S Ananth Karumanchi

Howard Hughes Medical Institute, Ашбърн, Virginia, United States

Are you S Ananth Karumanchi?

Claim your profile

Publications (251)1762.47 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: -The pathophysiology of hypertension in the immediate postpartum period is unclear. Methods and results: -We studied 988 consecutive women admitted to a tertiary medical center for cesarean section of a singleton pregnancy. Angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF), both biomarkers associated with preeclampsia, were measured on antepartum blood samples. We then performed multivariable analyses to determine factors associated with the risk of developing postpartum hypertension. Of the 988 women, 184 women (18.6%) developed postpartum hypertension. 77 out of 184 women developed de novo hypertension in the postpartum period and the remainder had a hypertensive disorder of pregnancy in the antepartum period. A higher body mass index and history of diabetes mellitus were associated with development of postpartum hypertension. The antepartum sFlt1/PlGF ratio positively correlated with blood pressures in the postpartum period [highest postpartum systolic (r=0.29; P<0.001) and diastolic (r=0.28, P<0.001)]. Moreover, the highest tertile of the antepartum sFlt1/PlGF ratio was independently associated with postpartum hypertension [OR: 2.25 (1.19, 4.25), P=0.01 in the de novo hypertensive group and 2.61 (1.12, 6.05) in the persistent hypertensive group; P=0.02] in multivariable analysis. Women developing postpartum hypertension had longer hospitalization than those who remained normotensive (6.5 ± 3.5 versus 5.7 ± 3.4 days; P<0.001). Conclusions: -Hypertension in the postpartum period is relatively common and is associated with prolonged hospitalization. Women with postpartum hypertension share similar clinical risk factors as well as a similar antepartum plasma angiogenic profile found in women with preeclampsia. These data suggest that postpartum hypertension may represent a group of women with subclinical or unresolved preeclampsia.
    Circulation 09/2015; DOI:10.1161/CIRCULATIONAHA.115.015721 · 14.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Maternal cigarette smoking during pregnancy remains one of the most common and preventable causes of fetal growth restriction (FGR), a condition in which a fetus is unable to achieve its genetically determined potential size. Even though epidemiologic evidence clearly links maternal cigarette smoking with FGR, insight into the molecular mechanisms of cigarette smoke-induced FGR is lacking. Here, we performed transcriptional profiling of placentas obtained from smoking mothers who delivered growth-restricted infants and identified secreted frizzled-related protein 1 (sFRP1), an extracellular antagonist of endogenous WNT signaling, as a candidate molecule. sFRP1 mRNA and protein levels were markedly upregulated (~10 fold) in placentas from smoking mothers compared with those from nonsmokers. In pregnant mice, adenovirus-mediated overexpression of sFRP1 led to FGR, increased karyorrhexis in the junctional zone, and decreased proliferation of labyrinthine trophoblasts. Consistent with our hypothesis that placental WNT signaling is suppressed in maternal smokers, we found that exposure to carbon monoxide analogs led to reduced WNT signaling, increased SFRP1 mRNA expression, and decreased cellular proliferation in a trophoblast cell line. Moreover, administration of carbon monoxide analogs to pregnant mice in late gestation led to FGR. In summary, our results indicate that the increased placental expression of sFRP1 seen in smokers impairs fetal growth by inhibiting WNT signaling and trophoblast proliferation.
    The Journal of clinical investigation 09/2015; DOI:10.1172/JCI80457 · 13.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Preeclampsia is a devastating complication of pregnancy. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic protein believed to mediate the signs and symptoms of preeclampsia. We conducted an open pilot study to evaluate the safety and potential efficacy of therapeutic apheresis with a plasma-specific dextran sulfate column to remove circulating sFlt-1 in 11 pregnant women (20-38 years of age) with very preterm preeclampsia (23-32 weeks of gestation, systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, new onset protein/creatinine ratio >0.30 g/g, and sFlt-1/placental growth factor ratio >85). We evaluated the extent of sFlt-1 removal, proteinuria reduction, pregnancy continuation, and neonatal and fetal safety of apheresis after one (n=6), two (n=4), or three (n=1) apheresis treatments. Mean sFlt-1 levels were reduced by 18% (range 7%-28%) with concomitant reductions of 44% in protein/creatinine ratios. Pregnancy continued for 8 days (range 2-11) and 15 days (range 11-21) in women treated once and multiple times, respectively, compared with 3 days (range 0-14) in untreated contemporaneous preeclampsia controls (n=22). Transient maternal BP reduction during apheresis was managed by withholding pre-apheresis antihypertensive therapy, saline prehydration, and reducing blood flow through the apheresis column. Compared with infants born prematurely to untreated women with and without preeclampsia (n=22 per group), no adverse effects of apheresis were observed. In conclusion, therapeutic apheresis reduced circulating sFlt-1 and proteinuria in women with very preterm preeclampsia and appeared to prolong pregnancy without major adverse maternal or fetal consequences. A controlled trial is warranted to confirm these findings.
    Journal of the American Society of Nephrology 09/2015; DOI:10.1681/ASN.2015020157 · 9.34 Impact Factor
  • Christina W Chen · S Ananth Karumanchi ·

