, Wang Y, Wang YM, Hu P (2011) Plasma esterified and non-esterified fatty acids metabolic profiling using gas chromatography-mass spectrometry and its application in the study of diabetic mellitus and diabetic nephropathy. Anal Chim Acta 689(1):85–91CrossRef
22.
Zurück zum Zitat Hirayama A, Nakashima E, Sugimoto M, et al (2012) Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy. Anal Bioanal Chem 404(10):3101–3109CrossRef Hirayama A, Nakashima E, Sugimoto M, et al (2012) Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy. Anal Bioanal Chem 404(10):3101–3109CrossRef
23.
Zurück zum Zitat Mäkinen VP, Kangas AJ, Soininen P, Würtz P, Groop PH, Ala-Korpela M (2013) Metabolic phenotyping of diabetic nephropathy. Clin Pharmacol Ther 94(5):566–569CrossRef Mäkinen VP, Kangas AJ, Soininen P, Würtz P, Groop PH, Ala-Korpela M (2013) Metabolic phenotyping of diabetic nephropathy. Clin Pharmacol Ther 94(5):566–569CrossRef
24.
Zurück zum Zitat Lanza IR, Zhang S, Ward LE, Karakelides H, Raftery D, Nair KS (2010) Quantitative metabolomics by H-NMR and LC–MS/MS confirms altered metabolic pathways in diabetes. PLoS One 5(5):e10538CrossRef Lanza IR, Zhang S, Ward LE, Karakelides H, Raftery D, Nair KS (2010) Quantitative metabolomics by H-NMR and LC–MS/MS confirms altered metabolic pathways in diabetes. PLoS One 5(5):e10538CrossRef
25.
Zurück zum Zitat Pena MJ, Lambers Heerspink HJ, Hellemons ME, Friedrich T, Dallmann G, Lajer M (2014) Urine and plasma metabolites predict the development of diabetic nephropathy in individuals with type 2 diabetes mellitus. Diabet Med 31(9):1138–1147CrossRef Pena MJ, Lambers Heerspink HJ, Hellemons ME, Friedrich T, Dallmann G, Lajer M (2014) Urine and plasma metabolites predict the development of diabetic nephropathy in individuals with type 2 diabetes mellitus. Diabet Med 31(9):1138–1147CrossRef
26.
Zurück zum Zitat Stec DF, Wang S, Stothers C, et al (2015) Alterations of urinary metabolite profile in model diabetic nephropathy. Biochem Biophys Res Commun 456(2):610–614CrossRef Stec DF, Wang S, Stothers C, et al (2015) Alterations of urinary metabolite profile in model diabetic nephropathy. Biochem Biophys Res Commun 456(2):610–614CrossRef
27.
Zurück zum Zitat Zhang J, Wang Y, Zhang R, et al (2018) Implication of decreased serum complement 3 in patients with diabetic nephropathy. Acta Diabetol 55(1):31–39CrossRef Zhang J, Wang Y, Zhang R, et al (2018) Implication of decreased serum complement 3 in patients with diabetic nephropathy. Acta Diabetol 55(1):31–39CrossRef
28.
Zurück zum Zitat Feng G, Gao JL, Zhang P, et al (2017) Decreased serum extracellular superoxide dismutase activity is associated with albuminuria in Chinese patients with type 2 diabetes mellitus. Acta Diabetol 54(11):1047–1055CrossRef Feng G, Gao JL, Zhang P, et al (2017) Decreased serum extracellular superoxide dismutase activity is associated with albuminuria in Chinese patients with type 2 diabetes mellitus. Acta Diabetol 54(11):1047–1055CrossRef
29.
Zurück zum Zitat Qi S, Ouyang X, Wang L, Peng W, Wen J, Dai Y (2012) A pilot metabolic profiling study in serum of patients with chronic kidney disease based on (1) H-NMR-spectroscopy. Clin Transl Sci 5(5):379–385CrossRef Qi S, Ouyang X, Wang L, Peng W, Wen J, Dai Y (2012) A pilot metabolic profiling study in serum of patients with chronic kidney disease based on (1) H-NMR-spectroscopy. Clin Transl Sci 5(5):379–385CrossRef
30.
Zurück zum Zitat Sun J, Shannon M, Ando Y, et al (2012) Serum metabolomic profiles from patients with acute kidney injury: a pilot study. J Chromatogr B Analyt Technol Biomed Life Sci 893:107–113CrossRef Sun J, Shannon M, Ando Y, et al (2012) Serum metabolomic profiles from patients with acute kidney injury: a pilot study. J Chromatogr B Analyt Technol Biomed Life Sci 893:107–113CrossRef
31.
Zurück zum Zitat Goek ON, Döring A, Gieger C, et al (2012) Serum metabolite concentrations and decreased GFR in the general population. Am J Kidney Dis 60(2):197–206CrossRef Goek ON, Döring A, Gieger C, et al (2012) Serum metabolite concentrations and decreased GFR in the general population. Am J Kidney Dis 60(2):197–206CrossRef
32.
