P0337PROTEOME CHANGES IN TUBULOINTERSTITIAL TISSUE OF PROGRESSIVE VS NON-PROGRESSIVE IGAN

Abstract

Abstract Background and Aims IgA nephropathy (IgAN), a common glomerulonephritis worldwide, is associated with a significant risk of progression to end-stage renal failure. In the Oxford classification, tubular atrophy is an established important risk factor for the risk of progression but few studies have investigated possible tubulointerstitial markers and the mechanisms of progression in IgAN. The present study investigated changes in the tubulointerstitial proteome from patients with IgAN. Method Based on data from the Norwegian Kidney Biopsy Registry and the Norwegian Renal Registry, two groups were included: IgAN patients with (n=9) or without (n=16) progression to ESRD during 10 years. Tubulointerstitial tissue without discernible interstitial expansion or pronounced tubular alterations were microdissected, proteome was analysed using mass spectrometry and protein abundances were compared between groups. Results: Proteomic analyses quantified 2562 proteins with 2 or more unique peptides . Of these, 201 proteins had significant different abundance between progressive and non-progressive IgAN patients, 96 were more abundant and 105 less abundant. Periostin was the protein with the highest fold change between progressive and non progressive IgAN (fc 9.59, p<0.05). Proteins related to inflammation were more abundant and proteins involved in the aerobic energy metabolism and energy demanding ion channels were significantly less abundant in progressive vs non-progressive patients. Conclusion Our study describes extensive proteome changes of tubulo-interstitial tissue in patients with progressive IgAN and indicates several proteins and pathways that are important in the progression of the disease.