Serum Galectin-3 as a diagnostic and discriminatory biomarker for chronic kidney disease: A case-control study

Abstract

Background: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Conventional markers, such as serum creatinine, estimated glomerular filtration rate, and albuminuria, have limited sensitivity for distinguishing among etiologies of advanced chronic kidney disease (CKD) and become abnormal only after substantial nephron loss. Galectin-3 (GAL-3), a beta-galactoside-binding lectin implicated in renal inflammation and fibrosis, has emerged as a candidate biomarker; however, its diagnostic accuracy in distinguishing DKD from non-diabetic CKD in advanced CKD populations remains unclear.

Objective: To quantify serum GAL-3 concentrations in patients with DKD, non-diabetic CKD, and healthy controls, and to evaluate its diagnostic performance in discriminating between these groups in an advanced CKD population.

Materials and methods: A case-control study that enrolled 128 participants: 32 patients with DKD (all with type 2 diabetes mellitus), 32 with non-diabetic CKD (both groups on regular hemodialysis classified as CKD stage 5/end-stage renal disease [ESRD]), and 64 healthy controls. Serum GAL-3 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose, glycated hemoglobin (HbA1c), renal function tests, and serum albumin levels were assessed using an automated analyzer.

Results: Serum GAL-3 concentrations increased progressively from controls (210.04±34.65 ng/mL) to non-diabetic CKD (262.21±3.19 ng/mL) and then to DKD (368.50±67.10 ng/mL, p<0.001). Receiver operating characteristic (ROC) analysis demonstrated very high discrimination in this cohort between DKD and healthy controls area under the curve (AUC=1.00, 95% CI: 0.963-1.000, sensitivity, 100%, specificity, 100%; cutoff, ≥275.77 ng/mL), excellent differentiation of DKD from non-diabetic CKD (AUC=0.987, 95% CI: 0.905-0.999, sensitivity, 84.37%, specificity, 100%), and strong discrimination of all CKD patients from controls (AUC=0.926, 95% CI: 0.866-0.965; sensitivity, 98.44%, specificity, 73.44%). These cutoff values were derived from the same dataset and should be considered exploratory.

Conclusion: Serum GAL-3 demonstrated very high diagnostic accuracy in identifying and stratifying DKD within this cohort of end-stage renal disease patients on hemodialysis. These exploratory findings suggest that GAL-3 may have potential as a discriminatory biomarker in advanced CKD populations; however, prospective validation in larger, independent cohorts including patients with early-stage CKD is warranted before clinical integration can be recommended.