Blood Brain Barrier is functional 24 hours following Pregnancy related Acute Kidney Renal Injury
Authors: Griffin Ashley , Szczepanski Jamie Lynn , Berry Brittany , Spencer Shauna-Kay , Smith Stanley , Frieson Danielle , Williams Jan , Wallace Kedra 
Published: May 2023

From 1999 to 2011, incidences of pregnancy related acute kidney injury (PR-AKI) increased from 2.4 to 6.3 per every 10,0000 deliveries in the U.S. Acute Kidney Injury (AKI) is associated with increased circulating uremic toxins such as indoxyl sulfate (I.S) and p cresyl sulfate (PCS), cognitive dysfunction and blood brain barrier (BBB) disruption. The purpose of these experiments was to determine if 24 hours following AKI there is evidence of BBB dysfunction in a model of PR-AKI. We hypothesized that AKI would lead to BBB disruption while the treatment of I.S alone does not as our overall hypothesis is that accumulation of uremic toxins following renal injury leads to cognitive dysfunction. Time-pregnant Sprague Dawley rats arrived on gestational day (GD)10 and were randomized into the following groups: normal pregnant (NP; n=5-9), AKI (n=5-8), 100 I.S (n=5-10), and 200 I.S (n=5-9). Beginning on GD11, a subset of rats received either 100 mg/kg body weight (BW) or 200 mg/kg BW dose of I.S via drinking water daily. On GD18, AKI rats received a 45-min bilateral renal ischemic reperfusion surgery. On GD19, blood pressure was taken via CODA tail cuff followed by organ and blood collection. Five animals per group were injected with 4% Evan’s Blue (EB) for 30 mins and flushed with saline. Residual EB was measured in the frontal and posterior cortices, brain stem, and cerebellum. Serum was used to measure I.S and PCS via mass spectrometry. Creatinine was measured in both urine and serum via assay (BioAssay Systems). Data was analyzed via one-way ANOVA followed by multiple comparisons via GraphPad Prism. Statistical significance was determined as p<0.05. AKI animals had a higher kidney weight/BW ratio to NP (p=0.04), 100 I.S (p=0.003), and 200 I.S (p=0.04) while 200 I.S had a larger kidney to BW ratio to NP rats (p=0.02). AKI had smaller spleen weight/BW(p=0.02) ratios compared to NP rats. Pups born to AKI dams were significantly smaller than NP (p=0.001), 100 I.S (p=0.01), and 200 I.S (p <0.0001) dams. 200 I.S (p=0.02) had an increase in placental efficiency (placenta weight/ pup weight) compared to NP rats. Circulating I.S is significantly decreased in 100 I.S rats compared to NP (p=0.04) and AKI (p=0.04). PCS was significantly increased in AKI rats compared to NP (p=0.02), 100 I.S (p=0.03), and 200 I.S (p=0.03). When EB was measured, 200 I.S had significantly more EB in the brain stem region (p=0.01) compared to AKI rats. A one-way ANOVA showed differences in creatinine levels between groups (p=0.04), but multiple comparisons showed no differences between specific groups. PR-AKI led to changes in kidney and spleen weight without differences in BW which could be contributed by the immune response of the injury. We have preliminary data showing increases in circulating I.S 4 months post-partum which suggests increases occur later in postpartum. The brain stem is an interest of study as it has been shown to be implicated in chronic renal failure.

Funding to AG (William Townsend Porter Predoctoral Fellowship from American Physiological Society), to KW (Chan Zuckerberg Initiative Science Diversity Leadership Award)

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.