Background: Chronic Kidney Disease (CKD), is often detected late due to its asymptomatic nature in the early stage of the disease. Overproduction of reactive oxygen species contributes to various pathological processes through oxidative stress (OS), impacting on cellular structures and functions with previous studies suggesting a link between OS and CKD progression. This study investigated the association between serum peroxiredoxin-4 (Prx4), a biomarker of oxidative stress, and the development of CKD in the general population. Methods: This study featured data from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, involving 5341 participants without CKD at baseline who underwent extensive prospective health evaluations. Serum Prx4 levels were quantified using an immunoluminometric assay. The primary outcome was new-onset CKD as defined by the composite of urinary albumin excretion (UAE) > 30 mg/24-h, an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2), or both. Results: Baseline median Prx4 level was 0.65 [interquartile range (IQR): 0.42-1.04] U/L, median eGFR was 98 [IQR: 87-108] mL/min/1.73 m(2), and median UAE was 8.1 [IQR: 6.0-12.1] mg/L. During a median follow-up of 10.4 [IQR: 6.3-11.4] years, 867 (16.2 %) patients developed new-onset CKD. Higher Prx4 levels were significantly associated with an increased risk of CKD (hazard ratio (HR) per doubling: 1.29 [95 % confidence interval (CI): 1.21-1.37], p < 0.001), also after adjustment for risk factors including sex, smoking status, systolic blood pressure, high-sensitive C-reactive protein, chronic heart failure, diabetes mellitus and dyslipidemia (HR per doubling: 1.16 [1.06-1.24], p < 0.001). Sensitivity analyses confirmed the robustness of these findings. Conclusions: This study supports the hypothesis that systemic oxidative stress, reflected by higher serum Prx4 levels, is significantly associated with the risk of developing CKD in the general population. These findings suggest that Prx4 could be a valuable biomarker for early risk stratification and prevention strategies in CKD management.

Oxidative stress is a key pathophysiological process associated with the development and progression of inflammatory bowel disease (IBD). Biomarkers for oxidative stress, however, are scarce, as are diagnostic tools that can interrogate an individual’s gut redox status. This proof-of-concept study aimed to evaluate the potential utility of an oxidation-reduction potential (ORP) measurement probe, to quantify redox status in the feces of both patients with IBD and healthy controls. Previous studies using this ORP measurement probe demonstrated promising data when comparing ORP from severely malnourished individuals with that of healthy controls. To date, ORP analyses have not been performed in the context of IBD. We hypothesized that measuring the ORP of fecal water in patients with IBD might have diagnostic value. The current study, however, did not show significant differences in ORP measurement values between patients with IBD (median [IQR] 46.5 [33.0–61.2] mV) and healthy controls (25 [8.0–52.0] mV; p = 0.221). Additionally, ORP measurements were highly unstable and rapidly fluctuated throughout time, with ORP values varying from +24 to +303 mV. Due to potential biological processes and limitations of the measuring equipment, this study was unable to reliably measure ORP. As a result, our findings indicate that ORP quantification may not be a suitable method for assessing fecal redox status and, therefore, does not currently support further exploration as a diagnostic or monitoring tool.