Advances in the pathophysiology of pre-eclampsia and related podocyte injury (original) (raw)
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Podocytes—The Most Vulnerable Renal Cells in Preeclampsia
International Journal of Molecular Sciences
Preeclampsia (PE) is a disorder that affects 3–5% of normal pregnancies. It was believed for a long time that the kidney, similarly to all vessels in the whole system, only sustained endothelial damage. The current knowledge gives rise to a presumption that the main role in the development of proteinuria is played by damage to the podocytes and their slit diaphragm. The podocyte damage mechanism in preeclampsia is connected to free VEGF and nitric oxide (NO) deficiency, and an increased concentration of endothelin-1 and oxidative stress. From national cohort studies, we know that women who had preeclampsia in at least one pregnancy carried five times the risk of developing end-stage renal disease (ESRD) when compared to women with physiological pregnancies. The focal segmental glomerulosclerosis (FSGS) is the dominant histopathological lesion in women with a history of PE. The kidney’s podocytes are not subject to replacement or proliferation. Podocyte depletion exceeding 20% result...
Persistent Urinary Podocyte Loss following Preeclampsia May Reflect Subclinical Renal Injury
PLoS ONE, 2014
Objective: Studies have shown that podocyturia, i.e., urinary loss of viable podocytes (glomerular epithelial cells), is associated with proteinuria in preeclampsia. We postulated that urinary podocyte loss may persist after preeclamptic pregnancies, thus resulting in renal injury. This may lead to future chronic renal injury. In addition, we compared the postpartum levels of the angiogenic factors, which previously have been associated with preeclampsia, between normotensive versus preeclamptic pregnancies.
Urinary podocyte excretion as a marker for preeclampsia
American Journal of Obstetrics and Gynecology, 2007
The objective of this study was to examine whether podocyturia, which is the urinary excretion of viable podocytes (glomerular epithelial cells), is present in urinary sediments of patients with preeclampsia. We also aimed to compare the test characteristics of podocyturia to those angiogenic factors that have been shown to play an important role in the pathogenesis of preeclampsia (s-Flt-1, PlGF, and endoglin).
Gynecology & Obstetrics, 2015
Objectives: We sought to optimise and validate an L-nitroarginine methyl ester (L NAME) pre-eclamptic model with a focus on the role of serum and renal angiogenic and antiangiogenic factors on urinary podocyte mRNA excretion. Study design: 120 nulliparous female Sprague-Dawley rats were divided into 5 groups (n=24 in each group). A pregnant control, two groups that represented early and late-onset PE (pre-eclampsia) and two groups that were treated with Sildenafil Citrate (SC) to show remission of the pre-eclamptic-like symptoms, were used. Results: The early-onset PE group (1.31 ± 0.02) and the late-onset PE group (1.12 ± 0.01) showed a significant increase in urinary levels of nephrin mRNA, when compared to the pregnant control group (0.75 ± 0.02) on day 19 (p<0.01). There was also a significant increase in urinary levels of podocin mRNA on day 19, the early-onset PE group (1.53 ± 0.03) and late-onset PE group (1.38 ± 0.07) when compared to the pregnant control group (0.96 ± 0.04), respectively (p<0.01). Similar significant increases were seen with regards to serum levels and renal expression of sFlt-1, while there were significant decreases in renal VEGF expression and serum PlGF levels in the PE groups. The sildenafil citrate treated animals did not display these symptoms, showing that its vasodilatory effects may protect against the development of the pre-eclamptic-like syndrome. Conclusion: The L-NAME model of PE is an ideal model to study PE, since it mimics the pathogenesis of the disorder. It also highlights the importance of future research into the use of podocyturia as a potential biomarker for PE.
Association of preeclampsia with podocyte turnover
Clinical journal of the American Society of Nephrology : CJASN, 2014
Preeclampsia is characterized by hypertension and proteinuria, and increased shedding of podocytes into the urine is a common finding. This finding raises the question of whether preeclamptic nephropathy involves podocyte damage. This study examined podocyte-related changes in a unique sample of renal tissues obtained from women who died of preeclampsia. All patients with preeclampsia who died in The Netherlands since 1990 and had available autopsy tissue were identified using a nationwide database of the Dutch Pathology Registry (PALGA). This resulted in a cohort of 11 women who died from preeclampsia. Three control groups were also identified during the same time period, and consisted of normotensive women who died during pregnancy (n=25), and nonpregnant controls either with (n=14) or without (n=13) chronic hypertension. Glomerular lesions, including podocyte numbers, podocyte proliferation, and parietal cell activation, were measured. Patients with preeclampsia had prominent cha...
Nephrology Dialysis Transplantation, 2007
Background. Preeclampsia is a pregnancy-specific disorder characterized by hypertension and proteinuria. In other disease states, proteinuria has been linked to altered expressions of podocyte foot-process proteins, but this has not been studied in women with preeclampsia. We sought to test the hypothesis that proteinuria in preeclampsia is associated with dysregulated expression of the podocyte cytoskeleton and/or tight junction proteins. Mathods. Renal tissue was obtained from autopsy material from seven women who had severe preeclampsia during the second half of their pregnancies up to 48 h after delivery, and who subsequently died. As controls, we used autopsy material from two women who died accidentally during the second half of their otherwise normal pregnancies. Immunohistochemical stains for nephrin, synaptopodin and podocin were performed on representative sections prepared from paraffin-embedded material.
Urinary Extracellular Vesicles of Podocyte Origin and Renal Injury in Preeclampsia
Journal of the American Society of Nephrology : JASN, 2017
Renal histologic expression of the podocyte-specific protein, nephrin, but not podocin, is reduced in preeclamptic compared with normotensive pregnancies. We hypothesized that renal expression of podocyte-specific proteins would be reflected in urinary extracellular vesicles (EVs) of podocyte origin and accompanied by increased urinary soluble nephrin levels (nephrinuria) in preeclampsia. We further postulated that podocyte injury and attendant formation of EVs are related mechanistically to cellfree fetal hemoglobin (HbF) in maternal plasma. Our study population included preeclamptic (n=49) and normotensive (n=42) pregnant women recruited at delivery. Plasma measurements included HbF concentrations and concentrations of the endogenous chelators haptoglobin, hemopexin, and α1- microglobulin. We assessed concentrations of urinary EVs containing immunologically detectable podocyte-specific proteins by digital flow cytometry and measured nephrinuria by ELISA. The mechanistic role of Hb...
PloS one, 2014
Preeclampsia, a hypertensive multisystem disease that complicates 5-8% of all pregnancy, is a major cause for maternal and fetal mortality and morbidity. The disease is associated with increased spontaneous and evoked preterm birth and remote cardio-renal disorders in the mother and offspring. Thus the ability to predict the disease should lead to earlier care and decreased morbidity. This has led to fervent attempts to identify early predictive biomarkers and research endeavors that have expanded as we learn more regarding possible causes of the disease. As preeclampsia is associated with specific renal pathology including podocyte injury, early urinary podocyte (podocyturia), or the podocyte specific proteinuria nephrin in the urine (nephrinuria), as well as the more easily measured urinary albumin (albuminuria), have all been suggested as predictive markers. We performed a prospective study recruiting 91 pregnant women (78 of whom were high risk) and studied the predictive abilit...