Morphologic changes in the renal glomerulus and the juxtaglomerular apparatus in human preeclampsia

Hill, Prudence A.; Fairley, Kenneth F.; Kincaid‐Smith, Priscilla; Zimmerman, Matthew C.; Ryan, Graeme B.

doi:10.1002/path.1711560404

Cited by 20 publications

(9 citation statements)

References 22 publications

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“…In the mouse model, the increase in renin expression is in the fetal placental tissue as opposed to the maternal placental tissue, i.e., the decidua in human preeclampsia. Renal renin juxtaglomerular cell granularity in manifest preeclampsia is decreased (57), which is consistent with the 2K-1C Goldblatt model analogy for preeclampsia. We are proposing that, after activation of the decidual RAS, a modest increase in ANG II entering the systemic circulation results in the vascular maladaptation seen in preeclampsia.…”

Section: Invited Reviewsupporting

confidence: 82%

“…These observations suggest that after the establishment of increased sensitivity to ANG II, renal renin and adrenal aldosterone secretions are apparently suppressed. The renal renin juxtaglomerular cell granularity in manifest preeclampsia is decreased (57), which is consistent with the decrease in renal renin secretion. Maternal circulating renin in human pregnancy represents renal renin because it responds appropriately to renal-type physiological stimuli (22).…”

Section: The Ras In Preeclampsiasupporting

confidence: 71%

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Role of the renin-angiotensin system in the pathogenesis of preeclampsia

Shah

2005

American Journal of Physiology-Renal Physiology

128

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Shah, Dinesh M. Role of the renin-angiotensin system in the pathogenesis of preeclampsia. Am J Physiol Renal Physiol 288: F614 -F625, 2005; doi:10.1152/ ajprenal.00410.2003.-Preeclampsia is a hypertensive disorder unique to pregnancy with consistent involvement of the kidney. The renin-angiotensin system (RAS) has been implicated in the pathogenesis of preeclampsia. In the gravid state, in addition to the RAS in the kidney, there is a tissue-based RAS in the uteroplacental unit. Increased renin expression observed both in human preeclampsia and in a transgenic mouse model with a human preeclampsia-like syndrome supports the concept that activation of the uteroplacental RAS, with angiotensin II entering the systemic circulation, may mediate the pathogenesis of preeclampsia. A novel disease paradigm of the two-kidney one-clip (2K-1C) Goldblatt model is presented for preeclampsia, wherein the gravid uterus is the clipped "kidney" and the two maternal kidneys represent the unclipped kidney. Validation of the 2K-1C Goldblatt model analogy requires evidence of elevated angiotensin II in the peripheral circulation before vascular maladaptation in preeclampsia. Convincing evidence of the elevation of angiotensin II in preeclampsia does not exist despite the fact that much of vascular pathogenesis appears to be due to angiotensin type I (AT 1) receptor activation. Vascular maladaptation with increased vasomotor tone, endothelial dysfunction, and increased sensitivity to angiotensin II and norepinephrine in manifest preeclampsia may be explained on the basis of angiotensin II-mediated mechanisms. Recently, novel angiotensin II-related biomolecular mechanisms have been described in preeclampsia. These include AT 1 and bradykinin B2 receptor heterodimerization and the production of an autoantibody against AT1. Various organ systems with a predilection for involvement in preeclampsia are each a site of a tissue-based RAS. How angiotensin II-mediated mechanisms may explain the primary clinical-pathological features of preeclampsia is described. Future investigations are proposed to more precisely define the role of activation of the uteroplacental RAS in the mechanisms underlying preeclampsia.HYPERTENSIVE DISORDERS COMPLICATE approximately 5-7% of all pregnancies (35a). These disorders include 1) chronic hypertension of whatever origin, including essential hypertension and chronic renal disease; 2) gestational hypertension, a hypertensive disorder occurring in pregnancy without multisystem involvement; 3) preeclampsia syndrome superimposed on chronic hypertension; 4) preeclampsia syndrome occurring de novo and only in the first pregnancy; and 5) preeclampsia syndrome occurring in a subsequent pregnancy and/or recurring with an underlying susceptibility state.Preeclampsia is a unique syndrome of pregnancy characterized by hypertension, proteinuria, and, frequently, edema. Several pathophysiological mechanisms have been implicated in the development of preeclampsia. These include endothelial dysfunction (36), an inflammatory p...