    American Journal of Nephrology 09/2015; 42(2):115-116. DOI:10.1159/000439189 · 2.67 Impact Factor

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Over 20% of pregnancies in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibodies (APL) result in an adverse pregnancy outcome (APO) related to abnormal placentation. The ability to identify, early in pregnancy, patients who are destined for poor outcomes would significantly impact care of this high risk population. In non-autoimmune patients, circulating angiogenic factors are dysregulated in disorders of placentation, such as preeclampsia (PE) and fetal growth restriction. Objective: To determine whether early dysregulation of circulating angiogenic factors, can predict APO in high risk SLE and/or APL pregnancies. Study design: We used data and samples from the PROMISSE Study (Predictors of pRegnancy Outcome: BioMarkers In antiphospholipid antibody Syndrome and Systemic Lupus Erythematosus), a multi-center prospective study that enrolled 492 pregnant women with SLE and/or APL between September 2003 and August 2013. Patients were followed through pregnancy from <12 weeks gestation. Circulating levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF) and soluble endoglin (sEng) were measured monthly and subjects followed for APO, classified as severe (PE<34 weeks, fetal/neonatal death, indicated pre-term delivery <30 weeks) or moderate (PE≥34 weeks, indicated preterm delivery 30-36 weeks, growth restriction without PE). Results: Severe APOs occurred in 12% and moderate APOs in 10% of patients. By 12-15 weeks, sFlt1, PlGF, and sEng levels were markedly altered in women who developed severe APO. After adjusting for clinical risk factors, sFlt1 was the strongest predictor of severe APO among 12-15 week measures (odds ratio=17.3 comparing highest and lowest quartiles, 95% CI: 3.5-84.8; positive predictive value (PPV)=61%; negative predictive value (NPV)=93%). At 16-19 weeks, the combination of sFlt1 and PlGF was most predictive of severe APO, with risk greatest for subjects with both PlGF in lowest quartile (<70.3 pg/ml) and sFlt1 in highest quartile (>1872 pg/ml; odds ratio=31.1; 95% CI: 8.0-121.9; PPV=58%; NPV=95%). Severe APO rate in this high risk subgroup was 94% (95%CI: 70%-99.8%), if lupus anticoagulant or history of high blood pressure is additionally present. In contrast, among patients with both sFlt1 <1872 pg/ml and PlGF >70.3 pg/ml, rate of severe APO was only 4.6% (95% CI: 2.1%- 8.6%). Conclusions: Circulating angiogenic factors measured during early gestation have a high negative predictive value in ruling out the development of severe adverse outcomes among patients with SLE and/or APL syndrome. Timely risk stratification of patients is important for effective clinical care and optimal allocation of healthcare resources.
    American journal of obstetrics and gynecology 09/2015; DOI:10.1016/j.ajog.2015.09.066 · 4.70 Impact Factor
  • Tammy Hod · Ana Sofia Cerdeira · S Ananth Karumanchi ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Preeclampsia is a pregnancy-specific disease characterized by new onset hypertension and proteinuria after 20 wk of gestation. It is a leading cause of maternal and fetal morbidity and mortality worldwide. Exciting discoveries in the last decade have contributed to a better understanding of the molecular basis of this disease. Epidemiological, experimental, and therapeutic studies from several laboratories have provided compelling evidence that an antiangiogenic state owing to alterations in circulating angiogenic factors leads to preeclampsia. In this review, we highlight the role of key circulating antiangiogenic factors as pathogenic biomarkers and in the development of novel therapies for preeclampsia. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
