Complement Activation in Patients with Focal Segmental Glomerulosclerosis.
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.


METHODS
Plasma and urine samples from patients with biopsy-proven FSGS who participated in the FSGS Clinical Trial were analyzed.


METHODS
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.


RESULTS
Longitudinal control of proteinuria and estimated glomerular filtration rate (eGFR).


METHODS
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.


CONCLUSIONS
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.
Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Joshua M
JM
Thurman
Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Maria
M
Wong
Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Brandon
B
Renner
Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of America.
Ashley
A
Frazer-Abel
Department of Pediatrics, National Jewish Health, Denver, Colorado, United States of America.
Patricia C
PC
Giclas
Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Melanie S
MS
Joy
Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Diana
D
Jalal
Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.
Milena K
MK
Radeva
Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.
Jennifer
J
Gassman
Department of Pediatrics, CS Mott Children's Hospital, University of Michigan, Ann Arbor, Michigan, United States of America.
Debbie S
DS
Gipson
Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Frederick
F
Kaskel
Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
Aaron
A
Friedman
Department of Pediatrics, NYU Langone Medical Center, NYU School of Medicine, New York, New York, United States of America.
Howard
H
Trachtman
D000293:Adolescent; D000328:Adult; D002648:Child; D003167:Complement Activation; D050776:Complement C5b / Q000378:metabolism / Q000652:urine; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood* / Q000652:urine*; D006801:Humans; D008297:Male
D050776:Complement C5b