Journal article
Complement Activation in Patients with Focal Segmental Glomerulosclerosis
PloS one, Vol.10(9), pp.e0136558-e0136558
2015
DOI: 10.1371/journal.pone.0136558
PMCID: PMC4559462
PMID: 26335102
Abstract
Recent pre-clinical studies have shown that complement activation contributes to glomerular and tubular injury in experimental FSGS. Although complement proteins are detected in the glomeruli of some patients with FSGS, it is not known whether this is due to complement activation or whether the proteins are simply trapped in sclerotic glomeruli. We measured complement activation fragments in the plasma and urine of patients with primary FSGS to determine whether complement activation is part of the disease process.
Plasma and urine samples from patients with biopsy-proven FSGS who participated in the FSGS Clinical Trial were analyzed.
We identified 19 patients for whom samples were available from weeks 0, 26, 52 and 78. The results for these FSGS patients were compared to results in samples from 10 healthy controls, 10 patients with chronic kidney disease (CKD), 20 patients with vasculitis, and 23 patients with lupus nephritis.
Longitudinal control of proteinuria and estimated glomerular filtration rate (eGFR).
Levels of the complement fragments Ba, Bb, C4a, and sC5b-9 in plasma and urine.
Plasma and urine Ba, C4a, sC5b-9 were significantly higher in FSGS patients at the time of diagnosis than in the control groups. Plasma Ba levels inversely correlated with the eGFR at the time of diagnosis and at the end of the study. Plasma and urine Ba levels at the end of the study positively correlated with the level of proteinuria, the primary outcome of the study.
Limited number of patients with samples from all time-points.
The complement system is activated in patients with primary FSGS, and elevated levels of plasma Ba correlate with more severe disease. Measurement of complement fragments may identify a subset of patients in whom the complement system is activated. Further investigations are needed to confirm our findings and to determine the prognostic significance of complement activation in patients with FSGS.
Details
- Title: Subtitle
- Complement Activation in Patients with Focal Segmental Glomerulosclerosis
- Creators
- Joshua M Thurman - Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of AmericaMaria Wong - Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of AmericaBrandon Renner - Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of AmericaAshley Frazer-Abel - Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of AmericaPatricia C Giclas - Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of AmericaMelanie S Joy - Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of AmericaDiana Jalal - Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of AmericaMilena K Radeva - Cleveland Clinic Foundation, Cleveland, Ohio, United States of AmericaJennifer Gassman - Cleveland Clinic Foundation, Cleveland, Ohio, United States of AmericaDebbie S Gipson - Department of Pediatrics, CS Mott Children's Hospital, University of Michigan, Ann Arbor, Michigan, United States of AmericaFrederick Kaskel - Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, United States of AmericaAaron Friedman - Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, United States of AmericaHoward Trachtman - Department of Pediatrics, NYU Langone Medical Center, NYU School of Medicine, New York, New York, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.10(9), pp.e0136558-e0136558
- DOI
- 10.1371/journal.pone.0136558
- PMID
- 26335102
- PMCID
- PMC4559462
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science
- Grant note
- U01 DK063455 / NIDDK NIH HHS U01 DK063490 / NIDDK NIH HHS U01 DK063549 / NIDDK NIH HHS R01-DK076690 / NIDDK NIH HHS DK063490 / NIDDK NIH HHS U01-DK063385 / NIDDK NIH HHS DK063455 / NIDDK NIH HHS DK063549 / NIDDK NIH HHS R01 DK076690 / NIDDK NIH HHS U01 DK063385 / NIDDK NIH HHS
- Language
- English
- Date published
- 2015
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984094745002771
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