Evidence map›Paper›PMID 26940098›Full record

ArticleJournal of the American Society of Nephrology : JASN2016

Proteomics of Urinary Vesicles Links Plakins and Complement to Polycystic Kidney Disease.

Mahdi Salih, Jeroen A Demmers, Karel Bezstarosti, Wouter N Leonhard, Monique Losekoot, Cees van Kooten, Ron T Gansevoort, Dorien J M Peters, Robert Zietse, Ewout J Hoorn and 1 more

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In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.

  1. Guideline
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Urinary exosomes as promising biomarkers for early kidney disease detection.American journal of clinical and experimental urology · 2025
    Review
  9. Urinary extracellular vesicles in childhood kidney diseases.Pediatric nephrology (Berlin, Germany) · 2024
    Review
  10. Article
  11. Article
  12. Review
  13. Extracellular Vesicles as Source of Biomarkers in Glomerulonephritis.International journal of molecular sciences · 2023
    Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Review
  20. Extracellular Vesicles and Hypertension.Advances in experimental medicine and biology · 2023
    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

11 authors at 4 institutions in 2 countries.

Mahdi SalihDepartment of Internal Medicine, Division of Nephrology & Transplantation, and.
Jeroen A DemmersProteomics Center, Erasmus Medical Center, Rotterdam, The Netherlands.
Karel BezstarostiProteomics Center, Erasmus Medical Center, Rotterdam, The Netherlands.
Wouter N LeonhardDepartments of Human Genetics.
Monique LosekootClinical Genetics, and.
Cees van KootenNephrology, Leiden University Medical Center, Leiden, The Netherlands; and.
Ron T GansevoortDepartment of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
Dorien J M PetersDepartments of Human Genetics.
Robert ZietseDepartment of Internal Medicine, Division of Nephrology & Transplantation, and.
Ewout J HoornDepartment of Internal Medicine, Division of Nephrology & Transplantation, and e.j.hoorn@erasmusmc.nl.
DIPAK Consortium
Erasmus MC · NLLeiden University Medical Center · NLPediatrics and Genetics · USUniversity Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Novel therapies in autosomal dominant polycystic kidney disease (ADPKD) signal the need for markers of disease progression or response to therapy. This study aimed to identify disease-associated proteins in urinary extracellular vesicles (uEVs), which include exosomes, in patients with ADPKD. We performed quantitative proteomics on uEVs from healthy controls and patients with ADPKD using a labeled approach and then used a label-free approach with uEVs of different subjects (healthy controls versus patients with ADPKD versus patients with non-ADPKD CKD). In both experiments, 30 proteins were consistently more abundant (by two-fold or greater) in ADPKD-uEVs than in healthy- and CKD-uEVs. Of these proteins, we selected periplakin, envoplakin, villin-1, and complement C3 and C9 for confirmation because they were also significantly overrepresented in pathway analysis and were previously implicated in ADPKD pathogenesis. Immunoblotting confirmed higher abundances of the selected proteins in uEVs from three independent groups of patients with ADPKD. Whereas uEVs of young patients with ADPKD and preserved kidney function already had higher levels of complement, only uEVs of patients with advanced stages of ADPKD had increased levels of villin-1, periplakin, and envoplakin. Furthermore, all five proteins correlated positively with total kidney volume. Analysis in kidney tissue from mice with kidney-specific, tamoxifen-inducible Pkd1 deletion demonstrated higher expression in more severe stages of the disease and correlation with kidney weight for each protein of interest. In summary, proteomic analysis of uEVs identified plakins and complement as disease-associated proteins in ADPKD. These proteins are new candidates for evaluation as biomarkers or targets for therapy in ADPKD.

Indexed as

Extracellular VesiclesProteomicsAnimalsComplement C3Complement C9HumansMicePlakinsPolycystic Kidney, Autosomal DominantUrineComplement C3Complement C9PlakinsADPKDcomplementcytoskeletongenetic renal disease

Identifiers

PMID26940098
PMCPMC5042669
OpenAlexW2292155255

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.