Course of preeclamptic glomerular injury after delivery

Hladunewich, Michelle A.; Myers, B. D.; Derby, Geraldine C.; Blouch, Kristina; Druzin, Maurice L.; Deen, WM; Naimark, David; Lafayette, Richard A.

doi:10.1152/ajprenal.00470.2007

Cited by 42 publications

(35 citation statements)

References 31 publications

(48 reference statements)

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“…The number of these cells declines rapidly after delivery, in parallel with the clinical recovery of the patient [34]. The functional manifestations of glomerular endothelial cell injury also largely resolve within the first postpartum month [35]. The normalization of endothelial vasoactive substances that precedes clinical recovery in preeclamptic women after delivery further strengthens the concept of postpartum endothelial recovery [36].…”

Section: Discussionmentioning

confidence: 80%

Differential Expression of Vegfr-2 and Its Soluble Form in Preeclampsia

et al. 2012

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Background Several studies have suggested that the main features of preeclampsia (PE) are consequences of endothelial dysfunction related to excess circulating anti-angiogenic factors, most notably, soluble sVEGFR-1 (also known as sFlt-1) and soluble endoglin (sEng), as well as to decreased PlGF. Recently, soluble VEGF type 2 receptor (sVEGFR-2) has emerged as a crucial regulator of lymphangiogenesis. To date, however, there is a paucity of information on the changes of VEGFR-2 that occur during the clinical onset of PE. Therefore, the aim of our study was to characterize the plasma levels of VEGFR-2 in PE patients and to perform VEGFR-2 immunolocalization in placenta. Methodology/Principal findings By ELISA, we observed that the VEGFR-2 plasma levels were reduced during PE compared with normal gestational age matched pregnancies, whereas the VEGFR-1 and Eng plasma levels were increased. The dramatic drop in the VEGFR-1 levels shortly after delivery confirmed its placental origin. In contrast, the plasma levels of Eng and VEGFR-2 decreased only moderately during the early postpartum period. An RT-PCR analysis showed that the relative levels of VEGFR-1, sVEGFR-1 and Eng mRNA were increased in the placentas of women with severe PE. The relative levels of VEGFR-2 mRNA as well as expressing cells, were similar in both groups. We also made the novel finding that a recently described alternatively spliced VEGFR-2 mRNA variant was present at lower relative levels in the preeclamptic placentas. Conclusions/Significance Our results indicate that the plasma levels of anti-angiogenic factors, particularly VEGFR-1 and VEGFR-2, behave in different ways after delivery. The rapid decrease in plasma VEGFR-1 levels appears to be a consequence of the delivery of the placenta. The persistent circulating levels of VEGFR-2 suggest a maternal endothelial origin of this peptide. The decreased VEGFR-2 plasma levels in preeclamptic women may serve as a marker of endothelial dysfunction.

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Section: Discussionmentioning

confidence: 80%

Differential Expression of Vegfr-2 and Its Soluble Form in Preeclampsia

et al. 2012

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“…Previous studies have shown that glomerular damage and proteinuria often are extensive during a preeclamptic pregnancy (20,21) but normalize soon after birth in the majority (22). In a small subset of patients, the resolution might, however, take years (23), and as described earlier, follow-up studies have suggested that it persists in 31% of women.…”

Section: Discussionmentioning

confidence: 84%

Preeclampsia and Prevalence of Microalbuminuria 10 Years Later

Sandvik

Hallan

Svarstad

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives A recent meta-analysis found that about 30% of women with a previous preeclamptic pregnancy had persistent microalbuminuria at follow-up. The analysis was, however, based on small studies, and more data are needed.Design, setting, participants, & measurements Using data from the Medical Birth Registry in Norway, this study identified women with or without preeclampsia in their first pregnancy 9-11 years previously (1998)(1999)(2000). Women with diabetes, rheumatic disease, essential hypertension, or renal disease before first pregnancy and/or preeclampsia in later pregnancies were excluded. Eighty-nine women with and 69 women without preeclampsia participated in the study. Urinary albumin-to-creatinine ratio (ACR) was measured in three morning urine samples. Estimated GFR (eGFR) was calculated using the CKD-Epidemiology Collaboration formula.Results Median urinary ACR in follow-up urine samples was 0.53 mg/mmol for women with and 0.50 mg/mmol for women without preeclampsia (P=0.54). Only one woman (1%) with previous preeclampsia had urinary ACR .2.5 mg/mmol in two of three urine samples. Preeclampsia was not associated with urinary ACR above the 75th percentile. Women with preeclampsia did not have significantly higher eGFR than women without preeclampsia (107.9 versus 104.9 ml/min per 1.73 m 2 ; P=0.12), but preterm preeclampsia was significantly associated with eGFR above the 75th percentile (P=0.03).Conclusions In this population-based study of otherwise healthy women, preeclampsia 10 years earlier was not associated with increased risk of persisting microalbuminuria. Estimated GFR was not significantly different between women with and those without preeclampsia, but preterm preeclampsia was associated with high normal eGFR.