    Cold Spring Harbor Perspectives in Medicine 08/2015; 5(10). DOI:10.1101/cshperspect.a023473 · 9.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background/Aims. Acute kidney injury is a common problem for patients with cirrhosis and is associated with poor survival. We aimed to examine the association between type of acute kidney injury and 90-day mortality. Methods. Prospective cohort study at a major US liver transplant center. A nephrologist's review of the urinary sediment was used in conjunction with the 2007 Ascites Club Criteria to stratify acute kidney injury into four groups: prerenal azotemia, hepatorenal syndrome, acute tubular necrosis, or other. Results. 120 participants with cirrhosis and acute kidney injury were analyzed. Ninety-day mortality was 14/40 (35%) with prerenal azotemia, 20/35 (57%) with hepatorenal syndrome, 21/36 (58%) with acute tubular necrosis, and 1/9 (11%) with other (p = 0.04 overall). Mortality was the same in hepatorenal syndrome compared to acute tubular necrosis (p = 0.99). Mortality was lower in prerenal azotemia compared to hepatorenal syndrome (p = 0.05) and acute tubular necrosis (p = 0.04). Ten participants (22%) were reclassified from hepatorenal syndrome to acute tubular necrosis because of granular casts on urinary sediment. Conclusions. Hepatorenal syndrome and acute tubular necrosis result in similar 90-day mortality. Review of urinary sediment may add important diagnostic information to this population. Multicenter studies are needed to validate these findings and better guide management.
    International Journal of Nephrology 08/2015; 2015(1):108139. DOI:10.1155/2015/108139
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thrombotic microangiopathy (TMA) is a life-threatening condition that affects some, but not all, recipients of vascular endothelial growth factor (VEGF) inhibitors given as part of chemotherapy. TMA is also a complication of preeclampsia, a disease characterized by excess production of the VEGF-scavenging soluble VEGF receptor 1 (soluble fms-like tyrosine kinase 1; sFlt-1). Risk factors for VEGF inhibitor-related TMA remain unknown. We hypothesized that deficiency of the VWF-cleaving ADAMTS13 endopeptidase contributes to the development of VEGF inhibitor-related TMA. ADAMTS13(-/-) mice overexpressing sFlt-1 presented all hallmarks of TMA, including thrombocytopenia, schistocytosis, anemia, and VWF-positive microthrombi in multiple organs. Similar to VEGF inhibitor-related TMA in humans, these mice exhibited severely impaired kidney function and hypertension. In contrast, wild-type mice overexpressing sFlt-1 developed modest hypertension but no other features of TMA. Recombinant ADAMTS13 therapy ameliorated all symptoms of TMA in ADAMTS13(-/-) mice overexpressing sFlt-1 and normalized BP in wild-type mice. ADAMTS13 activity may thus be a critical determinant for the development of TMA secondary to VEGF inhibition. Administration of recombinant ADAMTS13 may serve as a therapeutic approach to treat or prevent thrombotic complications of VEGF inhibition. Copyright © 2015 by the American Society of Nephrology.
    Journal of the American Society of Nephrology 06/2015; DOI:10.1681/ASN.2014121165 · 9.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Angiogenic factors are strongly associated with adverse maternal and fetal outcomes among women with preterm preeclampsia (PE) in developed countries. We evaluated the role of angiogenic factors and their relationship to adverse outcomes among Haitian women with PE. Material and methods: We measured plasma antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) levels in women with PE (n=35) compared to controls with no hypertensive disorders (NHD) (n=43) among subjects with singleton pregnancies that delivered at Hospital Albert Schweitzer (HAS) in Haiti. We divided the preeclamptic women into two groups, early onset (≤ 34 weeks) and late onset (>34 weeks) and examined relationships between sFlt1/PlGF ratios on admission and adverse outcomes (abruption, respiratory complications, stroke, renal insufficiency, eclampsia, maternal death, birth weight <2500 grams, or fetal/neonatal death) in women with PE subgroups as compared to NHD groups separated by week of admission. Data are presented as median (25th-75th centile), n (%), and proportions. Results: Among patients with PE, most (24/35) were admitted at term. Adverse outcome rates in PE were much higher among the early onset group compared to the late onset group (100.0% vs. 54.2%, P=0.007). Plasma angiogenic factors were dramatically altered in both subtypes of PE. Angiogenic factors also correlated with adverse outcomes in both subtypes of PE. The median sFlt1/PlGF ratios for subjects with early onset PE with any adverse outcome vs. NHD <=34 weeks with no adverse outcome were 703.1 (146.6, 1614.9) and 9.6 (3.5, 58.6); P<0.001). Among late onset group the median sFlt1/PlGF ratio for women with any adverse outcome was 130.7 (56.1, 242.6) versus 22.4 (10.2, 58.7; P=0.005) in NHD >34 weeks with no adverse outcome. Conclusion: PE-related adverse outcomes are common in women in Haiti and are associated with profound angiogenic imbalance regardless of gestational age at presentation.
