Glomerular Endotheliosis Research Articles

The Glomerular Injury of Preeclampsia

Preeclampsia is a pregnancy-specific disorder that complicates approximately 5% of all pregnancies, making it perhaps the most common glomerular disease in the world. It is characterized by new-onset hypertension and proteinuria, in association with a characteristic glomerular lesion, endotheliosis. "Glomerular endotheliosis" represents a specific variant of thrombotic microangiopathy that is characterized by glomerular endothelial swelling with loss of endothelial fenestrae and occlusion of the capillary lumens. Associated thrombosis is unusual. Recent evidence suggests that this unusual glomerular lesion is mediated by a soluble vascular endothelial growth factor receptor that deprives glomerular endothelial cells of the vascular endothelial growth factor that they require, leading to cellular injury and disruption of the filtration apparatus with subsequent proteinuria. This review summarizes the histologic changes and the pathogenesis of the glomerular lesions of preeclampsia.

Antepartum percutaneous renal biopsy

Objective To assess the value and adverse effects of an ultrasound-guided renal biopsy technique in women with normal and pathologic pregnancies. Method Biopsy samples were taken from 36 women with hypertensive disease (28 with pre-eclampsia) and 18 healthy pregnant women using a thin needle and an ultrasound-guided biopsy device. Results Glomerular endotheliosis, a structural change typical of pre-eclampsia, was found in all hypertensive women, but it was more pronounced in the 28 pre-eclamptic women than in the 8 women with nonproteinuric hypertension. A similar change, however, was seen in 11 of the 18 controls. One serious adverse event occurred, retroperitoneal hematoma, in the woman with the most severe pre-eclampsia. Conclusion Glomerular endotheliosis is not to be considered pathognomonic for pre-eclampsia. Few complications followed renal biopsy in this study, but complications arose in the sickest patient. It is probably not advisable to perform antepartum renal biopsies in pregnant women with a rapidly deteriorating renal function and swollen kidneys. In these women, the biopsy does not facilitate diagnosis and is hazardous.

Emerging Roles of Antiangiogenic and Angiogenic Proteins in Pathogenesis and Prediction of Preeclampsia

Hypertensive disorders are a major cause of maternal and fetal death, especially in developing nations, with the pregnancy-specific disease preeclampsia-eclampsia responsible for most of this mortality. Preeclampsia, recognized by ancient Greeks, was only sporadically investigated until late last century, current literature still labeling this disorder a “disease of theories.” Thus, not surprisingly, we have started the new millennium unable to predict or prevent preeclampsia, and management strategies remain but supportive, with pregnancy termination still the only definitive “therapy.” This may be about to change, as focused research, mainly in the past decade, has resulted in dramatic progress regarding pathogenesis of disease manifestations and risk assessment, while investigators have begun designing and testing definitive therapy.1 There are still a myriad of uncertainties and unanswered questions to address, but here we summarize the extent of 1 new and exciting chapter in preeclampsia research: the roles of angiogenic and antiangiogenic factors, to which an article in this issue by Rana and colleagues,2 contributes. A landmark report published in 2003 set the stage for all that followed.3 Dr Karumanchi’s laboratory, previously involved in renal cancer research, changed its focus to the kidney in preeclampsia. Using microarray chip technology, they probed gene expression profiles in placentas of women with preeclampsia and those with uncomplicated pregnancies. Of course many differences were noted, but one that caught the investigators’ attention was upregulation of the mRNA for the antiangiogenic protein soluble fms-like tyrosine kinase 1 (abbreviated as sFlt-1 or sVEGFR-1) in placentas from women with preeclampsia. Aware that de novo hypertension and proteinuria were 2 disturbing side effects of certain antiangiogenic compounds tested in cancer patients, these …

