Kidney Week

Abstract: SA-PO0285

Recovered Maternal AKI Affects Offspring Brain Development

Session Information

• AKI: Mechanisms - Cell Signaling
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Harrell, Paris R., Reed College, Portland, Oregon, United States

Paris R. Harrell

• Munhall, Adam C., Oregon Health & Science University, Portland, Oregon, United States

Adam C. Munhall

• Nickerson, Megan, Stanford University, Stanford, California, United States

Megan Nickerson

• Hutchens, Michael, Oregon Health & Science University, Portland, Oregon, United States

Michael Hutchens, MD, MA

• Hebert, Jessica Faith, Oregon Health & Science University, Portland, Oregon, United States

Jessica Faith Hebert, PhD

Background

Prior maternal acute kidney injury (AKI) diagnosis correlates with later pregnancy complications, resulting in offspring with later renal and cardiovascular dysfunction. Higher rates of hydrocephaly have been observed in young offspring. We hypothesized that recovered parental AKI results in impaired cerebrovascular development with the adult offspring brain more susceptible to inflammation, hemorrhage, and hydrocephalus.

Methods

8-week-old male and female mice were given adductor muscular glycerol injections (8mg/kg) to induce rhabdomyolysis-induced acute kidney injury (RIAKI; made by muscular glycerol injection) or sham treatment. After 2 weeks of recovery, they were bred like-to-like and offspring brains were collected at 12 weeks old. Brains were fixed, paraffin embedded, and sectioned coronally from Bregma +1 to -2. Relative ventricle size was measured using H&E-stained slides. Immunohistochemical staining for CD31 and GFAP was used to quantify astrocytes and cerebral vessels in sham and RIAKI-offspring brains. Statistical assessment was conducted by ANOVA (alpha 0.05) following Z-score tests.

Results

Pups born to RIAKI pairs were 3 times more likely to die in the perinatal period than those from shams. 3 pups (2 female, 1 male) developed hydrocephaly between 3 and 10 weeks of age. At 3 months old, when normalized to 3^rd ventricle for position normalization, lateral ventricles in brains from surviving female adult offspring of RIAKI parents were significantly larger than those from shams (p=0.01); males had no difference (p=0.13). No difference was observed in normalized dorsal third ventricle size. CD31 staining in the same region showed noticeably less expression in females from RIAKI parents than shams; males again were not different. No change was observed in GFAP signal in the brains.

Conclusion

This is the first study to report a difference in the brains of adult offspring following a historical parental renal insult. Larger lateral ventricles in adult offspring brains indicate a potential obstruction (possibly a clot or hemorrhage, based on loss of endothelial staining) increasing their size and raising the risk for hydrocephalus or developmental abnormalities, particularly in females who appear to have more significantly affected ventricular size. The mechanistic cause underlying abnormal brain development is currently under investigation in our lab.

Acknowledgment

We thank Dr. Helen Liu (OHSU APOM) for preparing the brain slides and H&E stains and the OHSU Advanced Light Microscopy Core for slide scans.

Funding

• NIDDK Support