PMID- 32972452 OWN - NLM STAT- MEDLINE DCOM- 20210804 LR - 20240429 IS - 2042-6410 (Electronic) IS - 2042-6410 (Linking) VI - 11 IP - 1 DP - 2020 Sep 24 TI - Acute kidney injury during pregnancy leads to increased sFlt-1 and sEng and decreased renal T regulatory cells in pregnant rats with HELLP syndrome. PG - 54 LID - 10.1186/s13293-020-00331-6 [doi] LID - 54 AB - BACKGROUND: 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. METHODS: On gestational day (GD) 12, mini-osmotic pumps were inserted into a subset of normal pregnant (NP) rats infusing 4.7 mug/kg soluble fms-like tyrosine kinase-1 (sFlt-1) and 7 mug/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. RESULTS: 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). CONCLUSION: The findings in this study suggest that AKI during pregnancy contributes to increased blood pressure and biochemical markers for HELLP syndrome, creates an anti-angiogenic imbalance, and exacerbates kidney injury as shown on histopathology, GFR, and kidney injury markers. FAU - Szczepanski, Jamie AU - Szczepanski J AD - Department of Obstetrics & Gynecology, University of Mississippi Medical Center, 2500 North State St, Jackson, MS, 39216, USA. FAU - Spencer, Shauna-Kay AU - Spencer SK AD - Department of Obstetrics & Gynecology, University of Mississippi Medical Center, 2500 North State St, Jackson, MS, 39216, USA. FAU - Griffin, Ashley AU - Griffin A AD - Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA. FAU - Bowles, Teylor AU - Bowles T AD - Department of Obstetrics & Gynecology, University of Mississippi Medical Center, 2500 North State St, Jackson, MS, 39216, USA. FAU - Williams, Jan Michael AU - Williams JM AD - Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, USA. FAU - Kyle, Patrick B AU - Kyle PB AD - Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA. FAU - Dumas, John Polk AU - Dumas JP AD - Department of Obstetrics & Gynecology, University of Mississippi Medical Center, 2500 North State St, Jackson, MS, 39216, USA. FAU - Araji, Sarah AU - Araji S AD - Department of Obstetrics & Gynecology, University of Mississippi Medical Center, 2500 North State St, Jackson, MS, 39216, USA. FAU - Wallace, Kedra AU - Wallace K AUID- ORCID: 0000-0003-4511-0046 AD - Department of Obstetrics & Gynecology, University of Mississippi Medical Center, 2500 North State St, Jackson, MS, 39216, USA. kwallace2@umc.edu. LA - eng GR - DK109133/DK/NIDDK NIH HHS/United States GR - P01HL51971/HL/NHLBI NIH HHS/United States GR - P20 GM104357/GM/NIGMS NIH HHS/United States GR - P20 GM103476/GM/NIGMS NIH HHS/United States GR - P20 GM121334/GM/NIGMS NIH HHS/United States GR - P01 HL051971/HL/NHLBI NIH HHS/United States GR - T32 HL105324/HL/NHLBI NIH HHS/United States GR - R01 DK109133/DK/NIDDK NIH HHS/United States GR - R01 MH116027/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200924 PL - England TA - Biol Sex Differ JT - Biology of sex differences JID - 101548963 RN - 0 (Biomarkers) RN - 0 (Endoglin) RN - 0 (Eng protein, rat) RN - EC 2.7.10.1 (Flt1 protein, rat) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1) SB - IM MH - Animals MH - Animals, Newborn MH - Biomarkers/blood/urine MH - Birth Weight MH - Blood Pressure MH - Endoglin/genetics/*metabolism MH - Female MH - *HELLP Syndrome MH - Kidney/*cytology MH - Kidney Diseases/*etiology/pathology MH - Pregnancy MH - Rats MH - Rats, Sprague-Dawley MH - *T-Lymphocytes, Regulatory MH - Vascular Endothelial Growth Factor Receptor-1/genetics/*metabolism PMC - PMC7517692 COIS- The authors declare that they have no competing interests. EDAT- 2020/09/26 06:00 MHDA- 2021/08/05 06:00 PMCR- 2020/09/24 CRDT- 2020/09/25 05:32 PHST- 2020/02/01 00:00 [received] PHST- 2020/09/16 00:00 [accepted] PHST- 2020/09/25 05:32 [entrez] PHST- 2020/09/26 06:00 [pubmed] PHST- 2021/08/05 06:00 [medline] PHST- 2020/09/24 00:00 [pmc-release] AID - 10.1186/s13293-020-00331-6 [pii] AID - 331 [pii] AID - 10.1186/s13293-020-00331-6 [doi] PST - epublish SO - Biol Sex Differ. 2020 Sep 24;11(1):54. doi: 10.1186/s13293-020-00331-6.