Indoxyl Sulfate Administration during Pregnancy Contributes to Renal Injury and Increased Blood–Brain Barrier Permeability

Abstract

Rates of pregnancy-related acute kidney injury (PR-AKI) have increased in the U.S over the past two decades, but how PR-AKI affects the blood–brain barrier (BBB) is understudied. AKI is associated with increased amounts of uremic toxins, like indoxyl sulfate (I.S), whose chronic administration leads to BBB and cognitive changes. This study’s objective was to determine if (1) PR-AKI increases I.S and (2) if administration of I.S during pregnancy elicits renal injury and/or increases BBB permeability. From gestational day (GD) 11 to GD19, Sprague Dawley rats were given either 100 or 200 mg/kg body-weight dose of I.S. PR-AKI was induced on GD18 via 45 min bilateral renal ischemic reperfusion surgery. On GD18, metabolic cage metrics and metabolic waste was collected and on GD19 blood pressure, and BBB permeability (by Evan’s Blue infusion) were measured. I.S and creatinine were measured in both urine and circulation, respectively. One-way ANOVA or student t-tests were performed using GraphPad Prism with a p < 0.05 significance. I.S and PR-AKI led to oliguria. I.S administration led to increased BBB permeability compared to normal pregnant and PR-AKI animals. These results suggest that I.S administration during pregnancy leads to increased BBB permeability and evidence of renal injury comparable to PR-AKI animals.

Special Issue of Pathogenesis of Pregnancy-Related Complications, 2023

“…Griffin et al [ 9 ] detail their research, in which administration of indoxyl sulphate (I.S), a uremic toxin, in a Sprague Dawley rat during pregnancy elicited renal injury comparable to pregnancy-related acute kidney injury (PR-AKI), which is induced in animals by bilateral renal ischemic reperfusion surgery. They also demonstrated that administration of I.S led to an increased blood–brain barrier permeability.…”