Complement activation in patients with focal segmental glomerulosclerosis

Joshua M. Thurman, Maria Wong, Brandon Renner, Ashley Frazer-Abel, Patricia C. Giclas, Melanie S. Joy, Diana Jalal, Milena K. Radeva, Jennifer Gassman, Debbie S. Gipson, Frederick J. Kaskel, Aaron Friedman, Howard Trachtman

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background. 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. Study Design. Plasma and urine samples from patients with biopsy-proven FSGS who participated in the FSGS Clinical Trial were analyzed. Setting and Participants. 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. Outcomes. Longitudinal control of proteinuria and estimated glomerular filtration rate (eGFR). Measurements. Levels of the complement fragments Ba, Bb, C4a, and sC5b-9 in plasma and urine. Results. 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. Limitations. Limited number of patients with samples from all time-points. Conclusions. 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.

Original languageEnglish (US)
Article numbere0136558
JournalPLoS One
Volume10
Issue number9
DOIs
StatePublished - Sep 3 2015

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Focal Segmental Glomerulosclerosis
Complement Activation
complement
Chemical activation
Plasmas
urine
Urine
Longitudinal control
glomerular filtration rate
Biopsy
Glomerular Filtration Rate
Proteinuria
clinical trials
Complement System Proteins
sampling
vasculitis
nephritis
Lupus Nephritis
Vasculitis
kidney diseases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Thurman, J. M., Wong, M., Renner, B., Frazer-Abel, A., Giclas, P. C., Joy, M. S., ... Trachtman, H. (2015). Complement activation in patients with focal segmental glomerulosclerosis. PLoS One, 10(9), [e0136558]. https://doi.org/10.1371/journal.pone.0136558

Complement activation in patients with focal segmental glomerulosclerosis. / Thurman, Joshua M.; Wong, Maria; Renner, Brandon; Frazer-Abel, Ashley; Giclas, Patricia C.; Joy, Melanie S.; Jalal, Diana; Radeva, Milena K.; Gassman, Jennifer; Gipson, Debbie S.; Kaskel, Frederick J.; Friedman, Aaron; Trachtman, Howard.

In: PLoS One, Vol. 10, No. 9, e0136558, 03.09.2015.

Research output: Contribution to journalArticle

Thurman, JM, Wong, M, Renner, B, Frazer-Abel, A, Giclas, PC, Joy, MS, Jalal, D, Radeva, MK, Gassman, J, Gipson, DS, Kaskel, FJ, Friedman, A & Trachtman, H 2015, 'Complement activation in patients with focal segmental glomerulosclerosis', PLoS One, vol. 10, no. 9, e0136558. https://doi.org/10.1371/journal.pone.0136558
Thurman JM, Wong M, Renner B, Frazer-Abel A, Giclas PC, Joy MS et al. Complement activation in patients with focal segmental glomerulosclerosis. PLoS One. 2015 Sep 3;10(9). e0136558. https://doi.org/10.1371/journal.pone.0136558
Thurman, Joshua M. ; Wong, Maria ; Renner, Brandon ; Frazer-Abel, Ashley ; Giclas, Patricia C. ; Joy, Melanie S. ; Jalal, Diana ; Radeva, Milena K. ; Gassman, Jennifer ; Gipson, Debbie S. ; Kaskel, Frederick J. ; Friedman, Aaron ; Trachtman, Howard. / Complement activation in patients with focal segmental glomerulosclerosis. In: PLoS One. 2015 ; Vol. 10, No. 9.
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AU - Wong, Maria

AU - Renner, Brandon

AU - Frazer-Abel, Ashley

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AU - Joy, Melanie S.

AU - Jalal, Diana

AU - Radeva, Milena K.

AU - Gassman, Jennifer

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AU - Kaskel, Frederick J.

AU - Friedman, Aaron

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N2 - Background. 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. Study Design. Plasma and urine samples from patients with biopsy-proven FSGS who participated in the FSGS Clinical Trial were analyzed. Setting and Participants. 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. Outcomes. Longitudinal control of proteinuria and estimated glomerular filtration rate (eGFR). Measurements. Levels of the complement fragments Ba, Bb, C4a, and sC5b-9 in plasma and urine. Results. 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. Limitations. Limited number of patients with samples from all time-points. Conclusions. 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.

AB - Background. 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. Study Design. Plasma and urine samples from patients with biopsy-proven FSGS who participated in the FSGS Clinical Trial were analyzed. Setting and Participants. 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. Outcomes. Longitudinal control of proteinuria and estimated glomerular filtration rate (eGFR). Measurements. Levels of the complement fragments Ba, Bb, C4a, and sC5b-9 in plasma and urine. Results. 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. Limitations. Limited number of patients with samples from all time-points. Conclusions. 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.

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