607: Severe blood pressure elevation and adverse outcomes in hypertensive disorders of pregnancy

Abstract Background Pregnancy-related acute kidney injury (Pr-AKI) is associated with maternal and fetal morbidity and mortality. There are few studies focusing on Pr-AKI at high altitude in the literature. Objectives to investigate the incidence, etiology, clinical features and maternal-fetal outcomes of Pr-AKI in women living at high altitude. Methods 6,512 pregnant women attending the Department of Obstetrics & Gynecology at local hospital from January 2015 to December 2018 were screened for Pr-AKI. Patients with serum creatinine above normal range(> 70umol/L) then underwent assessment to confirm the diagnosis of Pr-AKI. AKI was diagnosed and staged based on Kidney Disease Improving Global Outcomes(KDIGO) guideline. Individuals meeting the Pr-AKI criteria were recruited. Their clinical data were recorded and retrospectively analyzed. Results Pr-AKI was identified in 136/6512(2.09 %) patients. Hypertensive disorders of pregnancy(HDP) was the leading cause of Pr-AKI(35.3 %). 4(2.9 %) women died and the majority(86.1 %) had recovered renal function before discharge. Fetal outcomes were confirmed in 109 deliveries with gestational age ≥ 20 weeks. Pre-term delivery occurred in 30(27.3 %) cases and perinatal deaths in 17(15.5 %). The rate of low birth weight infant(LBWI) and intrauterine growth restriction(IUGR) was 22.0 and 10.9 % respectively. 16(14.5 %) infants were admitted to NICU after birth. Patients with HDP had a higher cesarean rate(56.3 %). More IUGR(25.0 %) and LBWI(37.8 %) were observed in their infants with a higher risk of admission to NICU(22.0 %). High altitude might have an adverse impact on HDP-related Pr-AKI patients with earlier terminated pregnancy and more stillbirth/neonatal death. Logistic regression models indicated that uncontrolled blood pressure, high altitude and advanced AKI were associated with adverse fetal outcomes in HDP-related Pr-AKI patients. Conclusions Pr-AKI was not rare in high-altitude regions and caused severe fetal morbidities and mortalities. Uncontrolled blood pressure, high altitude and advanced AKI were all risk factors for adverse fetal outcomes in Pr-AKI patients, especially for those with hypertensive disorders of pregnancy.

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Abstract P242: The Role Of Kappa Opioid Receptors In The Development Of Hypertension And Kidney Injury In Sprague-Dawley Rats

Hypertension ◽

10.1161/hyp.78.suppl_1.p242 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Daria Golosova ◽

Adrian Zietara ◽

Ruslan Bohovyk ◽

Vladislav Levchenko ◽

Alexander Staruschenko

Keyword(s):

Blood Pressure ◽

Sprague Dawley ◽

Glomerular Injury ◽

Kappa Opioid ◽

Injury Score ◽

Calcium Response ◽

Blood Pressure Elevation ◽

Isolated Glomeruli ◽

Pressure Elevation ◽

Sd Rats

The extensive use of opioid-based pain management strongly correlates with poor cardiovascular and cardiorenal outcomes. Our recent studies suggest that treatment with kappa opioid receptor (KOR) agonist BRL 52537 leads to the progression of chronic kidney disease (CKD) and aggravation of salt-sensitive hypertension. We hypothesize that stimulation of KORs leads to blood pressure elevation, albuminuria, and kidney damage in healthy Sprague-Dawley (SD) rats. To characterize the effect of the KOR agonist BRL 52537 on the development of blood pressure and kidney function in vivo , SD rats were treated with a daily i.v. bolus infusion of BRL 52537 or a corresponding vehicle. To test the contribution of KOR stimulation on calcium homeostasis in podocytes, BRL 52537 was used on freshly isolated glomeruli from SD rats. Single-channel analysis was applied to assess the effect of KORs stimulation on TRPC6 channel activity in the human immortalized podocytes. Chronic treatment with BRL 52537 leads to increased mean arterial pressure (88±1 vs 101±4 mmHg, vehicle vs treated, p<0.05), podocyte basal calcium (90±12 vs 216±16 a.u., vehicle vs treated, p<0.05), and GFB impairment in SD rats which is reflected by a transient increase in albumin excretion (Alb/cre ratio 0.35±0.1 vs 0.72±0.2, vehicle vs treated, p<0.05). Cumulative probability distribution analysis of the glomerular injury score revealed a rightward shift toward a high glomerular injury score in the group treated with BRL 52537 (p<0.05). Angiotensin II level was higher in a BRL-treated group (156±17 vs 232±59 pmol, vehicle vs treated, p=0.065); however, it did not reach a statistical difference. Acute application of BRL 52537 resulted in sustained calcium response (0.23±0.01 a.u., Fluo4/FuraRed, maximum calcium response) in freshly isolated glomeruli from SD rats. Furthermore, patch-clamp experiments in human immortalized podocytes (cell-attached configuration) revealed that BRL 52537 activated TRPC6 channels. Taken together, these data support the hypothesis that administration of opioids in SD rats leads to activation of the KOR/TRPC6 pathway, which in turn led to glomerular filtration barrier impairment, increased glomerular damage, and blood pressure elevation.

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