Chronic kidney disease (CKD) is a major global public health problem associated with increasing morbidity, mortality, and healthcare burden. In addition to progressive loss of renal function, CKD is accompanied by systemic metabolic and cardiovascular complications that significantly affect patient outcomes. Traditional risk factors alone fail to fully explain the accelerated progression and high cardiovascular mortality observed in CKD, highlighting the role of non-traditional mechanisms such as oxidative stress.

Oxidative stress refers to an imbalance between the generation of reactive oxygen species (ROS) and the body’s antioxidant defense mechanisms. In CKD, excessive ROS production arises from mitochondrial dysfunction, chronic inflammation, uremic toxin accumulation, activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and impaired nitric oxide signaling. Concurrently, antioxidant defenses are compromised due to reduced activity of enzymatic antioxidants and depletion of non-enzymatic antioxidants.

The kidney is particularly vulnerable to oxidative injury because of its high metabolic activity and abundant mitochondrial content. Persistent oxidative stress promotes lipid peroxidation, protein oxidation, DNA damage, endothelial dysfunction, and activation of pro-fibrotic pathways, ultimately leading to glomerulosclerosis and tubulointerstitial fibrosis.

Malondialdehyde (MDA), a byproduct of lipid peroxidation, and advanced oxidation protein products (AOPPs), which reflect oxidative protein damage, are commonly used markers of oxidative stress. Antioxidant enzymes such as superoxide dismutase (SOD) and catalase play key roles in neutralizing ROS and maintaining redox homeostasis. Several studies have reported elevated oxidative stress markers and reduced antioxidant enzyme activity in CKD patients, particularly in advanced stages.

However, data evaluating oxidative stress and antioxidant imbalance across different CKD stages in Indian populations remain limited. Understanding these alterations may provide insights into disease progression and identify potential therapeutic targets. The present study aimed to assess oxidative stress markers and antioxidant enzyme levels across CKD stages and examine their relationship with renal function.

Study Design and Setting

This was a hospital-based cross-sectional observational study conducted in the outpatient and inpatient departments of a tertiary care teaching hospital.

Study Population

A total of 150 adult patients (≥18 years) diagnosed with CKD stages 1–5 were enrolled after obtaining informed written consent.

Inclusion Criteria

• Adults aged 18 years or older
• Diagnosed cases of CKD (Stages 1–5)
• Willingness to participate in the study

Exclusion Criteria

• Acute kidney injury
• Active infections or inflammatory conditions
• Malignancy
• Chronic liver disease
• Autoimmune disorders

Clinical and Laboratory Assessment

All participants underwent detailed clinical evaluation. Blood samples were collected for estimation of:

• Serum creatinine
• Estimated glomerular filtration rate (eGFR)
• Malondialdehyde (MDA)
• Advanced oxidation protein products (AOPPs)
• Superoxide dismutase (SOD)
• Catalase

CKD staging was performed according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines based on eGFR.

Statistical Analysis

Data were expressed as mean ± standard deviation. Comparison across CKD stages was performed using one-way analysis of variance (ANOVA). Pearson correlation coefficient was used to assess associations between oxidative stress markers, antioxidant enzymes, and eGFR. A p-value <0.05 was considered statistically significant.

The study population had a mean age of 52.8 ± 13.6 years, with a male predominance. Diabetes mellitus and hypertension were common comorbidities.

Renal function declined progressively with advancing CKD stage, as reflected by increasing serum creatinine and decreasing eGFR values (p < 0.001).

Oxidative stress markers showed a significant and progressive rise across CKD stages. Mean MDA levels increased from 2.1 ± 0.6 nmol/mL in Stage 1 to 10.3 ± 2.1 nmol/mL in Stage 5. Similarly, AOPPs increased from 45.3 ± 9.8 µmol/L in Stage 1 to 168.9 ± 22.7 µmol/L in Stage 5 (p < 0.001).

