Abstract
Plasma galectin-3 (Gal-3) is associated with organ fibrosis, but whether urinary Gal-3 is a potential biomarker of kidney disease progression has never been explored. Between 2018 and 2021, we prospectively enrolled 280 patients who underwent renal biopsy and were divided into three groups based on their urinary Gal-3 levels (<354.6, 354.6–510.7, and ≥510.8 pg/mL) to assess kidney disease progression (defined as ≥40% decline in the estimated glomerular filtration rate or end-stage renal disease) and renal histology findings. Patients in the highest urinary Gal-3 tertile had the lowest eGFRs and highest proteinuria levels. In multivariate Cox regression models, patients in the highest tertile had the highest risk of kidney disease progression (adjusted hazard ratio, 4.60; 95% confidence interval, 2.85–7.71) compared to those in the lowest tertile. Higher urinary Gal-3 levels were associated with more severe renal fibrosis. Intrarenal mRNA expression of LGALS3 (Gal-3-encoded gene) was most correlated with the renal stress biomarkers (IGFBP7 and TIMB2), renal function biomarkers (PTGDS) and fibrosis-associated genes (TGFB1). The urinary Gal-3 level may be useful for the identification of patients at high risk of kidney disease progression and renal fibrosis, and for the early initiation of treatments for these patients.
Highlights
Kidney disease progression was defined as ≥40% decline in the estimated glomerular filtration rate (eGFR) from baseline or end-stage renal disease (ESRD) [18,19]
In multivariate Cox regression (Table 2), adjusted hazard ratios with 95% confidence intervals (CIs) for kidney disease progression among patients in the highest and middle
Each 100 pg/mL increase in the urinary Gal-3 levels increased the risks of kidney disease progression
Summary
Chronic kidney disease (CKD) constitutes a global health burden with a rising incidence and prevalence [1]. It may cause renal function decline that progresses to end-stage renal disease (ESRD) [2]. The early identification of patients at greater risk of such decline would allow the prompt initiation of interventions or treatment [3]. As it can be collected non-invasively and is accessible, urine has become an important and useful source of disease biomarkers, especially for early-stage disease [4,5]. Proteinuria is the most reported urinary biomarker of renal function decline, but it may not be ideal for the early detection of this condition because it is accompanied by evident renal damage and lacks sensitivity [6]
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