Kidney Injury Following Pregnancy Related (PR)-AKI

Background: Acute kidney injury during pregnancy (PR-AKI) is an obstetric complication that is associated with an increased risk of developing chronic kidney disease. Chronic kidney disease independent of pregnancy can lead to increased blood-brain barrier permeability and cognitive decline through an increase in inflammation, oxidative stress, and uremic toxins. Methods: Pregnant Sprague Dawley rats at gestational day (GD) 18 underwent a bilateral renal ischemia-reperfusion procedure for 45- min to induce renal injury. A subset of rats were treated with an oral carbon absorbent, AST-120, which absorbs the precursor of indoxyl sulfate in the gut. Normal pregnant (NP) rats served as a control, n=8/group. All rats were allowed to deliver at GD21-22 without interference. Renal function was assessed in the postpartum month four (PPM4). Creatinine and protein levels and urine output was assessed from the urine collected via the metabolic cages. Commercially available assays were used. Statistical tests (t-tests or one-way ANOVA where p<0.05) was used. Results: Urine output was decreased in PR-AKI rats from pregnancy throughout PPM4 vs. NP rats (p=0.02). Whereas proteinuria was significantly increased (p=0.005) in PR-AKI rats vs. NP rats. Despite the evidence for renal injury rats did not become hypertensive throughout the study (p=0.09). PR-AKI rats treated with AST had significant improvements in urine output (p=0.005), decreased proteinuria (p=0.006) and decreased renal fibrosis (p=0.05). Finally, both serum and urinary creatinine were significantly decreased in response to AST-120 treatment (p=0.02, 0.03). Conclusion: AKI during pregnancy leads to a renal injury phenotype. Postpartum AST-120 treatment slowed the progression to CKD from PR-AKI. In order to identify a safe therapeutic that can be administered during pregnancy, more experiments are needed to determine the exact role of indoxyl sulfate in the renal injury progression. We are currently examining the role of I.S. during pregnancy and the postpartum period. Funding: Private Foundation Support