Kidney Week

Abstract: SA-PO129

Low Doses of GDT-01 Improve Diabetic Nephropathy and Preserve GFR in ZSF1 Rats over 7 Months by Improving In Vivo Sialylation

Session Information

• Diabetic Kidney Disease: Basic - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Chugh, Sumant S., Rush University Medical Center, Chicago, Illinois, United States

Sumant S. Chugh,

• Kharlyngdoh, Joubert Banjop, Rush University Medical Center, Chicago, Illinois, United States

Joubert Banjop Kharlyngdoh,

• Del Nogal Avila, Maria, Rush University Medical Center, Chicago, Illinois, United States

Maria Del Nogal Avila,

• Das, Ranjan, Rush University Medical Center, Chicago, Illinois, United States

Ranjan Das,

• Donoro blazquez, Hector, Rush University Medical Center, Chicago, Illinois, United States

Hector Donoro blazquez,

• Molina-Jijon, Eduardo, Rush University Medical Center, Chicago, Illinois, United States

Eduardo Molina-Jijon,

• Clement, Lionel C., Rush University Medical Center, Chicago, Illinois, United States

Lionel C. Clement,

• Mace, Camille E., Rush University Medical Center, Chicago, Illinois, United States

Camille E. Mace,

• Avila-Casado, Carmen, University Health Network, University of Toronto, Toronto, Ontario, Canada

Carmen Avila-Casado,

Group or Team Name

• Glomerular Disease Therapeutics Laboratory

Background

Studies on rat diabetic nephropathy using the previously published sialic acid precursor ManNAc (Clement LC et al Nature Medicine Jan 2011) worsen hyperglycaemia in ZDF rats, which is harmful in the long term. We conducted a 7 month study to improve in vivo sialylation in the glomerulus using the compound GDT-01 with the goal of studying its effect on CKD and hyperglycaemia in rat diabetic nephropathy.

Methods

We treated 5 month old male ZSF1 rats (n = 6 rats / group) with taps water or GDT-01 in tap water over a period of 7 months, and measured proteinuria, BUN, creatinine, blood glucose, other blood parameters, and assessed renal histological changes on the termination of the study.

Results

A declining dose regimen for GDT-01 was used, and the actual dose delivered (mg / Kg; mean + SE) over 3 separate periods was as follows: Period A, Days 0 to 95, 136.8 + 11.8; Period B, Days 96 to 122, 21.5 + 5; Period 3, Days 123 to 222, 3.7 + 0.2. Proteinuria was consistently lower in the treated group in Period C (10/14 readings, P<0.05), occasionally in Period B (1/4 readings) and rarely lower in Period A (2/14 readings). Blood glucose levels were similar between the GDT-01 and water groups. BUN and creatinine were consistently lower in the treatment group in Period C (BUN, 7/14, P < 0.05 to 0.01; creatinine, 5/14, P<0.05), and only occasionally in Periods A and B. Detailed renal histology and sialylation analysis are ongoing.

Conclusion

Low oral doses of the sialylation inducing compound GDT-01 improve GFR and proteinuria over prolonged periods of time without worsening hyperglycaemia in ZSF1 diabetic rats.

Funding

• NIDDK Support