Pathophysiology of the Clinical Manifestations of Preeclampsia

Five to 7% of all pregnancies are complicated by preeclampsia. Proteinuria and hypertension dominate the clinical picture, because the chief target organ is the kidney (glomerular endotheliosis). The pathogenesis of preeclampsia is complex; numerous genetic, immunologic, and environmental factors interact. It has been suggested that preeclampsia is a two-stage disease (1). The first stage is asymptomatic, characterized by abnormal placental development during the first trimester resulting in placental insufficiency and the release of excessive amounts of placental materials into the maternal circulation. This in turn leads to the second, symptomatic stage, wherein the pregnant woman develops characteristic hypertension, renal impairment, and proteinuria and is at risk for the HELLP syndrome (hemolysis, elevated liver function enzymes and low platelets), eclampsia, and other end-organ damage. This review focuses on the pathophysiology of stages 1 and 2 and then considers the potential that changes in soluble angiogenic factors may underlie much of the disease process. On the basis of the observation that the only definitive cure for preeclampsia is delivery of the placenta and that women who experience a molar pregnancy, in which a placenta develops without a fetus, frequently develop severe preeclampsia, it is reasonable to assume that the placenta plays a central role in the pathogenesis of the disease. Pathologic examination of placentas from preeclamptic pregnancies generally reveals placental infarcts and sclerotic narrowing of arteries and arterioles, with characteristic diminished endovascular invasion by cytotrophoblasts and inadequate remodeling of the uterine spiral arterioles (2). Although gross pathologic changes are not always seen in the placentas of women with preeclampsia, placental profiles including abnormal uterine artery Doppler and placental morphology have been used to identify a subset from a cohort of high-risk women who go on to develop the syndrome (3). Uterine artery Doppler studies that assess the pulsatility index (PI) reveal increased …

A novel renal perspective of preeclampsia: a look from the podocyte

Sir, Preeclampsia (PE) is the most severe hypertensive complication of pregnancy. Onset of proteinuria is the main criterion for diagnosis of PE. Examination of renal biopsies of women with PE shows a pathognomonic lesion known as glomerular endotheliosis (GEN); nonetheless, GEN, from a low to a severe degree, has also been observed in women with gestational hypertension without proteinuria and in healthy pregnant women. Hence, alterations of renal function in women with PE can be attributed to a component of the glomerular filtration barrier (GFB) different from the glomerular endothelium. We propose that proteinuria in women with PE is due to direct injury of podocytes. The GFB possesses three components: the glomerular endothelium, the glomerular basement membrane and epithelial cells known as podocytes. Podocytes assemble forming the slit diaphragm (SD). The SD is located between the foot processes of the podocytes and is composed of a protein complex including Nephrin, NEPH1, NEPH2, FAT1, P-cadherin, Podocin and CD2AP. These proteins interact with each other by way of the foot processes of other podocytes, forming a critical pathway of the GFB. Hence, down-regulation of one of these proteins could be involved in the appearance and development of proteinuria in women with PE. The function of the podocyte and the SD depends on the physiological concentrations of circulating factors, such as vascular endothelial growth factor (VEGF) and its antagonist, the soluble receptor fms-like tyrosine kinase 1 (sFlt-1). Based on findings stating that, (i) GEN is present in women with PE and also in pregnant women without proteinuria, [1] (ii) physiological concentrations of VEGF are important for podocyte homeostasis and survival, [2] (iii) VEGF is important in maintaining of the SD by regulating nephrin expression, [3] (iv) sFlt-1 is a circulating antiangiogenic factor that antagonizes VEGF by binding to it and inactivating it, therefore inhibiting the action of VEGF on the SD, (v) there is an elevated concentration of sFlt-1 in the serum of women with PE as opposed to normotensive pregnant women, [4] (vi) elevated concentrations of sFlt-1 down-regulate the expression of proteins of the SD such as nephrin, [3] and (vii) down-regulation of nephrin expression leads to proteinuria, [5] we propose that proteinuria in patients with PE is mediated not only by endothelium alterations described classically, but also by disturbances of podocyte biology including impaired survival, enhanced apoptosis and down-regulation of nephrin and/or other key proteins of the SD.

