Abstract: SA-PO732
Effects of AMPK Deficiency and Sex-Differences in Kidney Parameters Post Uninephrectomy
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Pastor-Soler, Nuria M., Keck School of Medicine of USC, Garden grove, California, United States
- Hallows, Kenneth R., Keck School of Medicine of USC, Garden grove, California, United States
- Pham, Jessica, Keck School of Medicine of USC, Garden grove, California, United States
- Rivera, Daniel, Keck School of Medicine of USC, Garden grove, California, United States
- Saitta, Biagio, Keck School of Medicine of USC, Garden grove, California, United States
Background
Living donor (LD) kidney transplant is the preferred therapy for end-stage kidney disease. LDs have generally excellent outcomes, yet some show that in the first year post-UNX there is an increased risk of hypertension and microalbuminuria. It is unclear whether compensatory kidney changes are beneficial to the LD long term. In some chronic kidney disease (CKD) models activity of the metabolic sensor AMP-activated kinase (AMPK) is lower compared to healthy kidneys. We hypothesized that low AMPK activity pre-UNX could worsen CKD post-UNX when combined with a high-Na+ diet in both male and female mice. Our work aims to inform mechanisms that could lead to protective interventions for LDs with AMPK activation.
Methods
We used adult male and female mice with double-floxed AMPK alpha subunit (AMPKfl) and ± tamoxifen-driven (tam) expression of Cag-Cre recombinase (Cre+ vs. Cre-AMPKfl). Mice underwent UNX 5 wks post-Tam (vs. Sham surgery) and were all placed on a high-Na+ (HNa) diet at that time (intervention). We measured GFR, urine albumin and plasma electrolytes at different time points. Kidneys were examined by immunoblot and qPCR.
Results
Cre+AMPKfl males and females kidneys had significant AMPK knockdown (KD) compared to Cre-AMPKfl mice after tam. Females.AMPK-KD (Cre+ mice) females had a significant increase in albuminuria compared to AMPK-sufficient mice, although we did not detect such change in males. AMPK-KD mice had significantly worse anemia compared to AMPK-sufficient mice in both males and females.
Although we found that GFR increased after UNX+HNa in AMPK-sufficient females, this compensatory hyperfiltration was not evident in the AMPK-D female mice. In male mice that were AMPK-sufficient we did not observe compensatory hyperfiltration post UNX+HNA (as estimated by blood urea nitrogen (BUN). In contrast, in AMPK-D mice, UNX+HNa had a detrimental effect on BUN.
Conclusion
AMPK KD in both male and female mice worsens kidney injury in a model of kidney donation and HNa diet. These findings implicate AMPK as an important target for potential pharmacological interventions to prevent CKD in men and women LDs.
Funding
- Private Foundation Support