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Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease

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Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. / Sharma, Kumar; Karl, Bethany; Mathew, Anna V; Gangoiti, Jon A; Wassel, Christina L; Saito, Rintaro; Pu, Minya; Sharma, Shoba; You, Young-Hyun; Wang, Lin; Diamond-Stanic, Maggie; Lindenmeyer, Maja T; Forsblom, Carol; Wu, Wei; Ix, Joachim H; Ideker, Trey; Kopp, Jeffrey B; Nigam, Sanjay K; Cohen, Clemens D; Groop, Per-Henrik; Barshop, Bruce A; Natarajan, Loki; Nyhan, William L; Naviaux, Robert K.

In: J AM SOC NEPHROL, Vol. 24, No. 11, 11.2013, p. 1901-12.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sharma, K, Karl, B, Mathew, AV, Gangoiti, JA, Wassel, CL, Saito, R, Pu, M, Sharma, S, You, Y-H, Wang, L, Diamond-Stanic, M, Lindenmeyer, MT, Forsblom, C, Wu, W, Ix, JH, Ideker, T, Kopp, JB, Nigam, SK, Cohen, CD, Groop, P-H, Barshop, BA, Natarajan, L, Nyhan, WL & Naviaux, RK 2013, 'Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease', J AM SOC NEPHROL, vol. 24, no. 11, pp. 1901-12. https://doi.org/10.1681/ASN.2013020126

APA

Sharma, K., Karl, B., Mathew, A. V., Gangoiti, J. A., Wassel, C. L., Saito, R., Pu, M., Sharma, S., You, Y-H., Wang, L., Diamond-Stanic, M., Lindenmeyer, M. T., Forsblom, C., Wu, W., Ix, J. H., Ideker, T., Kopp, J. B., Nigam, S. K., Cohen, C. D., ... Naviaux, R. K. (2013). Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J AM SOC NEPHROL, 24(11), 1901-12. https://doi.org/10.1681/ASN.2013020126

Vancouver

Sharma K, Karl B, Mathew AV, Gangoiti JA, Wassel CL, Saito R et al. Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease. J AM SOC NEPHROL. 2013 Nov;24(11):1901-12. https://doi.org/10.1681/ASN.2013020126

Bibtex

@article{11691797250d48c1a03ffd96d8fc8586,
title = "Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease",
abstract = "Diabetic kidney disease is the leading cause of ESRD, but few biomarkers of diabetic kidney disease are available. This study used gas chromatography-mass spectrometry to quantify 94 urine metabolites in screening and validation cohorts of patients with diabetes mellitus (DM) and CKD(DM+CKD), in patients with DM without CKD (DM-CKD), and in healthy controls. Compared with levels in healthy controls, 13 metabolites were significantly reduced in the DM+CKD cohorts (P≤0.001), and 12 of the 13 remained significant when compared with the DM-CKD cohort. Many of the differentially expressed metabolites were water-soluble organic anions. Notably, organic anion transporter-1 (OAT1) knockout mice expressed a similar pattern of reduced levels of urinary organic acids, and human kidney tissue from patients with diabetic nephropathy demonstrated lower gene expression of OAT1 and OAT3. Analysis of bioinformatics data indicated that 12 of the 13 differentially expressed metabolites are linked to mitochondrial metabolism and suggested global suppression of mitochondrial activity in diabetic kidney disease. Supporting this analysis, human diabetic kidney sections expressed less mitochondrial protein, urine exosomes from patients with diabetes and CKD had less mitochondrial DNA, and kidney tissues from patients with diabetic kidney disease had lower gene expression of PGC1α (a master regulator of mitochondrial biogenesis). We conclude that urine metabolomics is a reliable source for biomarkers of diabetic complications, and our data suggest that renal organic ion transport and mitochondrial function are dysregulated in diabetic kidney disease. ",
keywords = "Adult, Aged, Diabetic Nephropathies, Female, Glomerular Filtration Rate, Humans, Ion Transport, Male, Metabolomics, Middle Aged, Mitochondrial Diseases, Organic Anion Transport Protein 1, Organic Anion Transporters, Sodium-Independent, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Renal Insufficiency, Chronic, Transcription Factors, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.",
author = "Kumar Sharma and Bethany Karl and Mathew, {Anna V} and Gangoiti, {Jon A} and Wassel, {Christina L} and Rintaro Saito and Minya Pu and Shoba Sharma and Young-Hyun You and Lin Wang and Maggie Diamond-Stanic and Lindenmeyer, {Maja T} and Carol Forsblom and Wei Wu and Ix, {Joachim H} and Trey Ideker and Kopp, {Jeffrey B} and Nigam, {Sanjay K} and Cohen, {Clemens D} and Per-Henrik Groop and Barshop, {Bruce A} and Loki Natarajan and Nyhan, {William L} and Naviaux, {Robert K}",
year = "2013",
month = nov,
doi = "10.1681/ASN.2013020126",
language = "English",
volume = "24",
pages = "1901--12",
journal = "J AM SOC NEPHROL",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "11",