Circulating Levels of the Antiangiogenic Marker Soluble FMS-Like Tyrosine Kinase 1 Are Elevated in Women With Pregestational Diabetes and Preeclampsia

Preeclampsia is characterized by the development of proteinuria and hypertension after 20 weeks gestation, and it is associated with maternal and fetal morbidity. Preeclampsia affects ∼5% of pregnancies, though women with preexisting diabetes are three to four times more likely to develop preeclampsia (1). Preeclampsia is associated with altered angiogenic factors, including increased levels of circulating soluble FMS-like tyrosine kinase 1 (sFlt1) and reduced levels of vascular endothelial growth factor and placental growth factor (PlGF). Hypertension and proteinuria of preeclampsia may be caused by an imbalance of these angiogenic factors (2–10). Circulating sFlt1, an antiangiogenic protein, binds to proangiogenic proteins, vascular endothelial growth factor, and PlGF, preventing their interaction with endothelial cell receptors and inducing endothelial dysfunction. Rats given sFlt1 develop proteinuria, hypertension, and glomerular endotheliosis, which are hallmarks of preeclampsia (3). Alterations in sFlt1 and PlGF are observed several weeks before symptoms (2). It is unknown whether alterations in sFlt1 and PlGF are present in women with diabetes who then develop preeclampsia or whether a different pathway is responsible. Ultimately, it would be helpful to have a way to diagnose and predict preeclampsia in women with pregestational diabetes, as they frequently have preexisting hypertension and/or proteinuria, which make it difficult to differentiate superimposed preeclampsia. We evaluated a small group of women with diabetes and compared levels of sFlt1 and PlGF at delivery in both those who developed preeclampsia and those …

Renal function during normal pregnancy and preeclampsia

Glomerular filtration rate and renal plasma flow increase by 40 to 65 and 50 to 85%, respectively, during normal pregnancy in women. Studies using the gravid rat as a model have greatly enhanced our understanding of mechanisms underlying these remarkable changes in the renal circulation during gestation. Hyperfiltration is largely due to increased renal plasma flow, the latter attributable to profound reductions in both the renal afferent and efferent arteriolar resistances. The ovarian hormone, relaxin, mediates renal vasodilation during pregnancy. Relaxin increases vascular gelatinase activity, thereby converting big ET to ET(1-32), which leads to renal vasodilation, hyperfiltration and reduced myogenic reactivity of small renal arteries via the endothelial ET(B) receptor and nitric oxide. Serum concentration of uric acid falls during normal pregnancy as a consequence of increased GFR and/or reduced proximal tubular reabsorption. The elevated urinary excretion of protein during pregnancy is secondary to increased GFR, reduced proximal tubular reabsorption, and perhaps alteration in the electrostatic charge of the glomerular filter. Whether the tubular secretion of Tamm-Horsfall protein increases during normal pregnancy is uncertain. In most women with preeclampsia, renal plasma flow and glomerular filtration rate are at most only modestly decreased as a consequence of increased afferent arteriolar resistance and/or reduced ultrafiltration coefficient. Serum uric acid concentrations are increased mainly as a consequence of reduced renal clearance. Reduced GFR leads to decreased filtered load of uric acid, and plasma volume contraction contributes to increased proximal tubular reabsorption coupled to sodium. The increase in urinary protein excretion in preeclampsia occurs secondary to alterations in the size and/or charge selectivity of the glomerular filter, possible increases in glomerular capillary pressure, and compromise of proximal tubular reabsorption. The renal histologic lesion characteristic of preeclampsia is termed "glomerular endotheliosis". Recent evidence suggests that anti-angiogenic factors emanating from the placenta in preeclampsia contribute to glomerular endotheliosis, proteinuria, and hypertension during disease.