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Section: Invited Reviewsupporting

confidence: 82%

Section: The Ras In Preeclampsiasupporting

confidence: 71%

Role of the renin-angiotensin system in the pathogenesis of preeclampsia

Shah

2005

American Journal of Physiology-Renal Physiology

128

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“…The degree of increase in renin gene expression is much higher in this model than in the human syndrome. The renal renin juxtaglomerular cell granularity in manifest preeclampsia is decreased [31], which is consistent with the 2K-1C Goldblatt model analogy for preeclampsia. Given the evidence that pro-gesterone regulates RAS, we suggest that the placental progesterone may be one of the factors that signals the maternal side to activate the decidual RAS.…”

Section: Goldblatt Model Analogysupporting

confidence: 81%

“…These observations suggest that, after the establishment of increased sensitivity to Ang II, renal renin and adrenal aldosterone secretions are apparently suppressed. The renal renin juxtaglomerular cell granularity in manifest preeclampsia is decreased [31]. The maternal circulating renin in human pregnancy represents renal renin because it responds appropriately to the renal-type physiologic stimuli [32].…”

Section: Circulating Ras In Preeclampsiamentioning

confidence: 99%

The role of RAS in the pathogenesis of preeclampsia

Shah

2006

Current Science Inc

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Preeclampsia is a hypertensive disorder that is unique to pregnancy, with consistent involvement of the kidney. The renin-angiotensin system (RAS) has been implicated in the pathogenesis of preeclampsia. In the gravid state, in addition to the RAS in the kidney, there is a tissue-based RAS in the uteroplacental unit. Increased renin expression in human preeclampsia and in transgenic mouse models with a human preeclampsia-like syndrome shows that activation of the uteroplacental RAS, with angiotensin II entering the systemic circulation, may mediate the pathogenesis of preeclampsia. Vascular maladaptation in preeclampsia with increased vasomotor tone, endothelial dysfunction, and increased sensitivity to angiotensin II and norepinephrine in manifest preeclampsia may be explained on the basis of angiotensin II-mediated mechanisms through angiotensin receptor type I (AT1) activation. Recently, novel angiotensin II-related biomolecular mechanisms have been described in preeclampsia. These include AT1 and bradykinin B2 receptor heterodimerization and the production of autoantibody against AT1. Various organ systems with predilection for involvement in preeclampsia are sites of tissue-based RAS. Angiotensin II-mediated mechanisms may explain the primary clinicopathologic features of preeclampsia. In this review, these various aspects are critically examined and an integrated concept on the role of RAS in preeclampsia is presented.

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“…The observed coagulation activation in the HELLP patients may, however, still result in intravascular fibrin deposition, in particular if the stimulus for activation continues for a period of days. Indeed fibrin deposits have been observed in the liver, kidney and placenta of these patients (Aarnoudse et al 1986; Hill et al 1989; Wallenburg 1987). Therefore, it is interesting to speculate that compensated DIC is an important causal factor in the liver‐, kidney‐and placental dysfunction seen in the syndrome.…”

Section: Discussionmentioning

confidence: 99%

Coagulation studies in the syndrome of haemolysis, elevated liver enzymes and low platelets

Boer¹,

Büller²,

Cate³

et al. 1991

BJOG

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Summary. The presence of disseminated intravascular coagulation (DIC) in the syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP) is debated. We assessed the occurrence of decompensated and compensated DIC (using predefined criteria) in 15 consecutive nulliparous pregnant patients with gestastional hypertension combined with the HELLP syndrome and in 12 consecutive nulliparous controls with pregnancy induced hypertension (PIH) but without the HELLP syndrome. A combination of routine coagulation assays revealed the absence of decompensated DIC in all studied patients. However, using more specific and sensitive coagulation assays, compensated DIC was observed in all HELLP patients and in three patients in the control group. The mean values of antithrombin III, thrombin‐antithrombin III complexes and protein C in the HELLP and the control group were 66 vs 87% (P=0.0004), 21 vs 8 ng/ml (P=0.0008) and 57 vs 90% (P=0.0018) respectively. We conclude that HELLP patients show evidence of compensated DIC which may have pathophysiological significance for the observed organ damage.

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Morphologic changes in the renal glomerulus and the juxtaglomerular apparatus in human preeclampsia

Cited by 20 publications

References 22 publications

Role of the renin-angiotensin system in the pathogenesis of preeclampsia

Role of the renin-angiotensin system in the pathogenesis of preeclampsia

The role of RAS in the pathogenesis of preeclampsia

Coagulation studies in the syndrome of haemolysis, elevated liver enzymes and low platelets

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