Netrin-1, a urinary proximal tubular injury marker, is elevated early in the time course of human diabetes

J Nephrol. 2014 Apr;27(2):151-7. doi: 10.1007/s40620-014-0055-2. Epub 2014 Feb 8.


Background: Netrin-1 was recently identified as an early diagnostic biomarker of chronic kidney disease (CKD) in an experimental animal model. However, its usefulness for early diagnosis of CKD in humans is unknown. The current study evaluated whether netrin-1 is increased in urine from human diabetic patients.

Methods: Spot urine samples from healthy volunteers, diabetes without microalbuminuria, diabetes with microalbuminuria and diabetes with macroalbuminuria were collected after receiving consent. Netrin-1 in urine was quantified by enzyme-linked immunosorbent assay and the data analyzed to determine whether urinary netrin-1 significantly correlates with disease progression.

Results: Urinary netrin-1 levels were significantly increased in normoalbuminuric diabetic patients compared to healthy controls, and still further elevated in patients with microalbuminuria and overt nephropathy. Urinary netrin-1 was significantly associated with albuminuria and estimated glomerular filtration rate, independently of age and sex.

Conclusion: Netrin-1 is detectable in urine from diabetic patients and may serve as a useful early diagnostic biomarker predicting the development of CKD in diabetes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Albuminuria / complications
  • Albuminuria / urine
  • Biomarkers / urine
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / diagnosis*
  • Diabetic Nephropathies / urine*
  • Disease Progression
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney Tubules, Proximal / pathology
  • Male
  • Middle Aged
  • Nerve Growth Factors / urine*
  • Netrin-1
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / physiopathology
  • Renal Insufficiency, Chronic / urine*
  • Time Factors
  • Tumor Suppressor Proteins / urine*


  • Biomarkers
  • NTN1 protein, human
  • Nerve Growth Factors
  • Tumor Suppressor Proteins
  • Netrin-1