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2015 ; 10
(9
): e0136558
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Complement Activation in Patients with Focal Segmental Glomerulosclerosis
#MMPMID26335102
Thurman JM
; Wong M
; Renner B
; Frazer-Abel A
; Giclas PC
; Joy MS
; Jalal D
; Radeva MK
; Gassman J
; Gipson DS
; Kaskel F
; Friedman A
; Trachtman H
PLoS One
2015[]; 10
(9
): e0136558
PMID26335102
show ga
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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