Soluble ST2 and Galectin-3 as Predictors of Chronic Kidney Disease Progression and Outcomes

Abstract

Background: Soluble suppression of tumorigenicity-2 (sST2) and galectin-3, novel biomarkers of heart failure and cardiovascular stress, predict cardiovascular events (CVEs) and mortality. However, their relationship with kidney function and adverse outcomes in CKD are uncertain. The purpose of this study was to determine the association between sST2 and galectin-3 with CKD progression and adverse clinical outcomes. Methods: We measured baseline sST2 and galectin-3 levels in the CKD patient cohort at our institution between October 2013 and December 2014. The primary outcome was CKD progression (kidney failure with replacement therapy or ≥50% reduction in estimated glomerular filtration rate from the baseline). The secondary outcome was the composite of CVEs and death. We used a Cox proportional hazards model to evaluate the associations between sST2 and galectin-3 levels, with kidney and clinical outcomes. Results: In total, 352 patients were enrolled in this study. At baseline, log sST2 and galectin-3 were directly associated with the serum creatinine (Cr) and urine protein-to-Cr ratio. Cox regression analysis showed that the baseline log sST2 level independently predicted CKD progression and composite outcome after adjustment for age, sex, smoking, diabetes mellitus, hypertension, cardiovascular disease, renin-angiotensin system blocker, calcium channel blocker, β-blocker, diuretics, antiplatelet agents, anemia, and hypoalbuminemia. The baseline log galectin-3 level was independently associated with CKD progression, but not with the composite outcome after adjustment for confounding variables. Conclusions: Elevated levels of sST2 and galectin-3 are significantly associated with CKD progression, but only sST2 is associated with adverse clinical outcomes.

Serum Galectin-3 Level Is Positively Associated with Endothelial Dysfunction in Patients with Chronic Kidney Disease Stage 3 to 5

“…However, if the injury is persistent or repetitive, galectin-3 might promote inflammation and fibrosis [ 28 ], and the severity of renal fibrosis and tubular injury of renal transplant also depends on galectin-3 expression [ 29 ]. Galectin-3 levels strongly correlated with eGFR decline in the Ludwigshafen Risk and Cardiovascular Health study and were even more markedly elevated in the German Diabetes Mellitus Dialysis study; it could also identify individuals at risk of developing CKD or rapidly losing renal function over time in the general population and patients with CKD or chronic systolic heart failure [ 12 , 13 , 18 , 19 ]. Similarly, the present study revealed that galectin-3 was significantly associated with renal function decline and positively associated with elevated CRP values.…”

“…Galectin-3 is a novel 35 kDa, soluble β-galactoside-binding lectin expressed by epithelial cells, endothelial cells, and macrophages, with multiple biological abilities, including cell proliferation, differentiation, growth, and inflammation; it has also been related to cardiac fibrosis and heart failure and even long-term adverse prognosis of the general population [ 14 ] and patients with chronic heart failure [ 14 , 15 ], DM [ 16 ], or CKD [ 17 , 18 ]. Particularly, plasma galectin-3 correlates with a lower or even rapidly declining estimated glomerular filtration rate (eGFR) [ 13 , 19 ].…”

Emerging biomarkers for the detection of cardiovascular diseases

“…Over the last decade, more research has revealed that soluble ST2 is substantially more significant in people with heart failure and can aid with risk assessment for both acute and chronic heart failure. The US Food and Drug Administration recently approved a commercialgrade soluble ST2 assay (Presage, Critical Diagnostics, San Diego, CA) for use in chronic heart failure prognosis [49,178,179].…”

Galectin-3 in Kidney Diseases: From an Old Protein to a New Therapeutic Target

“…In another cohort including patients with chronic kidney disease, Gal-3 plasma levels were associated with elevated serum creatinine, urine protein/creatinine ratio, and were independently associated with CKD progression [ 93 ].…”