Galectin-3 is independently associated with progression of nephropathy in type 2 diabetes mellitus

Diabetologia. 2018 May;61(5):1212-1219. doi: 10.1007/s00125-018-4552-z. Epub 2018 Feb 7.

Abstract

Aims/hypothesis: Galectin-3 has been implicated in cardiac and renal fibrosis and serves as a prognostic clinical indicator in heart failure. The aim of the present study was to evaluate whether serum galectin-3 level is associated with progressive kidney disease in type 2 diabetes.

Methods: Galectin-3 was measured in baseline samples by ELISA in 1320 participants with type 2 diabetes with eGFR ≥30 ml min-1 1.73 m-2. The primary outcome was defined as doubling of serum creatinine and/or initiation of renal replacement therapy during follow-up. The secondary outcome was progression to macroalbuminuria in individuals with normo- or microalbuminuria at baseline.

Results: Serum galectin-3 levels were significantly increased in a random subgroup of 270 type 2 diabetic individuals with eGFR >60 ml min-1 1.73 m-2 compared with an age- and sex-matched non-diabetic control group (7.58 ± 2.29 ng/ml vs 6.10 ± 1.91 ng/ml, respectively, p < 0.01). In the whole diabetic cohort, after a mean follow-up of 9 years, galectin-3 was independently associated with doubling of serum creatinine (HR 1.19; 95% CI 1.14, 1.24, p < 0.001) and incident macroalbuminuria (HR 1.20; 95% CI 1.12, 1.30, p < 0.001), even after adjusting for traditional risk factors, baseline eGFR and albuminuria status. Individuals with galectin-3 levels in the highest quartile had a fourfold risk of renal function loss and threefold risk of incident macroalbuminuria.

Conclusions/interpretation: Serum galectin-3 was independently associated with progressive renal disease in type 2 diabetes. Further mechanistic studies are warranted to determine whether galectin-3 is simply a disease biomarker or is also a mediator of the development and progression of diabetic nephropathy.

Keywords: Diabetic nephropathy; Doubling of creatinine; Galectin-3; Incident macroalbuminuria; Renal fibrosis; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / blood
  • Biomarkers / blood
  • Creatinine / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetic Nephropathies / blood*
  • Diabetic Nephropathies / pathology
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Galectin 3 / blood*
  • Glomerular Filtration Rate
  • Humans
  • Kidney Failure, Chronic / blood
  • Male
  • Middle Aged
  • Prognosis
  • Risk Factors

Substances

  • Biomarkers
  • Galectin 3
  • LGALS3 protein, human
  • Creatinine