Connective tissue growth factor and the cicatrization of cellular crescents in ANCA-associated glomerulonephritis.
BACKGROUND
Outcome in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AGN) is difficult to predict. Scoring of renal biopsies has significant but limited predictive value. We investigated whether analysis of plasma and urine levels, and immunostaining of biopsies for the pro-fibrotic peptide connective tissue growth factor (CTGF), might improve prediction of renal outcome.


METHODS
ANCA-positive patients were included. Renal biopsies were classified according to the AGN classification. Biopsies were stained for CTGF protein. CTGF was measured by ELISA at the time of renal biopsy in plasma and urine, and during follow-up in plasma.


RESULTS
Eighty-two patients were included. CTGF staining was positive in crescentic lesions. Plasma CTGF at the time of renal biopsy was 2.4 ± 1.7 pmol/mL when compared with 0.5 ± 0.0 pmol/mL in healthy controls (P < 0.01). Plasma CTGF was associated with cellular crescents, but not when corrected for renal function. Plasma CTGF at baseline was associated with fibrous crescents in the follow-up biopsy, also after correction for renal function. Plasma CTGF at baseline predicted renal survival more accurately than the AGN classification.


CONCLUSIONS
In AGN patients, CTGF was overexpressed in crescentic glomeruli. Baseline plasma CTGF predicted the percentage of fibrous crescents in later biopsies, and renal survival, suggesting that CTGF is involved in the cicatrization, as opposed to resolution of cellular crescents in AGN.
Clinical and Experimental Immunology, Maastricht University, Maastricht, The Netherlands.
Marc
M
Hilhorst
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Helena M
HM
Kok
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Roel
R
Broekhuizen
Clinical and Experimental Immunology, Maastricht University, Maastricht, The Netherlands.
Pieter
P
van Paassen
Clinical and Experimental Immunology, Maastricht University, Maastricht, The Netherlands.
Peter
P
van Breda Vriesman
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Roel
R
Goldschmeding
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
Tri Q
TQ
Nguyen
Clinical and Experimental Immunology, Maastricht University, Maastricht, The Netherlands.
Jan Willem
JW
Cohen Tervaert
D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001706:Biopsy; D016022:Case-Control Studies; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology*; D055513:Connective Tissue Growth Factor / Q000097:blood* / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D005921:Glomerulonephritis / Q000097:blood / Q000175:diagnosis* / Q000401:mortality / Q000652:urine; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; C526317:CCN2 protein, human; D055513:Connective Tissue Growth Factor
ANCA; CTGF; glomerulonephritis; renal biopsy; vasculitis