Soluble endoglin (sEng) joins the soluble fms-like tyrosine kinase (sFlt) receptor as a pre-eclampsia molecule

Pre-eclampsia is a devastating disease of late (after week 20) pregnancy. The condition features hypertension, proteinuria, premature labor, haemolysis, liver abnormalities, thrombocytopenia (HELLP syndrome), seizures (eclampsia) and death [1]. Both mothers and children, if they survive delivery, can expect subsequent increased cardiovascular risk in the future. Preeclampsia affects about 5% of the pregnancies in affluent societies; in the rest of the world, the incidence is higher. Suffice it to say, pre-eclampsia is a major world health problem. The group led by Anand Karumanchi et al. [2] has made major contributions in terms of our understanding pre-eclampsia. They showed that preeclampsia is associated with a circulating aberrant splice variant of the vascular endothelial growth factor (VEGF) receptor fms-like tyrosine kinase (Flt). This receptor is also an important target for placental growth factor (PLGF). The soluble fms-like tryrosine kinase (sFlt) receptor is a splice variant of the VEGF receptor Flt. The Karumanchi group showed that patients with pre-eclampsia have increased circulating levels of sFlt that putatively catches VEGF and PLGF before these mediators can interact with their ligands (Figure 1, panel A). As a result, endothelial and, particularly, placental (trophoblast) growth could be stunted, causing pre-eclamspia. The hypothesis was underscored by in vitro and in vivo experiments. Serum from preeclampstic patients inhibited tube formation by endothelial cells in culture. Giving sFlt to rats caused hypertension, proteinuria and glomerular endotheliosis. Subsequently, the group collaborated with clinical investigators who had performed a randomized trial of calcium supplementation in women at risk for preeclampsia. The calcium story was negative; however, the women developing pre-eclampsia in these studies had increased circulating sFlt levels and decreased PLGF and VEGF concentrations [3]. The data appeared convincing [4].

A Case of “Pure” Preeclampsia With Nephrotic Syndrome Before 15 Weeks of Gestation in a Patient Whose Renal Biopsy Showed Glomerular Capillary Endotheliosis

A 35-year-old Japanese woman for whom a previous health checkup showed normal blood pressure and urinalysis results without serological abnormalities developed nephrotic syndrome with severe hypertension at 15 gestational weeks. The renal biopsy performed at 17 weeks of gestation showed severe glomerular capillary endotheliosis. By means of electron microscopy, no electron-dense deposits were observed in glomeruli, and foot-process arrangement was normal. Histological findings indicated the patient's glomerular damage was caused by the mechanisms of preeclampsia. The patient underwent an elective abortion at 18 weeks of gestation. Clinical abnormalities vanished completely within 3 months after the elective abortion, which provided additional evidence that proteinuria and hypertension were caused purely by pregnancy. In general, the term preeclampsia refers to new onset of hypertension and proteinuria after 20 weeks of gestation. When proteinuria or hypertension is newly observed before 20 weeks of gestation, they are practically associated with triploidy, trophoblastic disease, or antiphospholipid syndrome. However, our case was not associated with them. Therefore, we called this case "pure" preeclampsia. We confirm the notion for the first time that preeclampsia associated with glomerular capillary endotheliosis can occur before 20 weeks of gestation. In addition, this report describes the earliest onset of preeclampsia compared with previously published reports. We also discuss causes of preeclampsia in early gestation and refer to the issue of the application of renal biopsies during pregnancy.

Phenotypic Characteristics Shared by Preeclamptic Patients and an Animal Model of the Syndrome: Report of a Pilot Study

Preeclampsia is a disorder that affects between 3% and 10% of all pregnancies. Progress in the understanding of the etiology (or etiologies) of this disorder has been impeded by the lack of suitable animal models of its early pathogenesis. Etiologic possibilities abound, and there are a number of considerations that suggest that preeclampsia is not one disease but rather a group of diseases with similar phenotypic characteristics. A rat model of this syndrome has been developed by inducing excessive volume expansion using desoxycorticosterone acetate and by replacing the drinking water with 0.9% saline. These animals develop hypertension, proteinuria, and intrauterine growth restriction (IUGR). However, they do not develop glomerular endotheliosis or a reduced glomerular filtration rate (GFR). We therefore surveyed the charts of patients with a discharge diagnosis of preeclampsia. We addressed the question of whether there was a group of such patients with the characteristics of our rat model. These include hypertension, proteinuria, IUGR, and either normal or only mildly abnormal GFR. We performed a retrospective chart review of 630 consecutive patients discharged with a diagnosis of preeclampsia. Of the patients, 1290 had all data available to allow appropriate analysis. A total of 29 patients demonstrated hypertension (>140/90 mm Hg), proteinuria (>300 mg/ 24 h), and IUGR and did not have any confounding comorbid conditions. Of these 29 patients, 18 had GFR that were within the range expected for gestational age or only slightly reduced. There is a group of patients that mirror the characteristics of our animal model. Accordingly, at least one etiology of preeclampsia is related to excessive expansion of the extracellular fluid volume.

