(1793) Low Birthweight Impacts the Ability to Recover From Childhood Acute Kidney Injury in Mice

Introduction: Low birthweight is a risk factor for chronic kidney disease (CKD). Birthweight and nephron number are highly correlated. In rodents, maternal protein restriction during gestation results in low birthweight offspring with fewer nephrons, mimicking human traits. Acute kidney injury (AKI) independently increases CKD risk. However, the impact of low birthweight on ability to recover from AKI is unknown. Our goal is to determine whether low birthweight mice have more severe structural and functional changes after AKI using a maternal protein restriction model.

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 to induce AKI (400mg/kg intraperitoneal on day 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 fraction (ATG) using Amira (Thermo Fisher Scientific software). Data were analyzed by Student’s t-test using Prism 9 (GraphPad software) with significance set at p< 0.05. Groups were stratified by sex a priori.

Results: In absence of AKI, LP0 males had lower GFRs and more ATG compared to NP0 males; LP0 and NP0 females were similar. With AKI, all LPV animals had lower GFRs and more ATG compared to same-sex NPV animals. All LPV animals also had more ATG than LP0 animals; NPV and NP0 animals were similar. However, only LPV males had lower GFRs compared to LP0 males, while LPV and LP0 females were similar. AKI in all animals was associated with lower kidney weight/body weight ratio.

Conclusions: Changes in kidney structure and function after AKI were more severe in LP animals. LP animals exposed to AKI had more ATG than both LP0 and NPV animals, suggesting AKI is an additional risk factor for development of non-functional glomeruli in low birthweight animals. LP animals exposed to AKI also had lower GFRs compared to NPV animals, but only LPV males had lower GFRs than LP0 counterparts. Thus, degree of impact on kidney function from AKI on low birthweight animals may be sex-specific. Next steps will include RNA sequencing to better characterize molecular changes and identify potential therapies.