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

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.