Urinary Galectin-3 as a Novel Biomarker for the Prediction of Renal Fibrosis and Kidney Disease Progression

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.

Fecal and Urinary Adipokines as Disease Biomarkers

“…In fact, human urine and feces contain measurable levels of adiponectin, lipocalin-2, leptin, galectin-3, chemerin and IL-6, with leptin and chemerin levels being relatively low in stool. In regard to their potential to identify disease and its progression, patients with kidney diseases have higher levels of urinary adiponectin, lipocalin-2, leptin, galectin-3 and IL-6 ( Table 1 ) [ 67 , 130 , 156 , 174 , 212 ]. Hence, these adipokines may emerge as biomarkers for the diagnosis and prognosis of kidney diseases.…”

“…Alternatively, the determination of plasma levels of fibrosis markers could be considered. However, they often lack specificity to provide information on organ-specific disease states [ 171 , 174 ]. Hence, the development of urine biomarkers to determine kidney fibrosis may be more appropriate for routine tests in the clinic or research-related and laboratory-based studies.…”

“…A prospective study showed that patients with higher amounts of urinary galectin-3 (≥510.8 pg/mL) compared to those with lower galectin-3 levels (≤354.6 pg/mL) had a 4.6-fold higher risk of kidney disease progression ( Figure 4 ). Furthermore, renal galectin-3 gene expression was positively associated with biomarkers of renal stress, renal fibrosis and kidney dysfunction [ 174 ]. Given its involvement in inflammatory and fibrotic processes, the determination of urinary galectin-3 levels may become a non-invasive biomarker for advanced kidney diseases.…”

Recent Advances in Urinary Peptide and Proteomic Biomarkers in Chronic Kidney Disease: A Systematic Review

“…Urinary Galectin-3 levels were investigated in a prospective cohort of 220 patients who underwent kidney biopsy. High urinary Gal-3 was associated with higher degrees of kidney fibrosis and higher risk of CKD progression (adjusted HR, 4.60; 95% confidence interval, 2.85-7.71) 57 . Endotrophin, a factor released upon collagen VI deposition in the kidney, was tested as a urinary marker for CKD progression and kidney fibrosis in the Renal Impairment in Secondary Care (RIISC) cohort, a prospective observational study of 499 CKD patients.…”

“…As of now, the degree of interstitial fibrosis and tubular atrophy (IFTA) can only be assessed by invasive kidney biopsy which comes along with a number of problems and limitations as outlined above. Several single peptide biomarkers have been proposed for non-invasive estimation of kidney fibrosis 17,40,52,56,57 . In the recent years novel proteomic biomarkers reflecting the level of kidney fibrosis have been generated.…”