Evidence map›Paper›PMID 34927448›Full record

Observational studyAmerican journal of physiology. Renal physiology2022

Proteinuria is accompanied by intratubular complement activation and apical membrane deposition of C3dg and C5b-9 in kidney transplant recipients.

Gustaf L Isaksson, Marie B Nielsen, Gitte R Hinrichs, Nicoline V Krogstrup, Rikke Zachar, Heidi Stubmark, Per Svenningsen, Kirsten Madsen, Claus Bistrup, Bente Jespersen and 4 more

Open access · hybridAbstract readObservational Study
In one paragraph

Observational study in American journal of physiology. Renal physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

14 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Role of local complement activation in kidney fibrosis and repair.The Journal of clinical investigation · 2025
    Review
  7. Crosstalk between glomeruli and tubules.Nature reviews. Nephrology · 2025
    Review
  8. Article
  9. Uromodulin and the study of urinary extracellular vesicles.Journal of extracellular biology · 2024
    Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
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

14 authors at 3 institutions in 1 country.

Gustaf L IsakssonDepartment of Molecular Medicine-Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.ORCID 0000-0003-0774-6772
Marie B NielsenDepartment of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
Gitte R HinrichsDepartment of Molecular Medicine-Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.ORCID 0000-0003-0526-7874
Nicoline V KrogstrupDepartment of Nephrology, Rigshospitalet, Copenhagen, Denmark.
Rikke ZacharDepartment of Molecular Medicine-Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.
Heidi StubmarkDepartment of Molecular Medicine-Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.
Per SvenningsenDepartment of Molecular Medicine-Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.ORCID 0000-0001-6590-7103
Kirsten MadsenDepartment of Molecular Medicine-Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.
Claus BistrupDepartment of Nephrology, Odense University Hospital, Odense, Denmark.ORCID 0000-0002-9280-916X
Bente JespersenDepartment of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
Henrik BirnDepartment of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
Yaseelan PalarasahDepartment of Molecular Medicine-Cancer and Inflammation Research, University of Southern Denmark, Odense, Denmark.
Boye L JensenDepartment of Molecular Medicine-Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.ORCID 0000-0001-7607-213X
CONTEXT Study Group
University of Southern Denmark · DKAarhus University · DKRigshospitalet · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proteinuria predicts accelerated decline in kidney function in kidney transplant recipients (KTRs). We hypothesized that aberrant filtration of complement factors causes intraluminal activation, apical membrane attack on tubular cells, and progressive injury. Biobanked samples from two previous studies in albuminuric KTRs were used. The complement-activation split products C3c, C3dg, and soluble C5b-9-associated C9 neoantigen were analyzed by ELISA in urine and plasma using neoepitope-specific antibodies. Urinary extracellular vesicles (uEVs) were enriched by lectin and immunoaffinity isolation and analyzed by immunoblot analysis. Urine complement excretion increased significantly in KTRs with an albumin-to-creatinine ratio of ≥300 mg/g compared with <30 mg/g. Urine C3dg and C9 neoantigen excretion correlated significantly to changes in albumin excretion from 3 to 12 mo after transplantation. Fractional excretion of C9 neoantigen was significantly higher than for albumin, indicating postfiltration generation. C9 neoantigen was detected in uEVs in six of the nine albuminuric KTRs but was absent in non-albuminuric controls (

Indexed as

Complement ActivationAdolescentAdultAgedAlbuminuriaCell MembraneComplement C3bComplement Membrane Attack ComplexCross-Sectional StudiesEpithelial CellsExtracellular VesiclesHumansKidney TransplantationKidney Tubules, ProximalMiddle AgedPeptide FragmentsComplement C3bcomplement C3d,gComplement Membrane Attack ComplexPeptide FragmentsSC5b-9 protein complexcomplement systemkidneykidney transplant recipientproteinuriaurine extracellular vesicle (exosome)

Identifiers

PMID34927448
PMCPMC8791842
OpenAlexW4200409823

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.