Acute kidney injury during pregnancy leads to increased sFlt-1 and sEng and decreased renal T regulatory cells in pregnant rats with HELLP syndrome

• Published in: Biology of sex differences 2020-09, Vol.11 (1), p.54-10, Article 54
• Main Authors: Szczepanski, Jamie, Spencer, Shauna-Kay, Griffin, Ashley, Bowles, Teylor, Williams, Jan Michael, Kyle, Patrick B, Dumas, John Polk, Araji, Sarah, Wallace, Kedra
• Format: Article
• Language: English
• Subjects: Abdomen; Angiogenesis; Animals; Animals, Newborn; Aspartate; Aspartate aminotransferase; Bioassays; Biochemical markers; Biomarkers - blood; Biomarkers - urine; Birth Weight; Blood Pressure; Catheters; CD3 antigen; CD4 antigen; Creatinine; Endoglin; Endoglin - genetics; Endoglin - metabolism; Enzymes; Female; Fibrosis; Gelatinase; Glomerular filtration rate; Health aspects; HELLP Syndrome; Hypertension; Immunoregulation; Ischemia; Kidney - cytology; Kidney Diseases - etiology; Kidney Diseases - pathology; Kidneys; L-Lactate dehydrogenase; Lactic acid; Lipocalin; Liver; Lymphocytes T; Platelets; Postpartum period; Pre-eclampsia; Preeclampsia; Pregnancy; Protein-tyrosine kinase; Rats; Rats, Sprague-Dawley; Reperfusion; Rodents; Software; Surgery; T cells; T-Lymphocytes, Regulatory; Tyrosine; Urine; Vascular Endothelial Growth Factor Receptor-1 - genetics; Vascular Endothelial Growth Factor Receptor-1 - metabolism; Womens health
• ISSN: 2042-6410; 2042-6410
• DOI: 10.1186/s13293-020-00331-6

The incidence of acute kidney injury (AKI) during pregnancy precedes a high maternal mortality rate of 20-40%. AKI during pregnancy has multiple etiologies; however, the more common are maternal hypertensive disorders, which include preeclampsia and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome. Therefore, we sought to assess the impact of AKI on blood pressure, kidney injury, and anti-angiogenic factors during pregnancies with and without HELLP syndrome. On gestational day (GD) 12, mini-osmotic pumps were inserted into a subset of normal pregnant (NP) rats infusing 4.7 μg/kg soluble fms-like tyrosine kinase-1 (sFlt-1) and 7 μg/kg soluble endoglin (sEng) to induce HELLP syndrome. On GD18, the renal pedicles were occluded for 45 min to induce AKI via bilateral ischemia reperfusion in a subset of NP (n = 18) or HELLP (n = 20) rats. Control NP (n = 20) and HELLP (n = 20) rats underwent a SHAM surgery on GD18. Plasma, urine, and maternal organs were saved for further analysis. Renal injury was assessed via renal histopathology, glomerular filtration rate (GFR), T cell infiltration, and assessment of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Data was measured via two-way analysis of variance with Tukey's test for post hoc analysis. Blood pressures were increased in HELLP+AKI rats (p = 0.0001); both NP+AKI and HELLP+AKI rats had increased lactate dehydrogenase (p < 0.0001) and aspartate aminotransferase levels (p < 0.0001), and decreased platelet levels (p < 0.001) vs. NP rats. HELLP+AKI (p = 0.002) and HELLP rats (p = 0.0002) had evidence of renal fibrosis vs. NP rats. GFR was decreased in HELLP+AKI (p = 0.01) rats vs. NP rats. Urinary KIM-1 was increased in NP+AKI rats vs. NP (p = 0.003) and HELLP rats (p = 0.01). HELLP+AKI rats had increased urinary KIM-1 vs. NP (p = 0.0008) and HELLP rats (p = 0.004) and increased NGAL vs. HELLP rats (p = 0.002). HELLP+AKI rats had increased sFlt-1 (p = 0.009) vs. NP rats. NP+AKI (p = 0.02) and HELLP+AKI (p = 0.007) rats had increased sEng vs. NP rats. CD3 CD4 T cells were significantly increased in HELLP+AKI rats vs. NP (p = 0.0002) and NP+AKI (p = 0.05) rats. T regulatory cells were significantly decreased in HELLP+AKI (p = 0.03) and NP+AKI (p = 0.02) rats vs. NP rats; there were no changes between groups in T helper 17 cells (p = 0.34). The findings in this study suggest that AKI during pregnancy contributes to increased blood pressure and biochemical markers