    PLoS ONE 05/2015; 10(5):e0126815. DOI:10.1371/journal.pone.0126815 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A growing body of evidence suggests that complement dysregulation plays a role in the pathogenesis of preeclampsia. The kidney is one of the major organs affected in preeclampsia. Because the kidney is highly susceptible to complement activation, we hypothesized that preeclampsia is associated with renal complement activation. We performed a nationwide search for renal autopsy material in the Netherlands using a computerized database (PALGA). Renal tissue was obtained from 11 women with preeclampsia, 25 pregnant controls, and 14 nonpregnant controls with hypertension. The samples were immunostained for C4d, C1q, mannose-binding lectin, properdin, C3d, C5b-9, IgA, IgG, and IgM. Preeclampsia was significantly associated with renal C4d-a stable marker of complement activation-and the classical pathway marker C1q. In addition, the prevalence of IgM was significantly higher in the kidneys of the preeclamptic women. No other complement markers studied differed between the groups. Our findings in human samples were validated using a soluble fms-like tyrosine kinase 1 mouse model of preeclampsia. The kidneys in the soluble fms-like tyrosine kinase 1-injected mice had significantly more C4 deposits than the control mice. The association between preeclampsia and renal C4d, C1q, and IgM levels suggests that the classical complement pathway is involved in the renal injury in preeclampsia. Moreover, our finding that soluble fms-like tyrosine kinase 1-injected mice develop excess C4 deposits indicates that angiogenic dysregulation may play a role in complement activation within the kidney. We suggest that inhibiting complement activation may be beneficial for preventing the renal manifestations of preeclampsia. © 2015 American Heart Association, Inc.
    Hypertension 05/2015; 66(1). DOI:10.1161/HYPERTENSIONAHA.115.05484 · 6.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 24,25-Dihydroxyvitamin D [24,25(OH)2D] is a metabolite of 25-hydroxyvitamin D (25D). Blacks frequently have low total 25D without manifestations of vitamin D deficiency, suggesting that total serum 25D may incorrectly reflect vitamin D status in different racial groups. The ratio of serum 24,25(OH)2D to 25D [vitamin D metabolite ratio (VMR)] represents a new candidate biomarker for vitamin D status. We measured 24,25(OH)2D3 and 25D3 by mass spectrometry in a random community cohort of black (n = 212) and white (n = 164) Americans to evaluate VMR as a marker for vitamin D status. We measured parathyroid hormone concentrations by immunoassay to compare VMR and 25D3 against a physiological indicator of vitamin D deficiency. Serum 24,25(OH)2D3 strongly correlated with 25D3 in both black and white study participants (r = 0.90, P < 0.001 and r = 0.86, P < 0.001 respectively). Blacks had lower mean 25D3 than whites [17.0 (7.8) vs 27.5 (11.3) ng/mL; 42.4 (19.5) vs 68.6 (28.2) nmol/L, P < 0.001] and lower mean 24,25(OH)2D3 [2.1 (1.3) vs 3.6 (2.0) ng/mL; 5.1 (3.1) vs 8.7 (4.8) nmol/L, P < 0.001]. In contrast to total 25D3 concentrations, mean VMR values were similar in blacks and whites [11.9 (4.0) vs 12.5 (3.4), P = 0.16, respectively] and were negatively correlated with parathyroid hormone concentrations in both races (rs = -0.26, P < 0.001, and rs = -0.25, P < 0.001, respectively). Our results provide further evidence that measurement of total 25D for assessment of vitamin D status in patients of African descent deserves reevaluation and suggest that alternative measures such as VMR should be considered. © 2015 American Association for Clinical Chemistry.
    Clinical Chemistry 04/2015; 61(6). DOI:10.1373/clinchem.2015.240051 · 7.91 Impact Factor

