An overview of renal metabolomics.
The high-throughput, high-resolution phenotyping enabled by metabolomics has been applied increasingly to a variety of questions in nephrology research. This article provides an overview of current metabolomics methodologies and nomenclature, citing specific considerations in sample preparation, metabolite measurement, and data analysis that investigators should understand when examining the literature or designing a study. Furthermore, we review several notable findings that have emerged in the literature that both highlight some of the limitations of current profiling approaches, as well as outline specific strengths unique to metabolomics. More specifically, we review data on the following: (i) tryptophan metabolites and chronic kidney disease onset, illustrating the interpretation of metabolite data in the context of established biochemical pathways; (ii) trimethylamine-N-oxide and cardiovascular disease in chronic kidney disease, illustrating the integration of exogenous and endogenous inputs to the blood metabolome; and (iii) renal mitochondrial function in diabetic kidney disease and acute kidney injury, illustrating the potential for rapid translation of metabolite data for diagnostic or therapeutic aims. Finally, we review future directions, including the need to better characterize interperson and intraperson variation in the metabolome, pool existing data sets to identify the most robust signals, and capitalize on the discovery potential of emerging nontargeted methods.
Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts, USA.
Sahir
S
Kalim
Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts, USA; Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA. Electronic address: eprhee@partners.org.
Eugene P
EP
Rhee
D058186:Acute Kidney Injury / Q000097:blood / Q000378:metabolism*; D053000:Analytic Sample Preparation Methods; D002318:Cardiovascular Diseases / Q000097:blood / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics / Q000379:methods* / Q000639:trends; D008744:Methylamines / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
D008744:Methylamines; D014364:Tryptophan; C005855:trimethyloxamine
acute kidney injury; chronic kidney disease; uremia; uremic toxins
J Proteome Res. 2015 Jul 2;14(7):2897-905
26036910
PLoS One. 2015 May 04;10(5):e0126048
25938230
Nat Biotechnol. 2012 Sep;30(9):826-8
22965049
PLoS One. 2014 Feb 24;9(2):e89728
24586991
J Am Coll Cardiol. 2014 Nov 4;64(18):1908-14
25444145
Am J Physiol Cell Physiol. 2015 Jun 1;308(11):C890-8
25810260
Nat Med. 2013 Apr;19(4):407-9
23558627
J Am Soc Nephrol. 2013 Jul;24(8):1330-8
23687356
Semin Nephrol. 2016 Jan;36(1):8-16
27085731
J Am Soc Nephrol. 2016 Jul;27(7):2148-55
26614381
J Proteomics Bioinform. 2015 Oct;Suppl 14:
26778897
J Am Soc Nephrol. 2010 Jun;21(6):1041-1051
20378825
Clin Chem. 2012 Jan;58(1):139-47
22110018
J Clin Invest. 1981 Feb;67(2):563-8
7007440
Nature. 2016 Mar 24;531(7595):528-32
26982719
PLoS One. 2014 Sep 05;9(9):e106647
25191961
Cell. 2014 Oct 9;159(2):318-32
25303528
Cell. 2016 Feb 25;164(5):884-95
26919427
Nature. 2006 Jan 26;439(7075):484-9
16400329
Biol Pharm Bull. 2013;36(4):682-5
23546298
Anal Chem. 2011 Sep 1;83(17):6689-97
21766834
PLoS One. 2016 Jan 11;11(1):e0141738
26751065
J Clin Invest. 1980 May;65(5):1162-73
7364943
Am J Physiol Renal Physiol. 2015 Sep 15;309(6):F492-8
26155843
J Am Soc Nephrol. 2016 Apr;27(4):1175-88
26449609
Oncotarget. 2015 May 30;6(15):13371-86
25945836
Kidney Int. 2014 May;85(5):1214-24
24429397
Nature. 2004 May 13;429(6988):188-93
15141213
Nat Rev Mol Cell Biol. 2012 Mar 22;13(4):263-9
22436749
Circ Res. 2015 Jan 30;116(3):448-55
25599331
Metabolomics. 2005 Mar;1(1):3-9
16680201
J Am Soc Nephrol. 2016 Oct;27(10):2997-3004
27056296
Nat Med. 2010 Mar;16(3):279-85
20190767
J Ren Nutr. 2015 Jul;25(4):351-6
25802017
Xenobiotica. 1987 May;17(5):551-8
3604260
Am J Nephrol. 2016;43(5):366-74
27172772
Clin J Am Soc Nephrol. 2014 Jan;9(1):37-45
24235289
J Am Heart Assoc. 2016 Mar 15;5(3):e002712
27068627
Mol Cell. 2015 May 21;58(4):699-706
26000853
Am J Kidney Dis. 2010 Aug;56(2):348-58
20605303
Am J Physiol Renal Physiol. 2008 Jul;295(1):F226-34
18480171
Cancer Res. 2015 Jun 15;75(12):2541-52
25952651
J Clin Invest. 1963 Feb;42:263-76
13940831
Nature. 2014 May 8;509(7499):183-8
24670636
PLoS One. 2015 Dec 09;10(12):e0143731
26650937
J Am Heart Assoc. 2013 Dec 05;2(6):e000542
24308938
J Biol Chem. 2006 Aug 4;281(31):22021-22028
16754668
Nephrol Dial Transplant. 2013 Aug;28(8):2131-8
23739151
J Am Soc Nephrol. 2016 Jan;27(1):305-13
26229137
Cell. 2016 Mar 24;165(1):111-124
26972052
Nucleic Acids Res. 2013 Jan;41(Database issue):D801-7
23161693
Nat Commun. 2015 Jan 23;6:6001
25613188
Clin J Am Soc Nephrol. 2013 Mar;8(3):363-70
23220422
Clin J Am Soc Nephrol. 2014 Aug 7;9(8):1410-7
25011442
Am J Transplant. 2014 Oct;14(10):2339-49
25138024
Nature. 2011 Apr 7;472(7341):57-63
21475195
J Am Soc Nephrol. 2017 Jan;28(1):321-331
27436853
Biomed Chromatogr. 2014 Sep;28(9):1235-45
24619916
Clin J Am Soc Nephrol. 2014 Apr;9(4):690-7
24436478
Curr Diab Rep. 2016 Jul;16(7):61
27155611
J Am Soc Nephrol. 2011 Sep;22(9):1769-76
21784895
J Am Soc Nephrol. 2013 Nov;24(11):1901-12
23949796
Kidney Int. 2016 May;89(5):1144-1152
27083288
J Am Soc Nephrol. 2016 Feb;27(2):466-81
26203118
Nat Med. 2013 May;19(5):576-85
23563705
N Engl J Med. 2013 Apr 25;368(17):1575-84
23614584
Diabetes. 2015 Mar;64(3):718-32
25713200