Abstract: FR-PO876
Recovered Parental AKI Results in Dysfunctional Pregnancy and Offspring Programming
Session Information
- Women's Health and Kidney Diseases
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Women's Health and Kidney Diseases
- 2200 Women's Health and Kidney Diseases
Authors
- Hebert, Jessica Faith, Oregon Health & Science University, Portland, Oregon, United States
- Emathinger, Jacqueline M., Oregon Health & Science University, Portland, Oregon, United States
- Andeen, Nicole K., Oregon Health & Science University, Portland, Oregon, United States
- Gurley, Susan B., Oregon Health & Science University, Portland, Oregon, United States
- Hutchens, Michael, Portland VA Medical Center, Portland, Oregon, United States
Background
Rhabdomolysis-induced acute kidney injury (RIAKI) follows muscular trauma and is observed in people of childbearing age. Although apparent recovery is common, prior AKI increases the risk of renal and reproductive disease. We hypothesized that recovered AKI induces pregnancy complications and developmentally programs offspring disease.
Methods
Procedures were approved by institutional IACUC. Rhabdomyolysis in 8-12 week old C57BL/6J mice was induced via intramuscular injection of 50% glycerol (8 mL/kg); shams were untreated. AKI was assessed 24 hours later via glomerular filtration rate (GFR; uL/min/100g body weight) and repeated 2 weeks post-recovery to establish functional recovery, followed by 1) timed sham/sham and RIAKI/RIAKI matings for pregnancy (gestational day (GD) 16.5) and 2) adult offspring (12 weeks, 6 months) effects. Urine was collected 24 hours before GFR and tissue harvest for later analysis. Statistics were assessed by t-test for 2 group analyses, and 2-way ANOVA with posthoc tests for analyses by sex.
Results
1) Despite normal GFR pre-pregnancy, recovered RIAKI dams had lower GFR than shams at GD 16.5 (p<0.01). Fetoplacental ratio was lower in RIAKI offspring (p<0.01) with no difference in litter size but 3x more perinatal death. Albuminuria (p<0.01) was observed in RIAKI dams. RIAKI dams had less megalin (p<0.05) and more angiotensin II (AngII) in the proximal tubule brush border than shams, with evidence of subcapsular fibrosis. 2) Offspring of recovered RIAKI parents have sexually dimorphic responses related to renal function. GFR was reduced in offspring of both sexes by 6 months (males: p<0.05, females: p<0.01). Circulating AngII levels were decreased in plasma from only female RIAKI offspring compared to shams (p<0.05); however, adult males from RIAKI pairings gained more weight than sham males between young and middle adulthood (p<0.05).
Conclusion
RIAKI poses reproductive risk long after initial apparent recovery, likely due to new proximal tubule dysfunction in the setting of pregnancy after RIAKI. Renal function in pregnancy, particularly essential function of the proximal tubule via megalin and AngII, is altered by prior RIAKI and developmentally programs offspring with adult-onset reduced GFR, and older male offspring with increased weight gain.
Funding
- Other NIH Support