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Metabolomics

, 14:84 | Cite as

Urine metabolites are associated with glomerular lesions in type 2 diabetes

  • Pierre-Jean Saulnier
  • Manjula Darshi
  • Kevin M. Wheelock
  • Helen C. Looker
  • Gudeta D. Fufaa
  • William C. Knowler
  • E. Jennifer Weil
  • Stephanie K. Tanamas
  • Kevin V. Lemley
  • Rintaro Saito
  • Loki Natarajan
  • Robert G. NelsonEmail author
  • Kumar Sharma
Original Article

Abstract

Introduction

Little is known about the association of urine metabolites with structural lesions in persons with diabetes.

Objectives

We examined the relationship between 12 urine metabolites and kidney structure in American Indians with type 2 diabetes.

Methods

Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan, and included a kidney biopsy at the end of the treatment period. Metabolites were measured in urine samples collected within a median of 6.5 months before the research biopsy. Associations of the creatinine-adjusted urine metabolites with kidney structural variables were examined by Pearson’s correlations and multivariable linear regression after adjustment for age, sex, diabetes duration, hemoglobin A1c, mean arterial pressure, glomerular filtration rate (iothalamate), and losartan treatment.

Results

Participants (n = 62, mean age 45 ± 10 years) had mean ± standard deviation glomerular filtration rate of 137 ± 50 ml/min and median (interquartile range) urine albumin:creatinine ratio of 34 (14–85) mg/g near the time of the biopsy. Urine aconitic and glycolic acids correlated positively with glomerular filtration surface density (partial r = 0.29, P = 0.030 and r = 0.50, P < 0.001) and total filtration surface per glomerulus (partial r = 0.32, P = 0.019 and r = 0.43, P = 0.001). 2-ethyl 3-OH propionate correlated positively with the percentage of fenestrated endothelium (partial r = 0.32, P = 0.019). Citric acid correlated negatively with mesangial fractional volume (partial r=-0.36, P = 0.007), and homovanillic acid correlated negatively with podocyte foot process width (partial r=-0.31, P = 0.022).

Conclusions

Alterations of urine metabolites may associate with early glomerular lesions in diabetic kidney disease.

Keywords

Metabolites Biomarkers Kidney structure Type 2 Diabetes 

Notes

Acknowledgements

The authors thank the participants and the doctors, nurses, and support staff for their role in collecting and processing the data. Portions of this work were presented in abstract form at the 2016 ADA scientific meeting in New Orleans, LA.

Author Contributions

PJS, MD, GDF, HCL, WCK, LN, RGN, and KS designed the study, KMW, EJW, and RGN collected the samples, MD, KMW, EJW, KVL, RGN, and KS performed the measurements, RGN and KS supervised the measurements, PJS, MD, KMW, HCL, GDF, WCK, SKT, RS, LN, RGN, and KS analyzed the data, RGN, HCL, WCK, and KS supervised the project, and all authors contributed to the paper.

Funding

This research was supported by the Intramural Research Program at the National Institute of Diabetes and Digestive and Kidney Diseases and by the American Diabetes Association (Clinical Science Award 1-08-CR-42).

Compliance with ethical standards

Conflict of interest

Pierre-Jean Saulnier, Manjula Darshi, Kevin M. Wheelock, Helen C. Looker, Gudeta D. Fufaa, William C. Knowler, E. Jennifer Weil, Stephanie K. Tanamas, Kevin V. Lemley, Rintaro Saito, Loki Natarajan, Robert G. Nelson, and Kumar Sharma declare that they have no conflict of interest.

Ethical approval

This study was approved by the Institutional Review Board of the National Institute of Diabetes and Digestive and Kidney Diseases. All procedures involving human participants were in accordance with the ethical standards of the Institutional Review Board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11306_2018_1380_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 16 KB)

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Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply  2018

Authors and Affiliations

  • Pierre-Jean Saulnier
    • 1
    • 2
  • Manjula Darshi
    • 3
  • Kevin M. Wheelock
    • 1
  • Helen C. Looker
    • 1
  • Gudeta D. Fufaa
    • 1
  • William C. Knowler
    • 1
  • E. Jennifer Weil
    • 1
  • Stephanie K. Tanamas
    • 1
  • Kevin V. Lemley
    • 4
  • Rintaro Saito
    • 3
  • Loki Natarajan
    • 3
  • Robert G. Nelson
    • 1
    • 5
    Email author
  • Kumar Sharma
    • 3
  1. 1.Phoenix Epidemiology and Clinical Research BranchNational Institute of Diabetes and Digestive and Kidney DiseasesPhoenixUSA
  2. 2.Clinical Investigation Center CIC1402CHU Poitiers, University of Poitiers, INSERMPoitiersFrance
  3. 3.University of California San DiegoSan DiegoUSA
  4. 4.University of Southern CaliforniaLos AngelesUSA
  5. 5.National Institutes of HealthPhoenixUSA

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