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

• Published in: PloS one 2024-06, Vol.19 (6), p.e0304105
• Main Authors: López Iglesias, Antía, Blanco Pardo, Marta, Rodríguez Magariños, Catuxa, Pértega, Sonia, Sierra Castro, Diego, García Falcón, Teresa, Rodríguez-Carmona, Ana, Pérez Fontán, Miguel
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Antagonists; Arthritis; Asymptomatic; Biological markers; Biology and Life Sciences; Biomarkers; Biomarkers - blood; Biomarkers - urine; Blood levels; Blood pressure; Care and treatment; Chronic kidney failure; Clinical trials; Comorbidity; Correlation; Correlation analysis; Creatinine; Cross-Sectional Studies; Cytokines; Demographic variables; Diabetes; Disease Progression; Excretion; Female; Glomerular Filtration Rate; Humans; Hypertension; Hyperuricemia; IL-1β; Injuries; Interleukin 1; Interleukins; Kidney diseases; Kidneys; Life sciences; Longitudinal studies; Male; Medicine and Health Sciences; Metabolism; Metabolites; Middle Aged; Multivariate analysis; Patients; Physical Sciences; Plasma; Plasma levels; Proteins; Proteinuria; Regression analysis; Regression models; Renal function; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - complications; Renal Insufficiency, Chronic - urine; Statins; Statistical analysis; Uric acid; Uric Acid - blood; Uric Acid - urine; Urine; Variables
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0304105

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. 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. 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. 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.