Acute Kidney Injury in Pregnancy and HELLP Syndrome

Abstract

INTRODUCTIONAcute kidney injury (AKI) during pregnancy is associated with rates of maternal mortality and fetal loss that range from 30–60%. Given that preeclampsia (PE) and HELLP syndrome are among the more common pregnancy‐related causes of AKI we set out to determine the prevalence of AKI in patients with PE or HELLP at our University. As maternal mortality in women with HELLP is often a result of either renal or neuro complications we also wanted to create AKI in our already established pregnant animal model of HELLP in order to study the pathophysiological mechanisms associated with these syndrome.METHODSWe conducted an IRB approved retrospective chart review of women with a diagnosis of PE or HELLP between January 2000 – December 2010 at the University of MS Medical Center to determine the incidence of AKI (defined as creatinine ≥ 1.2mg/dL). On gestational day (GD) 12, miniosmotic pumps infusing sFlt‐1 and sEng were placed into rats to induce HELLP (n=7). A subset of HELLP (n=4) and NP rats (n=3) underwent bilateral renal ischemia‐reperfusion surgery for 45 minutes on GD18 to create AKI. All rats had carotid catheters inserted for mean arterial pressure measurement; rats without pumps or AKI surgery served as NP controls (n=4). On GD19, MAP was measured, plasma collected for creatinine (pCr) and kidneys collected for either flow cytometry or trichrome staining. Statistical Analysis was done with Student's T test or ANOVA with Bonferroni's post‐hoc analysis.RESULTSOf the 1354 patients included in the study (HELLP n=426; PE n= 928), 75 patients had AKI defined as creatinine ≥ 1.2mg/dL. Women with HELLP had significantly higher peak creatinine levels compared to women with PE (P=0.02) and were more likely to develop AKI (P=0.01) and had more severe morbidities compared to women with PE (P=0.01) and women, PE or HELLP, who did not develop AKI (P=0.01). HELLP rats had a significantly higher plasma creatinine (pCr) level compared to NP rats (1±0.06 vs 1.8±0.3; P=0.05). When rats were subjected to AKI surgery, pCr significantly increased in NP+AKI (2.9±0.4; P=0.03) and in HP+AKI (3.8 ±0.3; P=0.01) relative to NP and HELLP control rats. Mean arterial pressure was found to be significantly different among the groups with all groups being significantly increased relative to NP rats (100.5±1.32mmHg) and each other (P<0.01) with the exception of HELLP vs NP+AKI rats which were not significantly different when compared to each other (121±3.5 vs 119.3±2.2mmHg; P=0.71). Lactate dehydrogenase was significantly increased in all groups respective to NP rats (P<0.01). As we have previously reported that HELLP is associated with renal inflammation we also measured renal CD4+ T cells and saw that HELLP+AKI rats had significantly more CD4+ T cells relative to all groups (37.8±9%; P<0.01). Finally, when renal histology was examined there were no observable differences in the renal cortex between groups, however HELLP+AKI rats had more renal medullary interstitial fibrosis compared to NP+AKI rats.DISCUSSIONThese results suggest that women with HELLP are more susceptible to the development of AKI and have more maternal morbidities. We were able to successfully create an animal model of HELLP+AKI and NP+AKI. Studies are currently being conducted in our lab to determine the full extent of oxidative stress, inflammation and progression to chronic kidney disease. Future studies will specifically target T cells with the hope of preventing hypertension and the progression of renal injury in the AKI model.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.