Postpartum Placental Ischemic Dams Display an Increase in Kidney Cortex TNF-α and Kidney Medulla Nitric Oxide Bioavailability with High Blood Pressure

Women who experience a placental ischemic (PI) pregnancy, such as preeclampsia, have an increased risk of developing chronic kidney disease (CKD) as early as 5-20 years postpartum. The underlying mechanisms leading to this increased risk for CKD are unknown. Mechanisms that contribute to the development of CKD are hypertension and changes in renal molecular factors such as inflammation, oxidative stress, and nitric oxide (NO) bioavailability. To determine the relationship between blood pressure, renal molecular factors, and CKD in women after a PI pregnancy, we used the reduced uterine perfusion pressure model of preeclampsia in rats. In this study, two groups were utilized: normal pregnant (NP) and PI dams. At 6 weeks postpartum (∼2-3 human years), we examined the dams’ blood pressure via carotid catheterization, collected the plasma to measure creatinine, and obtained the kidneys to evaluate the abundance and concentrations of renal molecular factors. PI dams exhibited an increase in blood pressure (125±3vs111±3 mmHg, p=0.002), TNF-α in the kidney cortex (81.38±1.1vs67.48±0.58 pg/mL / mg Protein, p<0.0001), and increased NO bioavailability (0.64±0.08vs0.41±0.05 µmol NO ₃ /mg Protein, p=0.03) in the kidney medulla. However, serum creatinine, renal KIM-1, eNOS, NGAL, and oxidative stress did not have significant changes. In summary, PI dams have alterations in kidney inflammation and NO bioavailability, with no indications of renal dysfunction or injury. Thus, suggesting that changes in renal molecular factors may precede the onset of CKD. This study is clinically relevant, because it highlights the potential contributions of altered renal molecular factors in development of CKD postpartum.