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Diabetologia

, Volume 61, Issue 5, pp 1212–1219 | Cite as

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

  • Kathryn C. B. Tan
  • Ching-Lung Cheung
  • Alan C. H. Lee
  • Joanne K. Y. Lam
  • Ying Wong
  • Sammy W. M. Shiu
Article

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 

Abbreviations

ACR

Albumin:creatinine ratio

ACEI

ACE inhibitor

ARB

Angiotensin II receptor blocker

CKD

Chronic kidney disease

Notes

Acknowledgements

Some of the data in this article were presented as an abstract at the 53rd EASD Annual Meeting in 2017.

Contribution statement

KCBT designed and oversaw the study, data collection, analysis and drafted the manuscript. CLC contributed to study design and analysed the data. SWMS performed the laboratory assays and analysed the data. YW, JKYL and ACHL recruited the participants and collected clinical data. All authors critically reviewed and approved the final version of the manuscript. KCBT is the guarantor of this work.

Funding

This study is supported by an Endowment Fund established for the ‘Sir David Todd Professorship in Medicine’, awarded to KCBT.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Supplementary material

125_2018_4552_MOESM1_ESM.pdf (143 kb)
ESM Figures (PDF 143 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Kathryn C. B. Tan
    • 1
  • Ching-Lung Cheung
    • 2
  • Alan C. H. Lee
    • 1
  • Joanne K. Y. Lam
    • 1
  • Ying Wong
    • 1
  • Sammy W. M. Shiu
    • 1
  1. 1.Department of MedicineUniversity of Hong Kong, Queen Mary HospitalHong Kong Special Administrative RegionPeople’s Republic of China
  2. 2.Department of Pharmacology and PharmacyUniversity of Hong KongHong Kong Special Administrative RegionPeople’s Republic of China

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