Association of Urine Galectin-3 With Cardiorenal Outcomes in Patients With Heart Failure

• Published in: Journal of cardiac failure 2024-02, Vol.30 (2), p.340-346
• Main Authors: RAO, VEENA S., IVEY-MIRANDA, JUAN B., COX, ZACHARY L., MORENO-VILLAGOMEZ, JULIETA, TESTANI, JEFFREY M.
• Format: Article
• Language: English
• ISSN: 1071-9164; 1532-8414
• DOI: 10.1016/j.cardfail.2023.05.018

•Biomarkers to distinguish pathological cardiorenal dysfunction are needed in HF.•Urine galectin-3 may be more specific to renal fibrosis than plasma galectin-3.•Urine galectin-3 distinguished all-cause mortality risk at equal low eGFR values.•Urine galectin-3 correlated with P3NP, indicating specificity for renal fibrosis.•Urine galectin-3 may distinguish cardiorenal risk profiles. Approaches to distinguishing pathological cardiorenal dysfunction in heart failure (HF) from functional/hemodynamically mediated changes in serum creatinine are needed. We investigated urine galectin-3 as a candidate biomarker of renal fibrosis and a prognostic indicator of cardiorenal dysfunction phenotypes. We measured urine galectin-3 in 2 contemporary HF cohorts: the Yale Transitional Care Clinic (YTCC) cohort (n = 132) and the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial (n = 434). We assessed the association of urine galectin-3 with all-cause mortality in both cohorts and the association with an established marker of renal tissue fibrosis, urinary amino-terminal propeptide of type III procollagen (PIIINP) in TOPCAT. In the YTCC cohort, there was significant effect modification between higher urine galectin-3 and lower estimated glomerular filtration rates (eGFRs) (Pinteraction = 0.046), such that low eGFR levels had minimal prognostic importance if urine galectin-3 levels were low, but they were important and indicated high risk if urine galectin-3 levels were high. Similar observations were noted in the TOPCAT study (Pinteraction = 0.002). In TOPCAT, urine galectin-3 also positively correlated with urine PIIINP at both baseline (r = 0.43; P < 0.001) and at 12 months (r = 0.42; P < 0.001). Urine galectin-3 levels correlated with an established biomarker of renal fibrosis in 2 cohorts and was able to differentiate high- vs low-risk phenotypes of chronic kidney disease in HF. These proof-of-concept results indicate that additional biomarker research to differentiate cardiorenal phenotypes is warranted. [Display omitted]