Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun 11;19(6):e0304105.
doi: 10.1371/journal.pone.0304105. eCollection 2024.

Association of urinary excretion rates of uric acid with biomarkers of kidney injury in patients with advanced chronic kidney disease

Antía López Iglesias  1 , Marta Blanco Pardo  1 , Catuxa Rodríguez Magariños  1 , Sonia Pértega  2   3 , Diego Sierra Castro  1 , Teresa García Falcón  1 , Ana Rodríguez-Carmona  1 , Miguel Pérez Fontán  1   4
Affiliations

Association of urinary excretion rates of uric acid with biomarkers of kidney injury in patients with advanced chronic kidney disease

Antía López Iglesias et al. PLoS One. .

Abstract

Background: The potential influence of hyperuricemia on the genesis and progression of chronic kidney disease (CKD) remains controversial. In general, the correlation between blood levels of uric acid (UA) and the rate of progression of CKD is considered to be modest, if any, and the results of relevant trials oriented to disclose the effect of urate-lowering therapies on this outcome have been disappointing. Urinary excretion rates of UA could reflect more accurately the potential consequences of urate-related kidney injury.

Method: Using a cross-sectional design, we investigated the correlation between different estimators of the rates of urinary excretion of UA (total 24-hour excretion, mean urinary concentration, renal clearance and fractional excretion)(main study variables), on one side, and urinary levels of selected biomarkers of kidney injury and CKD progression (DKK3, KIM1, NGAL, interleukin 1b and MCP)(main outcome variables), in 120 patients with advanced CKD (mean glomerular filtration rate 21.5 mL/minute). We took into consideration essential demographic, clinical and analytic variables with a potential confounding effect on the explored correlations (control variables). Spearman's rho correlation and nonlinear generalized additive regression models (GAM) with p-splines smoothers were used for statistical analysis.

Main results: Multivariate analysis disclosed independent correlations between urinary UA concentrations, clearances and fractional excretion rates (but not plasma UA or total 24-hour excretion rates of UA), on one side, and the scrutinized markers. These correlations were more consistent for DKK3 and NGAL than for the other biomarkers. Glomerular filtration rate, proteinuria and treatment with statins or RAA axis antagonists were other independent correlates of the main outcome variables.

Conclusions: Our results support the hypothesis that urinary excretion rates of UA may represent a more accurate marker of UA-related kidney injury than plasma levels of this metabolite, in patients with advanced stages of CKD. Further, longitudinal studies will be necessary, to disclose the clinical significance of these findings.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow diagram of patient recruitment.
Fig 2
Fig 2. Histogram of the distribution of the scrutinized markers of kidney injury.
Fig 3
Fig 3. Smoothing regression showing the relationship between plasma uric acid levels and the selected markers of kidney injury.
Fig 4
Fig 4. Smoothing regression showing the relationship between fractional excretion of uric acid and the selected markers of kidney injury.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Stamp I, Dalbeth N: Urate-lowering therapy for asymptomatic hyperuricemia: a need for caution. Sem Arthritis Rheum 2017; 46: 457–464 - PubMed
    1. Feig DI, Kang DH, Johnson RJ: Uric acid and cardiovascular risk. New Engl J Med 2008; 359: 1811–1821 doi: 10.1056/NEJMra0800885 - DOI - PMC - PubMed
    1. Johnson RJ, Bakris GL, Borghi C, Chonchoi MB, Feldman D, Lanaspa MA, et al.: Hyperuricemia, acute and chronic kidney disease, hypertension and cardiovascular disease: Report of a scientific workshop organized by the NKF. Am J Kidney Dis 2018; 71: 851–865 - PMC - PubMed
    1. Ejaz AA, Nakagawa T, Kanbay M, Kuwabara M, Kumear A, Garcia Arroyo F, et al.: Hyperuricemia in Kidney Disease: A Major Risk Factor for Cardiovascular Events, Vascular Calcification, and Renal Damage. Sem Nephrol 2020; 40: 574–585 - PMC - PubMed
    1. Borghi C, Agnoletti D, Cicero AFG, Lurbe E, Virdis A: Uric acid and hypertension: a review of evidence and future perspectives for the management of cardiovascular risk. Hypertension 2022; 79: 927–1936 doi: 10.1161/HYPERTENSIONAHA.122.17956 - DOI - PubMed