Abstract
The kidneys are critical for the secretion of cytokines and hormones, the excretion of waste metabolites, and the homeostasis of electrolytes. Chronic kidney disease (CKD) is a major epidemiologic problem and a risk factor for cardiovascular events and cerebrovascular accidents. At present, renal function is generally evaluated by measuring estimated glomerular filtration rate (eGFR). However, this method has low sensitivity during the early stages of CKD. A new biomarker that can detect CKD during its early stages is eagerly awaited: mass spectrometry (MS), an effective technology for the discovery of biomarkers due to its high sensitivity to detect many compounds, seems to fit these conditions.
Metabolomics using mass spectrometry is a powerful strategy for profiling metabolites and can be used to effectively explore unknown compounds that change in abundance with respect to disease condition. Recently, many researchers have endeavored to apply metabolomics techniques to diagnose various diseases, including CKD. Some metabolites that can serve as biomarkers for CKD severity have been discovered, thanks to their efforts.
This chapter reviews metabolomics techniques and their potential to be applied to CKD diagnosis.
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Abbreviations
- CE-MS:
-
Capillary electrophoresis-mass spectrometry
- CKD:
-
Chronic kidney disease
- CysC:
-
Cystatin C
- DMSO:
-
Dimethyl sulfoxide
- ESRD:
-
End-stage renal disease
- FT-ICR-MS:
-
Fourier transform-ion cyclotron resonance-mass spectrometry
- GC-MS:
-
Gas chromatography-mass spectrometry
- GFR:
-
Glomerular filtration rate
- HMDB:
-
Human metabolome database
- KEGG:
-
Kyoto encyclopedia of genes and genomes
- LC-MS:
-
Liquid chromatography-mass spectrometry
- MS/MS:
-
Tandem mass spectrometry
- PLS:
-
Partial least squares
- SFC-MS:
-
Supercritical fluid chromatography-mass spectrometry
- TOC:
-
Total organic carbon
- TOF-MS:
-
Time-of-flight-mass spectrometry
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Definitions
- Chronic kidney disease (CKD) and glomerular filtration rate (GFR)
-
CKD is defined by the following two criteria. (1) Kidney damage confirmed by urine tests, imaging tests, and blood tests. Especially, albuminuria is a typical symptom. (2) Reduced glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 over 3 months.
CKD is classified into six stages according to GFR (see table below) (Levey et al. 2011). Stage 1 and Stage 2 do not equate to CKD if kidney damage is not comorbid. Stage 5 is equivalent to end-stage renal disease.
GFR (mL/min/1.73 m2)
CKD stage
90>
1
60–89
2
45–59
3a
30–44
3b
15–29
4
15<
5
- Estimated glomerular filtration rate (eGFR)
-
Since direct measurements of GFR are invasive and time-consuming, GFR is typically estimated using blood creatinine, age, and gender. There are various formulas for calculating eGFR: the Cockcroft–Gault equation, the Modification of Diet in Renal Disease (MDRD) Study equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the Japanese Society of Nephrology Chronic Kidney Disease Initiative (JSN-CKDI) equation, and so on. Because blood creatinine is proportional to the muscle mass, the formula used differs depending on the patient’s race and gender.
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Kobayashi, T. (2015). Metabolomics and Stages of Chronic Kidney Disease. In: Patel, V. (eds) Biomarkers in Kidney Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7743-9_41-1
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DOI: https://doi.org/10.1007/978-94-007-7743-9_41-1
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