Renal nitrate clearance in chronic kidney disease
Open accessAbstract
Background Nitric oxide (NO) is rapidly oxidised in humans to nitrite and nitrate, with nitrate being present in much greater abundance. These oxidation products can be recycled back into nitric oxide via a complex entero-salivary pathway, thus preserving NO activity. Approximately 65% of circulating nitrate is excreted in the urine in 48 h, with the excretory pathway of the remainder unknown. The effect of declining renal function on nitrate clearance is unknown METHODS: Forty five subjects, 21 M, 24F, median age 69 (range 27-75 years) with renal function assessed by CKD-EPI eGFR between 9 and 89 ml/min/1.73 m 2 completed the study. Following a 24 h low nitrate diet a microplate spectrophotometric method was employed to measure plasma nitrate concentration and 24 h urinary nitrate excretion were measured to determine renal nitrate clearance. Results There was a strong positive correlation between urinary nitrate clearance and eGFR, (Spearman R = 0.7665, p < 0.0001) with a moderate negative correlation between plasma nitrate concentration and CKD-EPI eGFR, (Spearman's R = -0.37, p = 0.012). There was a trend between fractional excretion of nitrate and CKD-EPI eGFR (ml/min/1.73 m 2) Spearman's R 0.27, p = 0.07 though this did not reach statistical significance. Plasma nitrate concentration and serum creatinine concentration were positively correlated, Spearman's R = 0.39, p = 0.008. Conclusions We have observed a strong positive association between renal nitrate clearance and renal function such that plasma nitrate rises as renal function falls. Fractional excretion of nitrate appears to decline as renal function falls. As such, urinary nitrate excretion is unlikely to be a reliable marker of endogenous NO synthesis in settings where renal function is altered.
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The effectiveness of the nitrate-nitrite-NO pathway may be limited by alterations to the oral microbiome, reduced salivary flow, chronic diseases, polypharmacy and declining renal function, which affect nitrate clearance.
“the effectiveness of this pathway may be limited by alterations to the oral microbiome, reduced salivary flow, chronic diseases, polypharmacy and declining renal function, which affect nitrate clearance [23,222,235,236,237].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [222]
Altered nitrate handling in CKD is indicated by elevated plasma nitrate levels alongside declining eGFR.
“Altered nitrate handling in CKD, as indicated by elevated plasma nitrate levels alongside declining eGFR”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [222]
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- Authors
- Williams, J. K., Smallwood, M. J., Benjamin, N., D'Souza, R. J., Shore, A. C., Winyard, P. G., & Gilchrist, M.
- Affiliations
- University of Exeter (GB)
- Corresponding author
- Gilchrist, M.
- Venue
- Nitric Oxide
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 97
- Pages
- 16-19
- ISSN
- 1089-8603 (ISSN-L)
- OpenAlex
- W3003877880
- Cited by
- 19
- References
- 29
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 1
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Nitric Oxide (publishedVersion)
- PubMed (publishedVersion)
- Open Research Exeter (University of Exeter) (acceptedVersion, cc-by-nc-nd)
- Figshare (submittedVersion, cc-by-nc-nd)
- Funders
- Royal Devon and Exeter NHS Foundation Trust
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Keywords
- chronic kidney disease, urinary nitrate excretion, estimated glomerular filtration rate, nitric oxide metabolism, serum creatinine
- MeSH terms
- Adult, Aged, Female, Glomerular Filtration Rate, Humans, Male, Middle Aged, Nitrates, Renal Insufficiency, Chronic, ErbB Receptors
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