Circulating levels of the antiangiogenic marker sFLT-1 are increased in first versus second pregnancies

Preeclampsia is far more common in women's first pregnancy but the mechanism of this association is unknown. Altered angiogenesis, marked by increased levels of circulating soluble fms-like tyrosine kinase (sFlt-1), an inhibitor of placental growth factor (PlGF) and vascular endothelial growth factor, has been implicated in the pathogenesis of preeclampsia. We tested the hypothesis that nulliparous women demonstrate increased sFlt-1 levels compared with multiparous women, suggesting an overall increase in relative antiangiogenesis during first pregnancies. We measured sFlt-1 and PlGF levels in early pregnancy serum samples from the first 2 completed pregnancies of 97 women who participated in the MOMS cohort study. Repeated measures analyses demonstrated that sFlt-1 levels were significantly increased in first compared with second pregnancies (877+/-598 pg/mL vs 728+/-399 pg/mL; P=.01) but there was no significant difference in PlGF levels (45.3+/-40.7 pg/mL vs 40.1+/-31.9 pg/mL; P=.14). After adjusting for age, gestational age, blood pressure, body mass index, smoking, and the interpregnancy time interval, the residual decrease in sFlt-1 levels from the first to the second pregnancy remained significant at 107 pg/mL (P=.04). Significant interaction between ethnicity and pregnancy order on sFlt-1 levels was observed such that Hispanic women demonstrated greater sFlt-1 levels than white women during their first pregnancy but lower levels in their second pregnancies. Increased sFlt-1 secretion in first versus second pregnancies may account in part for the increased risk of preeclampsia among nulliparous women. Additional studies are needed to verify these findings and to further examine ethnic differences in angiogenesis factors and their potential impact on the incidence of preeclampsia.

Steroid-Responsive Idiopathic Glomerular Capillary Endotheliosis: Case Report and Literature Review

Glomerular capillary endotheliosis is a lesion of endothelial cell injury. Morphological characteristics are endothelial swelling with glomerular hypertrophy and a reduction in capillary lumen size. This lesion commonly is found in patients with thrombotic microangiopathy, but similar histopathologic characteristics have been reported in patients with other diseases. A previously healthy 39-year-old woman presented with progressive lower-extremity swelling and arthralgias for 1 week. She had no other symptoms and denied prior illness. Her examination was remarkable for hypertension and pitting edema. Urine showed dysmorphic red blood cells and proteinuria. Serum creatinine level increased from 1.1 to 2.0 mg/dL (97 to 177 micromol/L) during several weeks. She did not meet criteria for systemic lupus erythematosus. Other test results included a negative pregnancy test and normal complement levels. Additional workup was negative for other causes of glomerular capillary endotheliosis. She underwent 2 renal biopsies. The first showed marked endothelial cell swelling, and the second biopsy 2 months later showed disease progression. Both were consistent with glomerular capillary endotheliosis. Proteinuria and serum creatinine level elevation responded to methylprednisolone therapy within 1 week, recurred after steroid doses were tapered, and responded again after restarting steroid therapy with monthly cyclophosphamide infusions. The differential diagnosis for glomerular capillary endotheliosis is limited. Various causes have been implicated, such as dysregulation of vascular endothelial growth factor, abnormal collagen production, and endothelial abnormalities. We did not identify prior cases of idiopathic glomerular capillary endotheliosis in the literature. Idiopathic glomerular capillary endotheliosis may be a newly recognized entity potentially responsive to steroid and cytotoxic regimens.

