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

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Uric Acid*/blood ; Uric Acid*/urine ; Biomarkers*/urine ; Biomarkers*/blood ; Renal Insufficiency, Chronic*/urine ; Renal Insufficiency, Chronic*/blood ; Renal Insufficiency, Chronic*/complications; Humans ; Male ; Female ; Middle Aged ; Aged ; Cross-Sectional Studies ; Glomerular Filtration Rate ; Disease Progression ; Adult

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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 López Iglesias et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

J Am Soc Nephrol. 2020 Dec;31(12):2773-2792. (PMID: 32938648)
Semin Nephrol. 2020 Nov;40(6):535-549. (PMID: 33678309)
PLoS One. 2021 Dec 2;16(12):e0260844. (PMID: 34855873)
Hypertension. 2021 Feb;77(2):383-392. (PMID: 33356394)
Am J Kidney Dis. 2018 Jun;71(6):851-865. (PMID: 29496260)
Clin Kidney J. 2023 Jan 10;16(6):928-938. (PMID: 37261000)
Semin Nephrol. 2020 Nov;40(6):600-613. (PMID: 33678314)
Front Physiol. 2020 Dec 16;11:533344. (PMID: 33391006)
Int Urol Nephrol. 2020 May;52(5):923-932. (PMID: 32232720)
Clin Sci (Lond). 2018 May 8;132(9):909-923. (PMID: 29739822)
Am J Kidney Dis. 2018 Dec;72(6):798-810. (PMID: 30177485)
PLoS Med. 2019 Jan 15;16(1):e1002725. (PMID: 30645594)
Am J Kidney Dis. 2008 Sep;52(3):595-605. (PMID: 18725016)
J Hypertens. 2015 Sep;33(9):1729-41; discussion 1741. (PMID: 26136207)
N Engl J Med. 2008 Oct 23;359(17):1811-21. (PMID: 18946066)
Kidney Blood Press Res. 2018;43(4):1310-1321. (PMID: 30099444)
JCI Insight. 2016 Jan 21;1(1):e84916. (PMID: 27699213)
J Am Soc Nephrol. 2022 Sep;33(9):1657-1672. (PMID: 35858701)
Semin Nephrol. 2020 Nov;40(6):564-573. (PMID: 33678311)
Hypertension. 2022 Sep;79(9):1927-1936. (PMID: 35658505)
J Am Soc Nephrol. 2018 Nov;29(11):2722-2733. (PMID: 30279273)
J Urol. 1994 May;151(5):1198-201. (PMID: 8158759)
J Clin Invest. 2021 Feb 1;131(3):. (PMID: 33290282)
PLoS One. 2015 Aug 28;10(8):e0136994. (PMID: 26317775)
N Engl J Med. 2020 Jun 25;382(26):2504-2513. (PMID: 32579811)
Ren Fail. 2020 Nov;42(1):400-404. (PMID: 32349578)
J Clin Invest. 2013 Sep;123(9):4023-35. (PMID: 23979159)
N Engl J Med. 2020 Jun 25;382(26):2493-2503. (PMID: 32579810)
Front Med (Lausanne). 2018 May 31;5:160. (PMID: 29904633)
Semin Arthritis Rheum. 2017 Feb;46(4):457-464. (PMID: 27591828)
Semin Nephrol. 2020 Nov;40(6):574-585. (PMID: 33678312)
Nat Rev Nephrol. 2020 Jul;16(7):422. (PMID: 32313212)
Clin J Am Soc Nephrol. 2015 May 7;10(5):776-83. (PMID: 25717072)
PLoS One. 2016 Dec 1;11(12):e0167334. (PMID: 27907168)

268B43MJ25 (Uric Acid)
0 (Biomarkers)

Date Created: 20240611 Date Completed: 20240611 Latest Revision: 20240613

20240613

PMC11166352

10.1371/journal.pone.0304105

38861521