Urine metabolites are associated with glomerular lesions in type 2 diabetes
- 229 Downloads
Little is known about the association of urine metabolites with structural lesions in persons with diabetes.
We examined the relationship between 12 urine metabolites and kidney structure in American Indians with type 2 diabetes.
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.
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).
Alterations of urine metabolites may associate with early glomerular lesions in diabetic kidney disease.
KeywordsMetabolites Biomarkers Kidney structure Type 2 Diabetes
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.
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.
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.
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 was obtained from all individual participants included in the study.
- Inoki, K. (2008). Role of TSC-mTOR pathway in diabetic nephropathy. Diabetes research and clinical practice, 82(Suppl 1), S59-S62.Google Scholar
- Li, M., Wang, X., Aa, J., Qin, W., Zha, W., Ge, Y., 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. American Journal of Physiology-Renal Physiology, 304, F1317-F1324.Google Scholar
- Moriya, T., Suzuki, Y., Inomata, S., Iwano, M., Kanauchi, M., & Haneda, M. (2014). Renal histological heterogeneity and functional progress in normoalbuminuric and microalbuminuric Japanese patients with type 2 diabetes. BMJ Open Diabetes Research and Care, 2, e000029.CrossRefPubMedPubMedCentralGoogle Scholar
- Pluznick, J. L., Protzko, R. J., Gevorgyan, H., Peterlin, Z., Sipos, A., Han, J., et al. (2013). Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proceedings of the National Academy of Sciences USA, 110, 4410–4415.CrossRefGoogle Scholar
- Saulnier, P. J., Wheelock, K. M., Howell, S., Weil, E. J., Tanamas, S. K., Knowler, W. C., et al. (2017). Advanced Glycation End-Products Predict Loss of Renal Function and Correlate with Lesions of Diabetic Kidney Disease in American Indians with Type 2 Diabetes. Diabetes, 65, 3744–3753.CrossRefGoogle Scholar
- Wong, J., Piceno, Y. M., Desantis, T. Z., Pahl, M., Andersen, G. L., & Vaziri, N. D. (2014). Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD. American Journal of Nephrology, 39, 230–237.CrossRefPubMedPubMedCentralGoogle Scholar