Glomerular endothelial cell differentiation

Glomerular endothelial cells differ from most other endothelial cells in that they are extraordinarily flattened and highly fenestrated. In this differentiated form, they allow formation of glomerular ultrafiltrate at a prodigious rate. Molecular processes that dictate the development and differentiation of glomerular endothelium are reviewed. During glomerular development, angioblasts already present in the metanephric blastema well before any organized angiogenic sprouts invade the capillary cleft of developing nephrons at the comma and S-shape stages in response to chemotactic and guiding cues from primitive podocytes. The angioblasts then undergo homotypic aggregation into precapillary cords as yet devoid of a lumen. Lumen development then proceeds through the loss of superfluous endothelial cells by apoptosis as well as flattening of the remaining viable endothelial cells. The final step, fenestration, is critically dependent on appropriate stimuli, most notably vascular endothelial growth factor A (VEGF-A), from differentiated podocytes. Current evidence suggests that the fenestrae of fully differentiated glomerular endothelium can be lost within hours if the VEGF-A stimulus is removed, and that the glomerular endotheliosis, loss of glomerular filtration rate (GFR) and proteinuria observed in preeclampsia are due to the circulating inhibitor of VEGF-A, soluble VEGF receptor 1 (VEGFR-1). Differentiation of the glomerular endothelium is highly dependent on podocyte-derived stimuli and their loss leads to the derangements of glomerular function in preeclampsia.

Human correlates of a rat model of preeclampsia

Preeclampsia is a disorder which affects between 3 and 10% of all pregnancies. It is the second leading cause of fetal wastage and maternal morbidity and mortality. It is characterized by hypertension, proteinuria and, often, excessive edema as well as intrauterine growth restriction (IUGR). Progress in the understanding of the etiology (etiologies) of this disorder has been impeded by the lack of suitable animal models of the early events in its pathogenesis. We have developed a rat model of this syndrome by inducing excessive volume expansion utilizing the administration of desoxycorticosterone acetate (DOCA) and replacing the drinking water of pregnant animals with 0.9% saline. As reported elsewhere, these animals develop hypertension, proteinuria and IUGR. They do not develop glomerular endotheliosis, hematologic or hepatic sequelae, reduced glomerular filtration rate (GFR) or eclampsia. To determine if there is a group of preeclamptic patients who have the same phenotypic characteristics as our animals, we performed a retrospective search of 100 charts of patients discharged with a diagnosis of preeclampsia. Thirty-two of these patients had all of the data available to allow us to draw conclusions. We considered IUGR to be present if birth weight was below the 10th percentile for gestational age. We found 15 of these 32 patients who demonstrated hypertension (>140/80), proteinuria(> 300 mg /24 hours) and IUGR. Seven of these 15 patients had GFRs that were within the range expected for their gestational age. We conclude that there is a group of human patients whose characteristics mirror those of our animal model. Accordingly, there is a human counterpart of this rodent model of preeclampsia that is related to excessive expansion of the extracellular fluid volume.

Gerard W. Ostheimer “What’s New in Obstetric Anesthesia” Lecture

Gerard W. Ostheimer “What’s New in Obstetric Anesthesia” Lecture

Introduction new developments in preeclampsia

Introduction new developments in preeclampsia

Introduction new developments in preeclampsia

Introduction new developments in preeclampsia

The role of VEGF-A in glomerular development and function.

