Kidney Week

Abstract: SA-PO516

L-Homoarginine Supplementation Prevents Diabetic Kidney Damage

Session Information

• Diabetic Kidney Disease: Basic - III
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 601 Diabetic Kidney Disease: Basic

Authors

• Wetzel, Michael, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Michael Wetzel,

• Gao, Ting, Penn State College of Medicine, Hershey, Pennsylvania, United States

Ting Gao,

• Venkatachalam, Manjeri A., University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Manjeri A. Venkatachalam,

• Morris, Sidney M., University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Sidney M. Morris,

• Awad, Alaa S., University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Alaa S. Awad,

Background

Diabetes is the major cause of end stage renal disease, with heavy burden for the health care system. L-homoarginine (HA) is an endogenous, non-proteinogenic amino acid that is associated with renal and cardiovascular disease. Specifically, low HA levels are associated with cardiovascular diseases, stroke and reduced kidney function. However, the role of HA in diabetic nephropathy is unknown.

Methods

Six-week-old diabetic DBA Ins2^Akita and their controls were treated with or without HA supplementation via drinking water or mini osmotic pump for twelve weeks.

Results

Plasma and kidney HA levels were significantly reduced by 25% (p<0.05) and 65% (p<0.05) in Ins2^Akita; respectively compared to control mice. Vehicle-treated Ins2^Akita mice showed significant increases in urine albumin excretion (UAER) (p<0.01), renal histological changes (score: 1.5 vs. 0.25), glomerular macrophage recruitment (p<0.01), inflammatory KC-GRO/CXCL1 (p<0.0005), and urinary TBARS (p<0.0001); a marker of oxidative stress, along with reduction in kidney nitrate and nitrite levels (p<0.01) compared to non-diabetic controls. HA supplementation by either drinking water or osmotic pumps for 12 weeks in Ins2^Akita mice significantly reduced UAER (p<0.05), renal histological changes (score: 0.625 and 0.375), glomerular macrophage recruitment (p<0.05), KC-GRO/CXCL1 (p<0.005), and urinary TBARS (p<0.05), along with significant increase in kidney nitrate and nitrite levels (p<0.05) compared to vehicle-treated Ins2^Akita mice.

Conclusion

These data demonstrate that L-homoarginine supplementation attenuates specific features of diabetic nephropathy in mice and could be a potential new therapeutic tool for treating diabetic patients.

Funding

• NIDDK Support