}

RIS

TY - JOUR

T1 - Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease

AU - Sharma, Kumar

AU - Karl, Bethany

AU - Mathew, Anna V

AU - Gangoiti, Jon A

AU - Wassel, Christina L

AU - Saito, Rintaro

AU - Pu, Minya

AU - Sharma, Shoba

AU - You, Young-Hyun

AU - Wang, Lin

AU - Diamond-Stanic, Maggie

AU - Lindenmeyer, Maja T

AU - Forsblom, Carol

AU - Wu, Wei

AU - Ix, Joachim H

AU - Ideker, Trey

AU - Kopp, Jeffrey B

AU - Nigam, Sanjay K

AU - Cohen, Clemens D

AU - Groop, Per-Henrik

AU - Barshop, Bruce A

AU - Natarajan, Loki

AU - Nyhan, William L

AU - Naviaux, Robert K

PY - 2013/11

Y1 - 2013/11

N2 - Diabetic kidney disease is the leading cause of ESRD, but few biomarkers of diabetic kidney disease are available. This study used gas chromatography-mass spectrometry to quantify 94 urine metabolites in screening and validation cohorts of patients with diabetes mellitus (DM) and CKD(DM+CKD), in patients with DM without CKD (DM-CKD), and in healthy controls. Compared with levels in healthy controls, 13 metabolites were significantly reduced in the DM+CKD cohorts (P≤0.001), and 12 of the 13 remained significant when compared with the DM-CKD cohort. Many of the differentially expressed metabolites were water-soluble organic anions. Notably, organic anion transporter-1 (OAT1) knockout mice expressed a similar pattern of reduced levels of urinary organic acids, and human kidney tissue from patients with diabetic nephropathy demonstrated lower gene expression of OAT1 and OAT3. Analysis of bioinformatics data indicated that 12 of the 13 differentially expressed metabolites are linked to mitochondrial metabolism and suggested global suppression of mitochondrial activity in diabetic kidney disease. Supporting this analysis, human diabetic kidney sections expressed less mitochondrial protein, urine exosomes from patients with diabetes and CKD had less mitochondrial DNA, and kidney tissues from patients with diabetic kidney disease had lower gene expression of PGC1α (a master regulator of mitochondrial biogenesis). We conclude that urine metabolomics is a reliable source for biomarkers of diabetic complications, and our data suggest that renal organic ion transport and mitochondrial function are dysregulated in diabetic kidney disease.

AB - Diabetic kidney disease is the leading cause of ESRD, but few biomarkers of diabetic kidney disease are available. This study used gas chromatography-mass spectrometry to quantify 94 urine metabolites in screening and validation cohorts of patients with diabetes mellitus (DM) and CKD(DM+CKD), in patients with DM without CKD (DM-CKD), and in healthy controls. Compared with levels in healthy controls, 13 metabolites were significantly reduced in the DM+CKD cohorts (P≤0.001), and 12 of the 13 remained significant when compared with the DM-CKD cohort. Many of the differentially expressed metabolites were water-soluble organic anions. Notably, organic anion transporter-1 (OAT1) knockout mice expressed a similar pattern of reduced levels of urinary organic acids, and human kidney tissue from patients with diabetic nephropathy demonstrated lower gene expression of OAT1 and OAT3. Analysis of bioinformatics data indicated that 12 of the 13 differentially expressed metabolites are linked to mitochondrial metabolism and suggested global suppression of mitochondrial activity in diabetic kidney disease. Supporting this analysis, human diabetic kidney sections expressed less mitochondrial protein, urine exosomes from patients with diabetes and CKD had less mitochondrial DNA, and kidney tissues from patients with diabetic kidney disease had lower gene expression of PGC1α (a master regulator of mitochondrial biogenesis). We conclude that urine metabolomics is a reliable source for biomarkers of diabetic complications, and our data suggest that renal organic ion transport and mitochondrial function are dysregulated in diabetic kidney disease.

KW - Adult

KW - Aged

KW - Diabetic Nephropathies

KW - Female

KW - Glomerular Filtration Rate

KW - Humans

KW - Ion Transport

KW - Male

KW - Metabolomics

KW - Middle Aged

KW - Mitochondrial Diseases

KW - Organic Anion Transport Protein 1

KW - Organic Anion Transporters, Sodium-Independent

KW - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

KW - Renal Insufficiency, Chronic

KW - Transcription Factors

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, U.S. Gov't, Non-P.H.S.

U2 - 10.1681/ASN.2013020126

DO - 10.1681/ASN.2013020126

M3 - SCORING: Journal article

C2 - 23949796

VL - 24

SP - 1901

EP - 1912

JO - J AM SOC NEPHROL

JF - J AM SOC NEPHROL

SN - 1046-6673

IS - 11

ER -