Pregnancy-related acute kidney injury leads to hypertension, reduced kidney function and cognitive impairment in postpartum rats

Ashley Griffin; Jamie Szczepanski; Shauna-Kay Spencer; Lucia Solis; Teylor Bowles; Reanna Robinson; Jan M Williams; Patrick B Kyle; Kedra Wallace

doi:10.3389/fphys.2024.1468793

Pregnancy-related acute kidney injury leads to hypertension, reduced kidney function and cognitive impairment in postpartum rats

Front Physiol. 2024 Nov 25:15:1468793. doi: 10.3389/fphys.2024.1468793. eCollection 2024.

Authors

Ashley Griffin^#¹, Jamie Szczepanski^#², Shauna-Kay Spencer^{2

3}, Lucia Solis², Teylor Bowles², Reanna Robinson², Jan M Williams³, Patrick B Kyle⁴, Kedra Wallace^{2

3}

Affiliations

¹ Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, United States.
² Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS, United States.
³ Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, United States.
⁴ Department of Pathology, University of Mississippi Medical Center, Jackson, MS, United States.

^# Contributed equally.

Abstract

Introduction: Women with hypertensive disorders of pregnancy such as HELLP (hemolysis, elevated liver enzyme, low platelet) Syndrome are affected by acute kidney injury during pregnancy (PR-AKI) at higher rates than women without hypertension. Both hypertensive disorders of pregnancy and Acute Kidney Injury (AKI) outside the context of pregnancy have been associated with an increased risk of developing Chronic Kidney Disease (CKD) and cognitive impairment. In our current study, we set out to determine if PR-AKI led to the development of CKD and impaired cognition in the postpartum period and if HELLP syndrome exacerbates the impairments.

Methods: Using timed-pregnant Sprague Dawley rats, on gestational day (GD) 12, mini-osmotic pumps infusing anti-angiogenic factors were surgically placed in the intraperitoneal cavity to induce HELLP. On GD18, AKI was induced via bilateral renal reperfusion ischemia surgery. Mean arterial pressure and birth outcomes were used to assess the global effects of AKI, and liver enzymes were used to assess HELLP. CKD was assessed by measuring glomerular filtration rate (GFR), urinary output, and renal fibrosis. Anxiety-like behaviors, object recognition memory, spatial memory, and avoidance memory were assessed via behavioral experiments.

Results: HELLP + AKI rats demonstrated more evidence of renal injury, hypertension, and behavioral deficits compared to normal pregnant animals. In addition, AKI had a negative impact on birth outcomes and maternal survival.

Conclusion: HELLP + AKI together led to evidence of persistent hypertension, progressive renal dysfunction, and cognitive impairment, which were exacerbated compared to AKI or HELLP alone. These findings suggest that PR-AKI in the presence of a hypertensive disorder of pregnancy, such as HELLP, leads to the development of CKD, cognitive dysfunction, and hypertension.

Keywords: AKI; CKD; HELLP syndrome; cognition; memory; postpartum; pregnancy; renal injury.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. Research reported in this publication was supported in part by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) under Award Number P20GM121334 and P20GM104357; by an Institutional Development Award (IDeA) from NIH/NIGMS under award Number P20GM103476; National Heart, Lung and Blood Institute of NIH under Award Number P01HL51971. Support was also from National Institute of Diabetes and Digestive and Kidney of NIH under Award Number DK109133 and National Institute of Aging of the National Institutes of Health (NIH/NIA, R01AG057842) to JMW and NIH to T32HL105324 to AG. Additional support was received from American Physiological Society William Townsend Porter Predoctoral Fellowship to AG and Chan Zuckerberg Initiative DAF grant number CZI 311112 to KW. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.