Renal handling of galectin-3 in the general population, chronic heart failure, and hemodialysis

J Am Heart Assoc. 2014 Sep 18;3(5):e000962. doi: 10.1161/JAHA.114.000962.

Abstract

Background: Galectin-3 is a biomarker for prognostication and risk stratification of patients with heart failure (HF). It has been suggested that renal function strongly relates to galectin-3 levels. We aimed to describe galectin-3 renal handling in HF.

Methods and results: In Sprague-Dawley rats, we infused galectin-3 and studied distribution and renal clearance. Furthermore, galectin-3 was measured in urine and plasma of healthy controls, HF patients and hemodialysis patients. To mimic the human situation, we measured galectin-3 before and after the artificial kidney. Infusion in rats resulted in a clear increase in plasma and urine galectin-3. Plasma galectin-3 in HF patients (n=101; mean age 64 years; 93% male) was significantly higher compared to control subjects (n=20; mean age 58 years; 75% male) (16.6 ng/mL versus 9.7 ng/mL, P<0.001), while urinary galectin-3 in HF patients was comparable (28.1 ng/mL versus 35.1 ng/mL, P=0.830). The calculated galectin-3 excretion rate was lower in HF patient (2.3 mL/min [1.5 to 3.4] versus 3.9 mL/min [2.3 to 6.4] in control subjects; P=0.005). This corresponded with a significantly lower fractional excretion of galectin-3 in HF patients (2.4% [1.7 to 3.7] versus 3.0% [1.9 to 5.5]; P=0.018). These differences, however, were no longer significant after correction for age, gender, diabetes, and smoking. HF patients who received diuretics (49%) showed significantly higher aldosterone and galectin-3 levels. Hemodialysis patients (n=105; mean age 63 years; 65% male), without urinary galectin-3 excretion, had strongly increased median plasma galectin-3 levels (70.6 ng/mL).

Conclusions: In this small cross-sectional study, we report that urine levels of galectin-3 are not increased in HF patients, despite substantially increased plasma galectin-3 levels. The impaired renal handling of galectin-3 in patients with HF may explain the described relation between renal function and galectin-3 and may account for the elevated plasma galectin-3 in HF.

Keywords: heart failure; kidney; remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Animals
  • Blood Proteins
  • Case-Control Studies
  • Chronic Disease
  • Cross-Sectional Studies
  • Female
  • Galectin 3 / administration & dosage
  • Galectin 3 / blood
  • Galectin 3 / metabolism*
  • Galectin 3 / pharmacokinetics
  • Galectin 3 / urine
  • Galectins
  • Heart Failure / diagnosis
  • Heart Failure / metabolism*
  • Humans
  • Kidney / metabolism*
  • Kidney / physiopathology
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / metabolism*
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Rats, Sprague-Dawley
  • Renal Dialysis
  • Renal Elimination

Substances

  • Blood Proteins
  • Galectin 3
  • Galectins
  • LGALS3 protein, human