Zurück zum Zitat Campion CG, Sanchez-Ferras O, Batchu SN (2017) Potential role of serum and urinary biomarkers in diagnosis and prognosis of diabetic nephropathy. Can J Kidney Health Dis 4:2054358117705371CrossRef Campion CG, Sanchez-Ferras O, Batchu SN (2017) Potential role of serum and urinary biomarkers in diagnosis and prognosis of diabetic nephropathy. Can J Kidney Health Dis 4:2054358117705371CrossRef
33.
Zurück zum Zitat You H, Gao T, Cooper TK, Morris SM Jr, Awad AS (2013) Arginase inhibition mediates renal tissue protection in diabetic nephropathy by a nitric oxide synthase 3-dependent mechanism. Kidney Int 84(6):1189–1197CrossRef You H, Gao T, Cooper TK, Morris SM Jr, Awad AS (2013) Arginase inhibition mediates renal tissue protection in diabetic nephropathy by a nitric oxide synthase 3-dependent mechanism. Kidney Int 84(6):1189–1197CrossRef
34.
Zurück zum Zitat Persson P, Fasching A, Teerlink T, Hansell P, Palm F (2014) l-Citrulline, but not l-arginine, prevents diabetes mellitus-induced glomerular hyperfiltration and proteinuria in rat. Hypertension 64(2):323–329CrossRef Persson P, Fasching A, Teerlink T, Hansell P, Palm F (2014) l-Citrulline, but not l-arginine, prevents diabetes mellitus-induced glomerular hyperfiltration and proteinuria in rat. Hypertension 64(2):323–329CrossRef
35.
Zurück zum Zitat Shah VO, Townsend RR, Feldman HI, Pappan KL, Kensicki E, Vander Jagt DL (2013) Plasma metabolomics profiles in different stages of CKD. Clin J Am Soc Nephrol 8(3):363–370CrossRef Shah VO, Townsend RR, Feldman HI, Pappan KL, Kensicki E, Vander Jagt DL (2013) Plasma metabolomics profiles in different stages of CKD. Clin J Am Soc Nephrol 8(3):363–370CrossRef
36.
Zurück zum Zitat Duranton F, Lundin U, Gayrard N, Mischak H, Aparicio M, Mourad G et al (2014) Plasma and urinary amino acid metabolomics profiling in patients with different levels of kidney function. Clin J Am Soc Nephrol 9(1):37–45CrossRef Duranton F, Lundin U, Gayrard N, Mischak H, Aparicio M, Mourad G et al (2014) Plasma and urinary amino acid metabolomics profiling in patients with different levels of kidney function. Clin J Am Soc Nephrol 9(1):37–45CrossRef
37.
Zurück zum Zitat Ahmad S (2001) L-carnitine in dialysis patients. Semin Dial 14(3):209–217CrossRef Ahmad S (2001) L-carnitine in dialysis patients. Semin Dial 14(3):209–217CrossRef
38.
Zurück zum Zitat Wanner C, Förstner-Wanner S, Rössle C, Fürst P, Schollmeyer P, Hörl WH (1987) Carnitine metabolism in patients with chronic renal failure: effect of l-carnitine supplementation. Kidney Int Suppl 22:S132–S135PubMed Wanner C, Förstner-Wanner S, Rössle C, Fürst P, Schollmeyer P, Hörl WH (1987) Carnitine metabolism in patients with chronic renal failure: effect of l-carnitine supplementation. Kidney Int Suppl 22:S132–S135PubMed
39.
Zurück zum Zitat Nkuipou-Kenfack E, Duranton F, Gayrard N, Argilés À, Lundin U, Weinberger KM, Dakna M et al (2014) Assessment of metabolomics and proteomic biomarkers in detection and prognosis of progression of renal function in chronic kidney disease. PLoS One 9(5):e96955CrossRef Nkuipou-Kenfack E, Duranton F, Gayrard N, Argilés À, Lundin U, Weinberger KM, Dakna M et al (2014) Assessment of metabolomics and proteomic biomarkers in detection and prognosis of progression of renal function in chronic kidney disease. PLoS One 9(5):e96955CrossRef
40.
Zurück zum Zitat Fouque D, Holt S, Guebre-Egziabher F, Nakamura K, Vianey-Saban C, Hadj-Aïssa A et al (2006) Relationship between serum carnitine, acylcarnitines, and renal function in patients with chronic renal disease. J Ren Nutr 16(2):125–131CrossRef Fouque D, Holt S, Guebre-Egziabher F, Nakamura K, Vianey-Saban C, Hadj-Aïssa A et al (2006) Relationship between serum carnitine, acylcarnitines, and renal function in patients with chronic renal disease. J Ren Nutr 16(2):125–131CrossRef
41.
