Evidence map›Paper›PMID 25941343›Full record

ArticleHypertension (Dallas, Tex. : 1979)2015

Classical Complement Pathway Activation in the Kidneys of Women With Preeclampsia.

Marlies Penning, Jamie S Chua, Cees van Kooten, Malu Zandbergen, Aletta Buurma, Joke Schutte, Jan Anthonie Bruijn, Eliyahu V Khankin, Kitty Bloemenkamp, S Ananth Karumanchi and 1 more

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
6.0field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 63 citations in OpenAlex.

  1. Alteration in tissue electrolyte and water balance in pregnant mice: the importance of potassium.Hypertension research : official journal of the Japanese Society of Hypertension · 2026
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  6. Inhibiting B cell activating factor attenuates preeclamptic symptoms in placental ischemic rats.American journal of reproductive immunology (New York, N.Y. : 1989) · 2023
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  15. Review
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  18. Serum Levels of Complement Factors C1q, Bb, and H in Normal Pregnancy and Severe Pre-Eclampsia.Medical science monitor : international medical journal of experimental and clinical research · 2019
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Marlies PenningFrom the Department of Pathology (M.P., J.S.C., M.Z., A.B., J.A.B., H.B.), Department of Nephrology (C.v.K.), and Department of Obstetrics (K.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Obstetrics & Gynecology, Isala Zwolle, Zwolle, the Netherlands (J.S.); and Howard Hughes Medical Institute and Department of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (E.V.K., S.A.K.).
Jamie S ChuaFrom the Department of Pathology (M.P., J.S.C., M.Z., A.B., J.A.B., H.B.), Department of Nephrology (C.v.K.), and Department of Obstetrics (K.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Obstetrics & Gynecology, Isala Zwolle, Zwolle, the Netherlands (J.S.); and Howard Hughes Medical Institute and Department of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (E.V.K., S.A.K.). j.s.chua@lumc.nl.
Cees van KootenFrom the Department of Pathology (M.P., J.S.C., M.Z., A.B., J.A.B., H.B.), Department of Nephrology (C.v.K.), and Department of Obstetrics (K.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Obstetrics & Gynecology, Isala Zwolle, Zwolle, the Netherlands (J.S.); and Howard Hughes Medical Institute and Department of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (E.V.K., S.A.K.).
Malu ZandbergenFrom the Department of Pathology (M.P., J.S.C., M.Z., A.B., J.A.B., H.B.), Department of Nephrology (C.v.K.), and Department of Obstetrics (K.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Obstetrics & Gynecology, Isala Zwolle, Zwolle, the Netherlands (J.S.); and Howard Hughes Medical Institute and Department of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (E.V.K., S.A.K.).
Aletta BuurmaFrom the Department of Pathology (M.P., J.S.C., M.Z., A.B., J.A.B., H.B.), Department of Nephrology (C.v.K.), and Department of Obstetrics (K.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Obstetrics & Gynecology, Isala Zwolle, Zwolle, the Netherlands (J.S.); and Howard Hughes Medical Institute and Department of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (E.V.K., S.A.K.).
Joke SchutteFrom the Department of Pathology (M.P., J.S.C., M.Z., A.B., J.A.B., H.B.), Department of Nephrology (C.v.K.), and Department of Obstetrics (K.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Obstetrics & Gynecology, Isala Zwolle, Zwolle, the Netherlands (J.S.); and Howard Hughes Medical Institute and Department of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (E.V.K., S.A.K.).
Jan Anthonie BruijnFrom the Department of Pathology (M.P., J.S.C., M.Z., A.B., J.A.B., H.B.), Department of Nephrology (C.v.K.), and Department of Obstetrics (K.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Obstetrics & Gynecology, Isala Zwolle, Zwolle, the Netherlands (J.S.); and Howard Hughes Medical Institute and Department of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (E.V.K., S.A.K.).
Eliyahu V KhankinFrom the Department of Pathology (M.P., J.S.C., M.Z., A.B., J.A.B., H.B.), Department of Nephrology (C.v.K.), and Department of Obstetrics (K.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Obstetrics & Gynecology, Isala Zwolle, Zwolle, the Netherlands (J.S.); and Howard Hughes Medical Institute and Department of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (E.V.K., S.A.K.).
Kitty BloemenkampFrom the Department of Pathology (M.P., J.S.C., M.Z., A.B., J.A.B., H.B.), Department of Nephrology (C.v.K.), and Department of Obstetrics (K.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Obstetrics & Gynecology, Isala Zwolle, Zwolle, the Netherlands (J.S.); and Howard Hughes Medical Institute and Department of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (E.V.K., S.A.K.).
S Ananth KarumanchiFrom the Department of Pathology (M.P., J.S.C., M.Z., A.B., J.A.B., H.B.), Department of Nephrology (C.v.K.), and Department of Obstetrics (K.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Obstetrics & Gynecology, Isala Zwolle, Zwolle, the Netherlands (J.S.); and Howard Hughes Medical Institute and Department of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (E.V.K., S.A.K.).
Hans BaeldeFrom the Department of Pathology (M.P., J.S.C., M.Z., A.B., J.A.B., H.B.), Department of Nephrology (C.v.K.), and Department of Obstetrics (K.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Obstetrics & Gynecology, Isala Zwolle, Zwolle, the Netherlands (J.S.); and Howard Hughes Medical Institute and Department of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA (E.V.K., S.A.K.).
Leiden University Medical Center · NLIsala · NL

Funding

Preeclampsia and renal complications: late effects on kidney and vasculatureK08DK101560 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KHANKIN, ELIYAHU · 2014 to 2017
$616k
Howard Hughes Medical InstituteNIDDK NIH HHS K08 DK101560
6 · The paper itself

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.

Indexed as

Complement Pathway, ClassicalAdultAnimalsBiomarkersChronic DiseaseComplement C4bComplement Factor DComplement System ProteinsDisease Models, AnimalFemaleHumansHypertensionImmunoglobulinsKidney GlomerulusMannose-Binding LectinsMiceBiomarkersComplement C4bcomplement C4dComplement Factor Dcomplement factor D, mouseComplement System ProteinsFlt1 protein, mouseImmunoglobulinsMannose-Binding LectinsPeptide FragmentsVascular Endothelial Growth Factor Receptor-1C4dcomplementhypertension kidneypreeclampsiaproteinuriasFlt-1

Identifiers

PMID25941343
PMCPMC4465860
OpenAlexW2107839246

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.