Kidney Week

Abstract: SA-PO731

Marmoset - A Non-Human Primate Model to Study Aging Associated Changes in the Kidney

Session Information

• Geriatric Nephrology
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Geriatric Nephrology

• 1100 Geriatric Nephrology

Authors

• Lee, Hak Joo, University of Texas Health Science Center, San Antonio, Texas, United States

Hak Joo Lee,

• Gonzalez, Olga D., Texas Biomed, San Antonio, Texas, United States

Olga D. Gonzalez,

• Dick, Edward J., Texas Biomedical Research Institute, San Antonio, Texas, United States

Edward J. Dick,

• Donati, Andrew, University of Texas Health Science Center, San Antonio, Texas, United States

Andrew Donati,

• Feliers, Denis, University of Texas Health Science Center, San Antonio, Texas, United States

Denis Feliers,

• Ghosh-Choudhury, Goutam, University of Texas Health Science Center, San Antonio, Texas, United States

Goutam Ghosh-Choudhury,

• Ross, Corinna, Texas A&M San Antonio, San Antonio, Texas, United States

Corinna Ross,

• Venkatachalam, Manjeri A., University of Texas Health San Antonio, Shavano Park, Texas, United States

Manjeri A. Venkatachalam,

• Tardif, Suzette D., Texas Biomedical Research Institute, San Antonio, Texas, United States

Suzette D. Tardif,

• Kasinath, Balakuntalam S., University of Texas Health Science Center, San Antonio, Texas, United States

Balakuntalam S. Kasinath,

Background

Because of the genetic distance between rodents and humans an appropriate primate model to study kidney aging is needed. We evaluated whether the marmoset can fill this need by studying kidney parameters in healthy young and aged marmosets of both sexes.

Methods

We studied 4 young male (average age 3 years) and 4 young female (average age 2.8 years) marmosets, and, 5 aged male (average age 16.1 years) and 5 aged female (average age 15.9 years) marmosets. We examined structural changes in the kidney by H and E and PAS stains. Immunoblotting was employed to study changes in the expression of proteins. Measurement of urinary albumin and protein was by ELISA and Bio-Rad assay, respectively.

Results

Aging was associated with glomerulosclerosis, tubulointerstitial fibrosis and arteriolosclerosis constituting nephrosclerosis in both sexes; patchy areas of interstitial nephritis were seen. The renal cortical content of matrix proteins laminin, type III collagen, and fibronectin was increased on immunoblotting. Functionally, aging resulted in an increase in urinary albumin to creatinine ratio and protein to creatinine ratio in association with reduction in kidney expression of nephrin. There was a robust correlation between histologic markers of fibrosis and albuminuria and proteinuria. We explored signaling pathways as potential mechanistic events. Aging in males, but not in females, was associated with reduced renal cortical activity of AMP-activated protein kinase (AMPK) and a trend toward activation of mechanistic target of rapamycin complex 1 (mTORC1); upstream of AMPK and mTORC1, Akt and insulin–like growth factor 1 receptor were activated. In both sexes, aging promoted renal cortical expression transforming growth factor β-1 and phospho-Smad3. Since kidney fibrosis is associated with deficiency of hydrogen sulfide synthesis in renal disease, we examined its status in aging marmosets. While the expression of cysthathionine β-synthase, an enzyme involved H₂S synthesis, was reduced in both aged males and females, decreased H₂S generation was seen only in the males.

Conclusion

Our studies show that the marmoset is a valid model to study kidney aging; some of the signaling pathways involved in renal senescence differ between male and female marmosets.

Funding

• Veterans Affairs Support