Association of advanced vasculopathy and transforming growth factor-beta1 gene expression with immunoglobulin A nephropathy progression.
BACKGROUND
The mechanism of IgA nephropathy (IgAN) progression remains ill-defined. In this prospective study, the prognostic role of clinical, histological and molecular markers over a 2-year follow-up was evaluated.


METHODS
Fifty-one patients with biopsy-proven IgAN were followed for 24 months. Besides routine histology, the intrarenal gene expressions of cytokines and chemokines were quantified by reverse transcription quantitative real-time polymerase chain reaction, and the presence of lymphocytes and macrophages were immunohistochemically examined.


RESULTS
Higher transforming growth factor-β1 and severe chronic vasculopathy (but not glomerulosclerosis, interstitial fibrosis or lymphocyte infiltrate) were associated with the IgAN progression 24 months after biopsy. The gene expression of chemokine (C-C motif) ligands 2 and 5, hepatocyte growth factor, bone morphogenic protein-7 and transforming growth factor-β1 and the interstitial infiltrate of T and B lymphocytes and macrophages were significantly associated with serum creatinine and glomerular filtration rate at the time of biopsy. The intrarenal chemokine (C-C motif) ligand 2 and hepatocyte growth factor gene expression were associated with the proteinuria.


CONCLUSIONS
Besides the known risk factors for chronic kidney disease, advanced vasculopathy and molecular signatures of fibrogenesis were associated with the IgAN progression.
Brabcova
Irena
I
Transplant Laboratory, Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Tesar
Vladimir
V
Honsova
Eva
E
Lodererova
Alena
A
Novotna
Eva
E
Maixnerova
Dita
D
Merta
Miroslav
M
Bürgelova
Marcela
M
Hribova
Petra
P
Skibova
Jelena
J
Zadrazil
Josef
J
Maly
Jan
J
Viklicky
Ondrej
O
D000328:Adult; D001706:Biopsy; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014652:Vascular Diseases / Q000235:genetics / Q000473:pathology*
D053773:Transforming Growth Factor beta1