Association of advanced vasculopathy and transforming growth factor-beta1 gene expression with immunoglobulin A nephropathy progression

Abstract

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.