Vascular endothelial growth factor is a major regulator of blood vessel biology and is highly expressed in presumptive and mature podocytes within the glomerulus. It has long been recognized that dysregulation of this factor occurs in a number of glomerular diseases; however, definitive proof that it plays a pathogenic or developmental role in glomerular biology has remained elusive. This review will summarize some of the recent advances in our understanding of the role(s) of VEGF in these processes. Gene targeting in the mouse has shown that tight regulation of vascular endothelial growth factor is required for development and maintenance of the glomerular filtration barrier. Podocyte-specific deletion of both alleles leads to congenital nephropathy and perinatal lethality. The glomeruli of mice that lack the 164 and 184 isoforms but express the 120 isoform, are smaller and have fewer capillary loops, whereas mice with podocyte-specific haploinsufficiency for all isoforms develop glomerular endotheliosis, the renal lesion seen in preeclampsia. Elevated levels of the soluble vascular endothelial growth factor receptor 1, which binds and inhibits circulating forms of VEGF were identified in patients with preeclampsia; rats injected with this soluble receptor develop hypertension, endotheliosis and proteinuria, similar to the lesion seen in podocyte-specific haploinsufficient VEGF mice. Conversely, podocyte-specific overexpression of the 164 isoform leads to collapsing glomerulopathy, the classic lesion seen in HIV-associated nephropathy. These results demonstrate that vascular endothelial growth factor plays a critical role in glomerular development and function, and provides the foundation to develop novel diagnostic or therapeutic tools for patients with glomerular disease.

Glomerular endotheliosis in normal pregnancy and pre-eclampsia

Objective To investigate the proportion of women with findings characteristic for pre-eclampsia, as opposed to renal disease, in a controlled study of hypertensive pregnant women undergoing antepartum renal biopsy. Design An observational prospective controlled study. Setting University Hospital of Lund, Sweden. Sample Thirty-six previously healthy women with hypertensive disease in pregnancy, consecutively admitted to the antenatal ward at onset of disease during a 20 month period and giving informed consent, as well as 12 voluntary healthy pregnant controls. Methods Renal biopsy samples were obtained from all participants and evaluated by light microscopy, electron microscopy and immunofluorescence techniques. Main outcome measures Presence and degree of glomerular endotheliosis. Results Glomerular endotheliosis was present in all women with pre-eclampsia and gestational hypertension, and in 5 of the 12 controls, although significant differences in the degree of endotheliosis were found between the groups. Clinically undetected renal disease was not diagnosed in any of the women. Conclusion Glomerular endotheliosis was found in women with normal pregnancy as well as in both non-proteinuric and proteinuric hypertension and is consequently not, as earlier believed, pathognomonic for pre-eclampsia. The transition between normal term pregnancy, gestational hypertension and pre-eclampsia appears to be a continuous process, perhaps of increasing adaptation to pregnancy. Pre-eclampsia may be the extreme of the adaptational process, rather than a separate abnormal condition. Clinically undetected renal disease could be a rare cause of hypertension in pregnancy.

Glomerular endotheliosis in normal pregnancy and pre‐eclampsia

To investigate the proportion of women with findings characteristic for pre-eclampsia, as opposed to renal disease, in a controlled study of hypertensive pregnant women undergoing antepartum renal biopsy. An observational prospective controlled study. University Hospital of Lund, Sweden. Thirty-six previously healthy women with hypertensive disease in pregnancy, consecutively admitted to the antenatal ward at onset of disease during a 20 month period and giving informed consent, as well as 12 voluntary healthy pregnant controls. Renal biopsy samples were obtained from all participants and evaluated by light microscopy, electron microscopy and immunofluorescence techniques. Presence and degree of glomerular endotheliosis. Glomerular endotheliosis was present in all women with pre-eclampsia and gestational hypertension, and in 5 of the 12 controls, although significant differences in the degree of endotheliosis were found between the groups. Clinically undetected renal disease was not diagnosed in any of the women. Glomerular endotheliosis was found in women with normal pregnancy as well as in both non-proteinuric and proteinuric hypertension and is consequently not, as earlier believed, pathognomonic for pre-eclampsia. The transition between normal term pregnancy, gestational hypertension and pre-eclampsia appears to be a continuous process, perhaps of increasing adaptation to pregnancy. Pre-eclampsia may be the extreme of the adaptational process, rather than a separate abnormal condition. Clinically undetected renal disease could be a rare cause of hypertension in pregnancy.