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Abstract: PO1813

Urinary Glycogen Synthase Kinase 3β Level Predicts the Progression of Hypertensive Nephrosclerosis

Session Information

Category: Hypertension and CVD

  • 1402 Hypertension and CVD: Clinical, Outcomes, and Trials

Authors

  • Zeng, Lingfeng, Department of Medicine & Therapeutics and Li Ka Shing Institute of Health Sciences (LiHS), Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China, Hong Kong
  • Szeto, Cheuk-Chun, Department of Medicine & Therapeutics and Li Ka Shing Institute of Health Sciences (LiHS), Faculty of Medicine, The Chinese University of Hong Kong, Shatin, China, Hong Kong
Background

Hypertensive nephrosclerosis (HTN) is a serious consequence of prolonged hypertension. In the United States, HTN is the second most common cause of end-stage kidney disease. Recently, emerging evidence suggests that glycogen synthase kinase (GSK) 3β is a key factor in the progression of diabetic kidney disease (DKD). However, it remains uncertain whether the role of GSK3β is specific for DKD or a generic mediator of renal damage irrespective to the underlying cause.

Methods

We studied 32 patients with biopsy-proved HTN patients. Their GSK3β level in urinary supernatant was measured by conventional ELISA, and GSK3β mRNA level in urinary sediment was measured by quantitative polymerase chain reaction. The results were compared to the baseline kidney function and the subsequent risk of renal function deterioration.

Results

The average urinary GSK3β level was 212.67 ± 47.74 ng/L by conventional ELISA, which closely correlated with its mRNA level in urinary sediment (r = 0.821, P<0.0001). Urinary GSK3β level significantly correlated with baseline glomerular filtration rate (GFR) (r=-0.451, p=0.010) and the slope of GFR decline (r=-0.397, p=0.033). Patients with a high urinary GSK3β level has a higher risk of developing 40% kidney function loss and progressing to dialysis-dependent kidney failure than those with a low GSK3β level (log rank test, p=0.028 and p=0.043, respectively). Similarly, urinary GSK3β mRNA level also significantly correlated with baseline GFR (r=-0.582, p<0.0001) and the slope of GFR decline (r=-0.402, p=0.022). Patients with a high urinary GSK3β mRNA level has a higher risk of developing 40% kidney function loss and progressing to dialysis-dependent kidney failure than those with a low GSK3β level (p=0.022 and p= 0.004, respectively).

Conclusion

These results demonstrated that urinary GSK3β level correlates with the rate of kidney function loss in patients with biopsy-proved HTN, and urinary sediment mRNA level appears to be a more accurate prognostic marker than urinary GSK3β level by ELISA. Our results suggest that GSK3β is a generic mediator for the progression of chronic kidney disease and is not specific for DKD.

Funding

  • Clinical Revenue Support