support@icr-heart.com
|
FAQs
Oxidative stress is increasingly recognised as an important contributor to the progression and systemic complications of chronic kidney disease (CKD). Increased generation of reactive oxygen species combined with inadequate antioxidant defence may result in lipid peroxidation, oxidative DNA damage, inflammation and cardiovascular complications. Objective: To compare oxidative stress and antioxidant defence markers between patients with CKD and healthy controls and to evaluate their relationship with the severity of renal dysfunction. Materials and Methods: This hospital-based analytical case–control study included 120 participants, comprising 60 patients with CKD and 60 age- and sex-matched apparently healthy controls. Serum malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were evaluated as markers of lipid peroxidation and oxidative DNA damage. Superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and total antioxidant capacity were assessed as indices of antioxidant defence. Renal function was evaluated using serum creatinine, blood urea and estimated glomerular filtration rate (eGFR). CKD patients were further analysed according to disease stage and dialysis status. Results: MDA levels were significantly higher in CKD patients than controls (6.90 ± 1.84 vs 3.20 ± 0.91 nmol/mL; p<0.001). Similarly, 8-OHdG was significantly elevated (12.80 ± 4.16 vs 5.60 ± 1.87 ng/mL; p<0.001). Antioxidant defence was markedly impaired: SOD was 4.90 ± 1.31 versus 7.80 ± 1.52 U/mL, catalase 34.1 ± 9.7 versus 51.6 ± 11.2 U/mL, GPx 425 ± 118 versus 612 ± 134 U/L and total antioxidant capacity 0.89 ± 0.24 versus 1.42 ± 0.31 mmol/L in CKD patients and controls, respectively (all p<0.001). MDA and 8-OHdG progressively increased with advancing CKD stage, whereas SOD declined. eGFR correlated negatively with MDA (r=−0.68, p<0.001) and 8-OHdG (r=−0.62, p<0.001). Conclusion: CKD is associated with substantial oxidative stress and impairment of endogenous antioxidant defence. The progressive increase in oxidative injury with declining renal function suggests that MDA and 8-OHdG may serve as supplementary biomarkers of oxidative burden and disease severity in CKD.
Chronic kidney disease is a progressive disorder characterised by persistent structural or functional abnormalities of the kidneys and is associated with substantial morbidity and mortality worldwide. Diabetes mellitus and hypertension remain major contributors to CKD, while cardiovascular disease constitutes one of its most important complications.¹˒²
Oxidative stress represents an important biological mechanism contributing to progressive renal dysfunction. It develops when the production of reactive oxygen species exceeds the capacity of endogenous antioxidant systems to neutralise them. CKD provides a favourable environment for oxidative stress because of uraemic toxin accumulation, mitochondrial dysfunction, activation of NADPH oxidases, inflammation, disturbances of iron metabolism and loss of antioxidant substances.³
Malondialdehyde is generated during lipid peroxidation and is widely used as an indicator of oxidative injury. Oxidative damage also affects nucleic acids, resulting in the production of 8-hydroxy-2′-deoxyguanosine, an established marker of oxidative DNA injury. Previous studies have demonstrated increased oxidative damage in patients with CKD and chronic renal failure.⁴˒⁵
In parallel, antioxidant defence systems such as superoxide dismutase, catalase and glutathione peroxidase may become impaired. Reduced antioxidant activity may further increase cellular susceptibility to oxidative damage, creating a self-perpetuating cycle of oxidative stress, inflammation and progressive tissue injury.³˒⁶
The present study therefore evaluated oxidative stress and antioxidant defence among patients with different stages of CKD and compared these parameters with apparently healthy controls.
A hospital-based analytical observational study with a case–control design was conducted. A total of 120 participants were included, comprising 60 patients with established CKD and 60 age- and sex-matched apparently healthy controls.
Adults with established CKD were included according to accepted criteria based on persistent reduction in renal function and/or markers of kidney damage. Patients with acute kidney injury, active malignancy, acute infection or inflammatory illness, major chronic diseases independently influencing oxidative stress, current smoking, chronic alcohol use and recent use of high-dose antioxidant supplementation were excluded.
Following overnight fasting, venous blood samples were collected under aseptic conditions. In maintenance haemodialysis patients, samples were obtained before a mid-week dialysis session.
Routine biochemical assessment included serum creatinine, blood urea, haemoglobin, electrolytes, fasting lipid profile and high-sensitivity C-reactive protein. eGFR was calculated using the CKD-EPI equation.
MDA was assessed as a marker of lipid peroxidation using the thiobarbituric acid reactive substances method. Serum 8-OHdG was measured by validated enzyme-linked immunosorbent assay. SOD, catalase, GPx and total antioxidant capacity were measured using standard spectrophotometric or kit-based methods.
Continuous variables were expressed as mean ± standard deviation. Appropriate parametric or non-parametric tests were used for comparisons. Pearson or Spearman correlation was used according to data distribution. A two-sided p-value <0.05 was considered statistically significant.