  • Geburtshilfe und Frauenheilkunde 04/2015; 75(03). DOI:10.1055/s-0035-1548707 · 0.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Protein carbamylation is a urea-driven post-translational protein modification associated with mortality in dialysis patients. Free amino acids (AAs) are competitive inhibitors of protein carbamylation and animal studies suggest increasing AA concentrations reduces carbamylation burden. We hypothesized that AA therapy in maintenance hemodialysis patients would reduce carbamylation, carrying the potential to improve clinical outcomes. Prospective pilot clinical trial (NCT1612429). The study was conducted from March 2013 to March 2014 in outpatient dialysis facilities in the Boston metropolitan area. We enrolled 23 consecutively consenting hemodialysis subjects, infusing the first 12 individuals with 250 cc of AAs 3 times per week postdialysis over 8 weeks. The remaining 11 subjects served as controls. Change in carbamylated albumin (C-Alb), a measure of total body carbamylation burden, between baseline and 8 weeks was the primary outcome. The treated and control groups had similar clinical characteristics and similar baseline C-Alb levels (mean ± SE 9.5 ± 2.4 and 9.3 ± 1.3 mmol/mol, respectively; P = .61). The treated arm showed a significant reduction in C-Alb compared with controls at 4 weeks (8.4% reduction in the treated arm vs. 4.3% increase in controls; P = .03) and the effect was greater by 8 weeks (15% reduction in the treated vs. 1% decrease in controls; P = .01). In this pilot study, AA therapy appeared safe and effective at reducing C-Alb levels in hemodialysis patients compared with no treatment. The impact of reduced protein carbamylation on clinical outcomes should be further investigated. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    Journal of Renal Nutrition 03/2015; 25(4). DOI:10.1053/j.jrn.2015.01.019 · 1.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cardiovascular disease (CVD) remains the leading killer of women in developed nations. One sex-specific risk factor is preeclampsia, a syndrome of hypertension and proteinuria that complicates 5% of pregnancies. Although preeclampsia resolves after delivery, exposed women are at increased long-term risk of premature CVD and mortality. Pre-existing CVD risk factors are associated with increased risk of developing preeclampsia but whether preeclampsia merely uncovers risk or contributes directly to future CVD remains a critical unanswered question. A mouse preeclampsia model was used to test the hypothesis that preeclampsia causes an enhanced vascular response to future vessel injury. A preeclampsia-like state was induced in pregnant CD1 mice by overexpressing soluble fms-like tyrosine kinase-1, a circulating antiangiogenic protein that induces hypertension and glomerular disease resembling human preeclampsia. Two months postpartum, soluble fms-like tyrosine kinase-1 levels and blood pressure normalized and cardiac size and function by echocardiography and renal histology were indistinguishable in preeclampsia-exposed compared with control mice. Mice were then challenged with unilateral carotid injury. Preeclampsia-exposed mice had significantly enhanced vascular remodeling with increased vascular smooth muscle cell proliferation (180% increase; P<0.01) and vessel fibrosis (216% increase; P<0.001) compared with control pregnancy. In the contralateral uninjured vessel, there was no difference in remodeling after exposure to preeclampsia. These data support a new model in which vessels exposed to preeclampsia retain a persistently enhanced vascular response to injury despite resolution of preeclampsia after delivery. This new paradigm may contribute to the substantially increased risk of CVD in woman exposed to preeclampsia. © 2015 American Heart Association, Inc.
    Hypertension 02/2015; 65(4). DOI:10.1161/HYPERTENSIONAHA.114.04971 · 6.48 Impact Factor
  • Source
    Marco Scioscia · S Ananth Karumanchi · Debra Goldman-Wohl · Pierre-Yves Robillard ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Several clinical and basic science reports have elucidated partial aspects of the pathophysiology of preeclampsia and have led many authors to conclude that different "subtypes" of the disease exist. All these subtypes share the main clinical features of the disease and present additional characteristics that define different clinical phenotypes. Nevertheless, immunological alterations, endothelial dysfunction, and insulin resistance constantly characterize this syndrome. These aspects are intimately related at a molecular level; thus, we propose an alternative approach to explaining biologically the main intracellular processes that occur in preeclampsia and this may yield an insight into the pathogenesis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Journal of Reproductive Immunology 02/2015; 108. DOI:10.1016/j.jri.2015.01.009 · 2.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Serum carbamylated albumin (C-Alb) levels are associated with excess mortality in patients with diabetic end-stage renal disease. To gain insight into the pathophysiology of carbamylation, we determined associations between C-Alb and causes of death in patients on chronic hemodialysis. The Die Deutsche Diabetes Dialyse Studie (4D study) was a randomized controlled trial testing the effects of atorvastatin on survival in diabetic patients on dialysis during a median follow-up of 4 years. We stratified 1161 patients by C-Alb to see whether differences in carbamylation altered the effects of atorvastatin on survival. Baseline C-Alb significantly correlated with serum cardiac stress markers troponin T and N-terminal pro-B-type-natriuretic peptide and was associated with a history of heart failure and arrhythmia. C-Alb was strongly associated with 1-year adjusted risk of cardiovascular mortality, sudden cardiac death, and the 4-year risk of death from congestive heart failure (hazard ratios of 3.06, 3.78, and 4.64, respectively) but not with myocardial infarction or stroke. Patients with low C-Alb, treated with atorvastatin, experienced a significant improvement in their 4-year survival (hazard ratio 0.692). High C-Alb levels are associated with ongoing cardiac damage, risk of congestive heart failure, and sudden cardiac death. Thus, carbamylation and uremic cardiomyopathy are associated in patients with diabetes mellitus and kidney disease. In addition, statins were specifically beneficial to hemodialysis patients with low C-Alb.Kidney International advance online publication, 11 February 2015; doi:10.1038/ki.2014.429.
    Kidney International 02/2015; 87(6). DOI:10.1038/ki.2014.429 · 8.56 Impact Factor
  • Article: [24-OR]

