Terje Apeland1, Mohammad A Mansoor2, Jessica Furriol3, Anastasia Ushakova4, Grete Jonsson5, Kari W Stangeland6, Hans-Peter Marti3. 1. Department of Medicine, Stavanger University Hospital, Stavanger, Norway. Electronic address: terje.apeland@lyse.net. 2. Department of Natural Sciences, University of Agder, Kristiansand, Norway. 3. Department of Medicine, Haukeland University Hospital, Bergen, Norway. 4. Department of Research, Stavanger University Hospital, Stavanger, Norway. 5. Department of Medical Biochemistry, Stavanger University Hospital, Stavanger, Norway. 6. Department of Medicine, Stavanger University Hospital, Stavanger, Norway.
Abstract
BACKGROUND: IgA nephropathy (IGAN) is characterized by oxidative stress and inflammation. In the present study, we explored the relationship of redox status vs. that of circulating inflammation-related factors with other biomarkers in patients with IGAN. METHODS: This is a case-control study comparing patients with IGAN (Stage 1-4) to healthy controls. Forty patients and 40 controls were matched for age and sex. Two circulating dynamic redox parameters were analysed: oxidized free cysteine (Cys) and nitrate. Thirty-seven inflammation-related factors were measured in serum. RESULTS: The patients had elevated levels of oxidized free Cys and nitrate, indicating the presence of oxidative stress. Nine circulating inflammation-related factors were higher in the serum of patients than in that of controls. The most important factors were APRIL, MMP-3, osteopontin, TNFR1 and TWEAK. Inflammation-related factors were positively correlated with oxidized free Cys, nitrate, creatinine and parathyroid hormone (PTH) in the patients. The correlation coefficients of Latent Inflammatory Factor vs. oxidized free Cys and nitrate were r = 0.43 (p = 0.007) and r = 0.51 (p = 0.001), respectively. This finding persisted after adjusting for the glomerular filtration rate. CONCLUSIONS: Patients with IGAN had disturbed redox status. Several circulating inflammation-related factors were elevated, suggesting activation of the non-canonical NF-kB pathway. There was a positive relationship between systemic redox status and the level of inflammation-related factors, partially independent of GFR. The present findings raise the question of whether circulating oxidized free Cys and/or nitrate may be employed as prognostic biomarkers for IGAN in the future.
BACKGROUND:IgAnephropathy (IGAN) is characterized by oxidative stress and inflammation. In the present study, we explored the relationship of redox status vs. that of circulating inflammation-related factors with other biomarkers in patients with IGAN. METHODS: This is a case-control study comparing patients with IGAN (Stage 1-4) to healthy controls. Forty patients and 40 controls were matched for age and sex. Two circulating dynamic redox parameters were analysed: oxidized free cysteine (Cys) and nitrate. Thirty-seven inflammation-related factors were measured in serum. RESULTS: The patients had elevated levels of oxidized free Cys and nitrate, indicating the presence of oxidative stress. Nine circulating inflammation-related factors were higher in the serum of patients than in that of controls. The most important factors were APRIL, MMP-3, osteopontin, TNFR1 and TWEAK. Inflammation-related factors were positively correlated with oxidized free Cys, nitrate, creatinine and parathyroid hormone (PTH) in the patients. The correlation coefficients of Latent Inflammatory Factor vs. oxidized free Cys and nitrate were r = 0.43 (p = 0.007) and r = 0.51 (p = 0.001), respectively. This finding persisted after adjusting for the glomerular filtration rate. CONCLUSIONS:Patients with IGAN had disturbed redox status. Several circulating inflammation-related factors were elevated, suggesting activation of the non-canonical NF-kB pathway. There was a positive relationship between systemic redox status and the level of inflammation-related factors, partially independent of GFR. The present findings raise the question of whether circulating oxidized free Cys and/or nitrate may be employed as prognostic biomarkers for IGAN in the future.