Abstract
Background/aims
In diabetic patients, reduced urinary pH (UpH) is a predictive factor for cardiorenal-vascular disorders. Synthesis of glutathione, an anti-oxidative stress substance, is induced to counteract renal oxidative stress. UpH declines as glutamate is consumed, as does the synthesis of ammonia from glutamate. Glutathione is synthesized from glutamate and cysteine; however, in diabetes, the relationship between lowered UpH and the roles of renal amino acids is unknown. We, therefore, examined the relationship between amino-acid kinetics, UpH, and renal function.
Methods
This cross-sectional study targeted 100 non-diabetic obese individuals (OG: obese group) and 100 diabetics (DG: diabetic group). We investigated their blood amino acids, urinary amino-acid excretion, the reabsorption rates of various amino acids, and their relationship with the UpH and estimated glomerular filtration rate (eGFR).
Results
The DG subjects showed higher blood cysteine concentration, urinary glutamate, and cysteine excretions than the OG subjects. Although the glutamate reabsorption rate declined in the DG subjects, that of cysteine increased due to the lowered eGFR. The DG subjects’ urinary cysteine excretion correlated positively with UpH, making this urinary cysteine excretion the sole independent risk factor for lower UpH.
Conclusion
In patients with diabetes, the reabsorbed amount of cysteine, not glutamate, regulates the amount of glutathione synthesis in the kidneys. The more an amount of cysteine reabsorption increases concurrently with a decline in eGFR, the more its urinary excretion decreases. Under these conditions, concurrently, the glutamate consumption then increases, resulting in decreased ammonia synthesis and UpH.
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Acknowledgements
The authors wish to thank Miss Asako Chiba and Mrs. Yasuko Sato for their assistance with gathering the urine samples for the study. We also wish to thank nurses Eiko Mitsui, Yoko Hasegawa, Michiko Ota, Megumi Ito, and Hiromi Sato for their efforts in gathering student data. Our deep appreciation goes to all members of the staff who helped us in this study.
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This work was supported by Tohoku University’s Center for the Advancement of Higher Education President’s Research Fund.
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All the authors have declared no competing interest.
Research involving human participants and/or animals
Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number: 2015-1-139) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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SO wrote the manuscript and researched the data, while MS, JT, KN, MO, and MK contributed to the collection of samples, the discussion, and researched the data. SI reviewed and edited the manuscript.
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Ogawa, S., Takiguchi, J., Shimizu, M. et al. The relationship between the renal reabsorption of cysteine and the lowered urinary pH in diabetics. Clin Exp Nephrol 21, 1044–1052 (2017). https://doi.org/10.1007/s10157-017-1401-1
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DOI: https://doi.org/10.1007/s10157-017-1401-1