Zurück zum Zitat Atzler D, Schwedhelm E, Zeller T (2014) Integrated genomics and metabolomics in nephrology. Nephrol Dial Transplant 29(8):1467–1474CrossRef Atzler D, Schwedhelm E, Zeller T (2014) Integrated genomics and metabolomics in nephrology. Nephrol Dial Transplant 29(8):1467–1474CrossRef
42.
Zurück zum Zitat van der Kloet FM, Tempels FW, Ismail N, van der Heijden R, Kasper PT, Rojas-Cherto M et al (2012) Discovery of early-stage biomarkers for diabetic kidney disease using ms-based metabolomics (FinnDiane study). Metabolomics 8(1):109–119CrossRef van der Kloet FM, Tempels FW, Ismail N, van der Heijden R, Kasper PT, Rojas-Cherto M et al (2012) Discovery of early-stage biomarkers for diabetic kidney disease using ms-based metabolomics (FinnDiane study). Metabolomics 8(1):109–119CrossRef
43.
Zurück zum Zitat Rebouche CJ (2004 Nov) Kinetics, pharmacokinetics, and regulation of l-carnitine and acetyl-l-carnitine metabolism. Ann NY Acad Sci 1033:30–41CrossRef Rebouche CJ (2004 Nov) Kinetics, pharmacokinetics, and regulation of l-carnitine and acetyl-l-carnitine metabolism. Ann NY Acad Sci 1033:30–41CrossRef
44.
Zurück zum Zitat Rossi C, Marzano V, Consalvo A, et al (2018) Proteomic and metabolomic characterization of streptozotocin-induced diabetic nephropathy in TIMP3-deficient mice. Acta Diabetol 55(2):121–129CrossRef Rossi C, Marzano V, Consalvo A, et al (2018) Proteomic and metabolomic characterization of streptozotocin-induced diabetic nephropathy in TIMP3-deficient mice. Acta Diabetol 55(2):121–129CrossRef
45.
Zurück zum Zitat Hocher B, Adamski J (2017) Metabolomics for clinical use and research in chronic kidney disease. Nat Rev Nephrol 13(5):269–284CrossRef Hocher B, Adamski J (2017) Metabolomics for clinical use and research in chronic kidney disease. Nat Rev Nephrol 13(5):269–284CrossRef
46.
Zurück zum Zitat Chang YH, Hwu DW, Chang DM, An LW, Hsieh CH, Lee YJ (2017) Renal function preservation with pioglitazone or with basal insulin as an add-on therapy for patients with type 2 diabetes mellitus. Acta Diabetol 54(6):561–568CrossRef Chang YH, Hwu DW, Chang DM, An LW, Hsieh CH, Lee YJ (2017) Renal function preservation with pioglitazone or with basal insulin as an add-on therapy for patients with type 2 diabetes mellitus. Acta Diabetol 54(6):561–568CrossRef
47.
Zurück zum Zitat Mei JV, Alexander JR, Adam BW, Hannon WH (2001) Use of filter paper for the collection and analysis of human whole blood specimens. J Nutr 131(5):1631S–1631S6SCrossRef Mei JV, Alexander JR, Adam BW, Hannon WH (2001) Use of filter paper for the collection and analysis of human whole blood specimens. J Nutr 131(5):1631S–1631S6SCrossRef
48.
Zurück zum Zitat McDade TW, Williams S, Snodgrass JJ (2007) What a drop can do: dried blood spots as a minimally invasive method for integrating biomarkers into population-based research. Demography 44(4):899–925CrossRef McDade TW, Williams S, Snodgrass JJ (2007) What a drop can do: dried blood spots as a minimally invasive method for integrating biomarkers into population-based research. Demography 44(4):899–925CrossRef
49.
Zurück zum Zitat Brindle E, O´Connor KA, Garret DA (2014) Applications of dried blood spots in general human health studies. In: Dried blood spots applications and techniques, 1st edn. Wiley, Hoboken, pp 114–129 Brindle E, O´Connor KA, Garret DA (2014) Applications of dried blood spots in general human health studies. In: Dried blood spots applications and techniques, 1st edn. Wiley, Hoboken, pp 114–129
Metadaten
Titel
Optimization of kidney dysfunction prediction in diabetic kidney disease using targeted metabolomics
verfasst von
Isabel Ibarra-González
Ivette Cruz-Bautista
Omar Yaxmehen Bello-Chavolla
Marcela Vela-Amieva
Rigoberto Pallares-Méndez
Diana Ruiz de Santiago Y Nevarez
María Fernanda Salas-Tapia
Ximena Rosas-Flota
Mayela González-Acevedo
Adriana Palacios-Peñaloza
Mario Morales-Esponda
Carlos Alberto Aguilar-Salinas
Laura del Bosque-Plata
Publikationsdatum
01.09.2018
Verlag
Springer Milan
Erschienen in
Acta Diabetologica / Ausgabe 11/2018
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-018-1213-0

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