Abstract
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 5,341 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 m2, 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/1.73m2, 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.
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 5,341 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 m2, 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/1.73m2, 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.
| Original language | English |
|---|---|
| Article number | 103408 |
| Number of pages | 10 |
| Journal | Redox Biology |
| Volume | 77 |
| Early online date | 22-Oct-2024 |
| DOIs | |
| Publication status | Published - Nov-2024 |
Keywords
- Humans
- Biomarkers/blood
- Renal Insufficiency, Chronic/blood
- Oxidative Stress
- Male
- Female
- Peroxiredoxins/blood
- Middle Aged
- Glomerular Filtration Rate
- Aged
- Prospective Studies
- Cohort Studies
- Adult
- Risk Factors