Abstract: FR-PO184
Low Birthweight Impacts the Ability to Recover from Childhood AKI in Mice
Session Information
- AKI: Mechanisms
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Timberline, Sage, University of Virginia, Charlottesville, Virginia, United States
- Deronde, Kimberly, University of Virginia, Charlottesville, Virginia, United States
- Johnson, Wyatt, University of Virginia, Charlottesville, Virginia, United States
- Bennett, Kevin M., Washington University in St Louis, St Louis, Missouri, United States
- Charlton, Jennifer R., University of Virginia, Charlottesville, Virginia, United States
Background
Low birthweight is a risk factor for the development of chronic kidney disease (CKD). Birth weight and nephron number are highly correlated. In rodents, maternal protein restriction during gestation results in low birthweight offspring with fewer nephrons. Acute kidney injury (AKI) independently increases the risk of CKD. However, the impact of low birthweight on the ability to recover from AKI is unknown.
Methods
Pregnant CD-1 dams were fed a normal protein (NP, 18%) or low protein (LP, 8%) diet from conception through weaning. NP and LP offspring were stratified to receive vancomycin (400 mg/kg intraperitoneal on days 7 and 8, n=6-12/group) or no injection, creating four groups – NPV, LPV, NP0, LP0. At 6 weeks, glomerular filtration rate (GFR) was measured transcutaneously. Kidneys were prepared for histologic evaluation of atubular glomeruli percentage (ATG) using Amira (Thermo Fisher Scientific software). Data were analyzed using Prism 9 (GraphPad software) with significance set at p<0.05. Groups were stratified by sex a priori.
Results
LP0 males had lower GFRs and more ATG compared to NP0 males (Table). After AKI, all LPV animals had lower GFRs and more ATG compared to same-sex NPV animals. When compared to LP0, LPV animals had more ATG. LPV animals had lower GFRs than NPV animals. LPV males had lower GFRs compared to LP0 males, while LPV and LP0 females were similar.
Conclusion
Changes in kidney structure and function after AKI were more severe in LP animals. LP animals exposed to vancomycin AKI had more ATGs, suggesting that AKI is an additional risk factor for development of non-functional glomeruli in low birthweight animals. LP animals exposed to vancomycin AKI also had lower GFRs compared to NPV animals, but only LPV males had lower GFRs than LP0 counterparts. This suggests that the degree of impact on kidney function from AKI on low birthweight animals may be sex-specific.
Outcomes for Diet/AKI/Sex Groups
| Diet/Sex/AKI groups | NP-V | LP-0 | LP-V | NP-V vs. LP-V | LP-0 vs LP-V | |||||
| Sex | M | F | M | F | M | F | M | F | M | F |
| Outcomes | Median (IQR) | P value | ||||||||
| Body weight (grams) | 35 (29-37) | 28 (27-31) | 29 (28-31) | 23 (21-24) | 24 (22-30) | 21 (20-24) | *** | *** | ** | -- |
| Kidney weight/body weight (%) | 1.3 (1.2-1.4) | 0.9 (0.8-1.0) | 1.7 (1.6-1.9) | 1.4 (1.3-1.5) | 1.1 (1.0-1.4) | 0.9 (0.8-1.1) | -- | -- | ** | *** |
| GFR (uL/min) | 311 (221-351) | 297 (202-394) | 201 (195-254) | 198 (188-271) | 154 (32-171) | 170 (77-243) | *** | ** | * | -- |
| Atubular glomeruli (%) | 54 (37-65) | 55 (49-63) | 32 (31-36) | 54 (49-59) | 76 (69-79) | 82 (74-85) | ** | *** | *** | *** |
NP: normal protein. LP: low protein. V: vancomycin. 0: no injection. M: male. F: female. ***: p<0.001. **: p<0.01. *: p<0.05. --: p>0.05.
Funding
- NIDDK Support