Tubular injury marker netrin-1 is elevated early in experimental diabetes

Background: Netrin-1 was recently identified as an early diagnostic biomarker of acute kidney injury. However, its usefulness for early diagnosis of chronic kidney disease (CKD) is unknown. The current study evaluated whether these proteins are increased in urine from experimental animals with diabetes. Methods: The current study evaluated whether netrin-1 is increased in urine from diabetic rats and mice, and whether netrin-1 correlated with development of nephropathy. Results: In rats, urinary netrin-1 excretion was significantly (p<0.001) higher in the diabetic group at 4 and 10 weeks after induction of diabetes as compared with the control group. Similarly, netrin-1 was increased significantly (p<0.001) in urine from hypertensive rats at 4 weeks as compared with controls. Likewise, urinary albumin excretion rates were increased in diabetic rats at 4 and 10 weeks as compared with controls and were increased in hypertensive rats at 4 weeks. Consistent with the diabetic model in rats, netrin-1 excretion was also increased early in diabetic mice's urine, and peak levels correlated with disease severity. Conclusion: Netrin-1 can be detected in urine from diabetic and hypertensive rats and may serve as a useful early diagnostic biomarker for development of CKD.