Oxidative stress and macrophage infiltration in IgA nephropathy
Yaşar Çalışkan, Erol Demir, Ecem Karatay, Yasemin Özlük, Şafak Mirioğlu, Ahmet Burak Dirim, Ayşe Serra Artan, Sebahat Usta Akgül, Özgür Akın Oto, Fatma Savran Oğuz, Aydın Türkmen, Krista L. Lentine, Halil Yazıcı
Abstract
BACKGROUND: The aim of this study was to evaluate the interactions among serum levels of galactose-deficient IgA1 (Gd-IgA1), oxidative stress and macrophage infiltration and their clinical correlates in patients with IgA Nephropathy (IgAN). METHODS: A total of 47 patients with biopsy-proven primary IgAN, aged between 16 and 79 years, with a follow-up period ≥ 1 year or who showed progression to end stage kidney disease (ESKD) regardless the duration of follow-up were included. Study endpoint was the progression to ESKD. Serum Gd-IgA1 and advanced oxidation protein product (AOPP) levels were measured using ELISA assays. Kidney biopsies were evaluated according to the Oxford MEST-C scoring, with C4d and CD68 staining. RESULTS: Seventeen patients (36%) experienced ESKD during a median follow-up time of 6 years (IQR 3.7-7.5). Serum AOPP levels were correlated with the intensity of glomerular C3 deposition (r = 0.325, p = 0.026), glomerular (r = 0.423, p = 0.003) and interstitial CD68 + cell count (r = 0.298, p = 0.042) and Gd-IgA1 levels (r = 0.289, p = 0.049). Serum Gd-IgA1 levels were correlated with the intensity of C3 deposition (r = 0.447, p = 0.002). eGFR at biopsy (adjusted HR (aHR) 0.979 p = 0.011), and E score (aHR, 8.305, p = 0.001) were associated with progression to ESKD in multivariate analysis. 5-year ESKD-free survival rate was significantly lower in patients with higher E score compared to patients with E score 0 [p = 0.021]. CONCLUSIONS: An increased number of macrophages in the glomerular and tubulointerstitial area may play a role in oxidative stress and complement system activation. Endocapillary hypercellularity is a predictive factor for poor prognosis in IgAN.