  • [Show abstract] [Hide abstract]
    ABSTRACT: Assess the accuracy of serum soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and soluble endoglin (sEng) and urinary PlGF as predictors of preeclampsia in a prospective multicountry study. From 2006-9, 5121 pregnant women from centers in Argentina, Colombia, India, Italy, Kenya, Peru, Switzerland and Thailand had their serum tested for sFlt-1, PlGF and sEng levels and their urine for PlGF levels at ⩽20 (index tests, results kept blind from care givers), 23-27 and 32-35weeks' gestation. During prenatal care, women were closely monitored for signs of preeclampsia, diagnosed by systolic blood pressure ⩾140mmHg and/or diastolic blood pressure ⩾90mmHg, and proteinuria with protein/creatinine ratio ⩾0.3, protein ⩾1g/l or, one dipstick measurement ⩾2+ appearing after gestational week 20, and defined as early preeclampsia when these signs appeared before 34 weeks' gestation. Preeclampsia was diagnosed in 3.9% (198 of the 5121 women) whom 47 (0.9%) had early disease. No test performed well at <20 weeks for either early or all preeclampsia (area under receiver operating characteristics curve, AUC ⩽0.6). Multivariable models combining biomarkers with clinical features (age, body mass index, smoking, multiple pregnancy, hypertension or treatment for it) did not improve the prediction capability before 20weeks. Serum PlGF was the best predictor of preeclampsia at any gestation (AUC 0.82 at 32-35weeks) and at early onset (AUC 0.82 at 23-27weeks). Angiogenic biomarkers, alone or combined with clinical risk factors, performed poorly as predictors of preeclampsia, when measured early in pregnancy (<20weeks). M. Widmer: None. C.B. Cuesta: None. K. Khan: None. A.M. Gülmezoglu: None. S.A. Karumanchi: Consultant: Roche, Beckman, Siemens. M.D. Lindheimer: None. Copyright © 2014.
    01/2015; 5(1):50. DOI:10.1016/j.preghy.2014.10.097
  • Article: [27-OR]

Publication Stats

14k Citations
1,762.47 Total Impact Points


  • 2009-2015
    • Howard Hughes Medical Institute
      Ашбърн, Virginia, United States
  • 2007-2015
    • Harvard University
      Cambridge, Massachusetts, United States
    • Beckman Coulter Inc.
      Ontario, California, United States
  • 2001-2015
    • Beth Israel Deaconess Medical Center
      • • Center for Vascular Biology Research
      • • Department of Medicine
      • • Division of Nephrology
      Boston, Massachusetts, United States
  • 2012
    • Tufts University
      • Tufts Center for Conservation Medicine
      Бостон, Georgia, United States
  • 2006-2012
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2008
    • University of Chicago
      • Department of Obstetrics & Gynecology
      Chicago, Illinois, United States
  • 2004
    • Ewha Womans University
      Sŏul, Seoul, South Korea
    • Baylor College of Medicine
      • Department of Pediatrics
      Houston, Texas, United States
  • 2002
    • Albert Einstein College of Medicine
      New York, New York, United States