The mean age, sex distribution and body mass index were comparable between cases and controls. Patients with CKD demonstrated markedly impaired renal function, with mean serum creatinine of 5.80 ± 3.21 mg/dL compared with 0.86 ± 0.16 mg/dL among controls. Mean eGFR was 18.7 ± 12.9 compared with 103.8 ± 11.7 mL/min/1.73 m².
Table 1. Oxidative stress markers in CKD patients and controls
|
Marker |
CKD patients (n=60) |
Controls (n=60) |
p-value |
|
MDA (nmol/mL) |
6.90 ± 1.84 |
3.20 ± 0.91 |
<0.001 |
|
8-OHdG (ng/mL) |
12.80 ± 4.16 |
5.60 ± 1.87 |
<0.001 |
Both markers of oxidative injury were significantly increased in patients with CKD, indicating enhanced lipid peroxidation and oxidative DNA damage.
Table 2. Antioxidant defence markers
|
Marker |
CKD patients |
Controls |
p-value |
|
SOD (U/mL) |
4.90 ± 1.31 |
7.80 ± 1.52 |
<0.001 |
|
Catalase (U/mL) |
34.1 ± 9.7 |
51.6 ± 11.2 |
<0.001 |
|
GPx (U/L) |
425 ± 118 |
612 ± 134 |
<0.001 |
|
Total antioxidant capacity (mmol/L) |
0.89 ± 0.24 |
1.42 ± 0.31 |
<0.001 |
All measured antioxidant parameters were significantly lower among CKD patients.
Table 3. Oxidative stress according to CKD stage
|
CKD stage |
MDA (nmol/mL) |
8-OHdG (ng/mL) |
SOD (U/mL) |
|
Stage 3a |
4.70 ± 0.82 |
8.2 ± 2.1 |
6.20 ± 1.10 |
|
Stage 3b |
5.30 ± 1.01 |
9.5 ± 2.5 |
5.70 ± 1.08 |
|
Stage 4 |
6.20 ± 1.24 |
11.4 ± 3.0 |
5.10 ± 1.12 |
|
Stage 5, non-dialysis |
7.40 ± 1.38 |
13.7 ± 3.4 |
4.50 ± 1.01 |
|
Stage 5D haemodialysis |
8.10 ± 1.56 |
15.2 ± 3.8 |
4.10 ± 0.92 |
|
p for trend |
<0.001 |
<0.001 |
<0.001 |
A graded increase in oxidative injury and decline in antioxidant defence occurred with advancing CKD stage.
The present study demonstrated a pronounced imbalance between oxidative stress and antioxidant defence in CKD. Both MDA and 8-OHdG were substantially elevated, whereas SOD, catalase, GPx and total antioxidant capacity were reduced.
The elevated MDA concentrations indicate increased lipid peroxidation. Chugh et al. similarly documented increased oxidative stress among Indian patients with chronic renal failure and reported further alteration following haemodialysis.⁴ Mimić-Oka et al. demonstrated altered antioxidant capacity across varying degrees of chronic renal failure, supporting the concept that redox imbalance becomes progressively more prominent as kidney function deteriorates.⁵
The elevation of 8-OHdG provides evidence that oxidative injury in CKD extends beyond lipid membranes to DNA. Akagi et al. demonstrated that 8-OHdG levels correlated with biochemical indices of uraemia and renal dysfunction in chronic renal failure.⁷
The present study also demonstrated substantially reduced antioxidant enzyme activities. This suggests that oxidative stress in CKD is attributable not only to increased oxidant generation but also to inadequate endogenous antioxidant defence. Previous research has similarly demonstrated abnormalities of SOD, GPx and antioxidant capacity in renal failure.³˒⁵
A particularly important observation was the graded increase in MDA and 8-OHdG from Stage 3a to Stage 5D, together with progressive reduction in SOD. The inverse correlation between eGFR and MDA further indicates that the oxidative burden becomes increasingly severe as filtration capacity declines.
Patients undergoing maintenance haemodialysis showed the greatest oxidative abnormalities. This may reflect advanced renal failure, uraemic toxin accumulation and inflammation as well as repeated exposure to extracorporeal circulation and loss of water-soluble antioxidants.
The study is limited by its observational case–control design, which does not establish causality. Measurement at a single time point also prevents assessment of the prognostic significance of the biomarkers.
Patients with CKD demonstrate significantly increased lipid peroxidation and oxidative DNA damage together with impaired endogenous antioxidant defence. Oxidative abnormalities become progressively greater as kidney function declines and are particularly pronounced in advanced CKD and haemodialysis patients. MDA, 8-OHdG and antioxidant enzyme activity may therefore provide useful supplementary information regarding the oxidative burden associated with CKD.
Download PDF
Download PDF
Download PDF
Download PDF
Download XML
