Increased urinary levels of podocyte glycoproteins, matrix metallopeptidases, inflammatory cytokines, and kidney injury biomarkers in women with preeclampsia

Abstract

To investigate kidney injury in preeclampsia, we analyzed 14 biomarkers in urine specimen from 4 groups of pregnant women (normotensive pregnant women and those with pregnancy complicated with chronic hypertension or mild or severe preeclampsia). These biomarkers included 1) podocyte glycoproteins nephrin and podocalyxin, 2) matrix metallopeptidase (MMP)-2 and MMP-9 and their inhibitor tissue inhibitor of metalloproteinase-2, 3) inflammatory molecules and cytokines soluble VCAM-1, TNF-α, soluble TNF receptor receptor-1, IL-6, IL-8, IL-10, and IL-18, and 4) kidney injury biomarkers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1. Postpartum urine specimens (6-8 wk) from normotensive women and those with severe preeclampsia were also evaluated. We found that, first, urine levels of nephrin, MMP-2, MMP-9, and kidney injury molecule-1 were significantly higher before delivery in severe preeclampsia than normotensive groups. The increased levels were all reduced to levels similar to those of the normotensive control group in postpartum specimens from the severe preeclampsia group. Second, soluble VCAM-1, soluble TNF receptor-1, and neutrophil gelatinase-associated lipocalin levels were significantly increased in the severe preeclampsia group compared with the normotensive control group before delivery, but levels of these molecules were significantly reduced in postpartum specimens in both groups. Third, IL-6 and IL-8 levels were not different between preeclampsia and normotensive groups but significantly increased in pregnancy complicated with chronic hypertension. Finally, tissue inhibitor of metalloproteinase-2 and IL-18 levels were not different among the study groups before delivery but were significantly reduced in postpartum specimens from normotensive controls. Our results indicate that the kidney experiences an increased inflammatory response during pregnancy. Most interestingly, tubular epithelial cell injury may also occur in severe preeclampsia. These biomarkers could be used to assess podocyte or tubular injury and kidney inflammatory responses during pregnancy and to evaluate postpartum kidney injury recovery in pregnancy-complicated disorders.

Postpartum evaluation of cardiovascular disease risk for women with pregnancies complicated by hypertension

“…Plasma NGAL concentrations were similar in all women with hypertensive disorders of pregnancy and was not associated with FCVRS. This finding is comparable to a report of urinary NGAL concentrations which were elevated in pregnant women with severe pre-eclampsia compared with women with chronic hypertension and healthy controls but differences had resolved by three to eight weeks postpartum, [30] although urinary and plasma concentrations may not be directly comparable.…”

Role of ESAT-6 in renal injury by regulating microRNA-155 expression via TLR4/MyD88 signaling pathway in mice with Mycobacterium tuberculosis infection

“…Inflammatory factors were used as biomarkers to determine renal injury [42]. Lin et al [43] found that TLR4 and its adaptor MyD88 may have a positive effect on enhancing the expressions of IL-1β and TNF-α, from which we hypothesized that elevated expression of inflammatory factors are correlated with activation of TLR4/MyD88 signaling pathway.…”

Ratio of matrix metalloproteinase-2 to -9 is a more accurate predictive biomarker in women with suspected pre-eclampsia

“…A report by Montagnana et al [12] suggested that MMP-2 levels were significantly higher in pre-eclamptic women, however, MMP-9 levels remained unchanged. Whereas Wang et al [24] found that urine levels of both MMP-2 and MMP-9 were significantly higher before delivery in severe PE cases than normotensive groups. Moreover, Karampas et al [25] found no difference in circulating MMP-9 concentrations between normal and PE pregnancies, which is different from results of our present study.…”