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“…Using different methodologies, Lafayette et al (106) and Hladunewich et al (90) also concluded that there was ϳ50% reduction of K f in women with PE compared with control pregnant subjects 1 day after delivery, which fully accounted for the comparable percentage decrease in GFR in their study because, in contrast to the majority of other investigations, they did not observe impairment of RPF in PE. In the aforementioned studies, impaired K f in PE women returned to the normal range by 5 wk postpartum (90) or by Ն5 mo after delivery (133).…”

Section: Renal Plasma Flow and Glomerular Filtration In Preeclampsiamentioning

confidence: 87%

The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin?

Conrad

Davison

2014

American Journal of Physiology-Renal Physiology

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Conrad KP, Davison JM. The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin?. Am J Physiol Renal Physiol 306: F1121-F1135, 2014. First published March 19, 2014 doi:10.1152/ajprenal.00042.2014.-During the first trimester of human pregnancy, the maternal systemic circulation undergoes remarkable vasodilation. The kidneys participate in this vasodilatory response resulting in marked increases in renal plasma flow (RPF) and glomerular filtration rate (GFR). Comparable circulatory adaptations are observed in conscious gravid rats. Administration of the corpus luteal hormone relaxin (RLN) to nonpregnant rats and humans elicits vasodilatory changes like those of pregnancy. Systemic and renal vasodilation are compromised in midterm pregnant rats by neutralization or elimination of circulating RLN and in women conceiving with donor eggs who lack a corpus luteum and circulating RLN. Although RLN exerts both rapid (minutes) and sustained (hours to days) vasodilatory actions through different molecular mechanisms, a final common pathway is endothelial nitric oxide. In preeclampsia (PE), maternal systemic and renal vasoconstriction leads to hypertension and modest reduction in GFR exceeding that of RPF. Elevated level of circulating soluble vascular endothelial growth factor receptor-1 arising from the placenta is implicated in the hypertension and disruption of glomerular fenestrae and barrier function, the former causing reduced K f and the latter proteinuria. Additional pathogenic factors are discussed. Last, potential clinical ramifications include RLN replacement in women conceiving with donor eggs and its therapeutic use in PE. Another goal has been to apply knowledge gained from investigating circulatory adaptations in pregnancy toward identifying and developing novel therapeutic strategies for renal and cardiovascular disease in the nonpregnant population. So far, one candidate to emerge is RLN and its potential therapeutic use in heart failure. renal hemodynamics; glomerular filtration; osmoregulation; relaxin; nitric oxide; assisted reproductive technology; glomerular endotheliosis; soluble vascular endothelial growth factor receptor-1; heart failure Renal Plasma Flow and Glomerular Filtration in Normal PregnancyMARKED VASODILATION OF THE MATERNAL CIRCULATION occurs in the first trimester of human pregnancy. Consequently, there is a precipitous and profound decline in systemic vascular resistance (SVR) that in turn abets a reciprocal increase in cardiac output (CO) of ϳ40% or 2 l/min lasting throughout pregnancy (23,163). Vasodilation of nonreproductive organs like the kidneys accounts mostly for the early gestational fall in SVR and rise in CO. The fall in SVR is nearly offset by the rise in CO; hence, mean arterial pressure (MAP) declines, but only modestly, by 5-10 mmHg (23,38,163). Although counterintuitive, this metamorphosis of the maternal circulation is virtually complete by the end of the first or beginning of the second trimester, when fetal crown rump length and place...

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Course of preeclamptic glomerular injury after delivery

Cited by 42 publications

References 31 publications

Differential Expression of Vegfr-2 and Its Soluble Form in Preeclampsia

Differential Expression of Vegfr-2 and Its Soluble Form in Preeclampsia

Preeclampsia and Prevalence of Microalbuminuria 10 Years Later

The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin?

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