In contrast, antioxidant enzyme levels declined significantly with disease progression. Mean SOD levels decreased from 8.6 ± 1.9 U/mL in Stage 1 to 2.9 ± 0.9 U/mL in Stage 5, while catalase levels decreased from 56.4 ± 9.2 kU/L to 22.8 ± 5.3 kU/L (p < 0.001).

Correlation analysis revealed strong inverse relationships between eGFR and oxidative stress markers (MDA: r = −0.81; AOPPs: r = −0.77; p < 0.001). Antioxidant enzymes showed positive correlations with eGFR, indicating better antioxidant status with preserved renal function.

Table 1. Sociodemographic and Clinical Characteristics of the Study Population (n = 150)

Table 2. Distribution of Patients According to Chronic Kidney Disease Stages

Table 3. Renal Function Parameters Across CKD Stages

Table 4. Oxidative Stress Markers Across CKD Stages

Table 5. Antioxidant Enzyme Levels Across CKD Stages

Table 6. Correlation Between Oxidative Stress Markers and Renal Function

Table 7. Comparison of Oxidative Stress and Antioxidant Parameters in Early and Advanced CKD

This study demonstrates a clear association between oxidative stress, antioxidant depletion, and CKD severity. Oxidative stress markers increased significantly with advancing CKD stage, while antioxidant enzyme activity declined, reflecting progressive redox imbalance.

Elevated MDA levels indicate enhanced lipid peroxidation, which disrupts cellular membranes and promotes renal tissue injury. Increased AOPPs reflect oxidative modification of proteins, contributing to endothelial dysfunction and inflammation. The strong inverse correlation between oxidative stress markers and eGFR underscores their role in renal functional decline.

The observed reduction in SOD and catalase activity suggests impaired antioxidant defense mechanisms in CKD. Reduced antioxidant capacity may result from increased consumption of antioxidants, decreased synthesis, and uremia-related inhibition of enzyme activity.

These findings are consistent with previous studies reporting heightened oxidative stress in advanced CKD. The high prevalence of diabetes and hypertension in the study population may have further contributed to oxidative injury, as both conditions are known to enhance ROS production.

Targeting oxidative stress through lifestyle modification, optimization of metabolic control, and potential antioxidant therapies may help slow CKD progression. However, further longitudinal studies are needed to establish causality and therapeutic efficacy.

Oxidative stress increases and antioxidant defenses decline progressively with worsening chronic kidney disease. Elevated oxidative stress markers and reduced antioxidant enzyme levels are strongly associated with declining renal function. Assessment of oxidative stress parameters may aid in identifying patients at higher risk for disease progression and related complications.

1. Webster AC, Nagler EV, Morton RL, Masson P. Chronic kidney disease. Lancet. 2017;389(10075):1238–1252. doi:10.1016/S0140-6736(16)32064-5.
2. Daenen K, Andries A, Mekahli D, Van Schepdael A, Jouret F, Bammens B. Oxidative stress in chronic kidney disease. Pediatr Nephrol. 2019;34(6):975–991. doi:10.1007/s00467-018-4005-4.
3. Podkowińska A, Formanowicz D. Chronic kidney disease as oxidative stress. Antioxidants (Basel). 2020;9(8):752. doi:10.3390/antiox9080752.
4. Ratliff BB, Abdulmahdi W, Pawar R, Wolin MS. Oxidant mechanisms in renal injury and disease. Antioxid Redox Signal. 2016;25(3):119–146. doi:10.1089/ars.2015.6445.
5. Bhargava P, Schnellmann RG. Mitochondrial energetics in the kidney. Nat Rev Nephrol. 2017;13(10):629–646. doi:10.1038/nrneph.2017.107.
6. Ebert T, Pawelzik SC, Witasp A, et al. Inflammation and oxidative stress in chronic kidney disease. Antioxid Redox Signal. 2021;35(17):1426–1448. doi:10.1089/ars.2020.8184.
7. Krata N, Zagożdżon R, Foroncewicz B, Mucha K. Oxidative stress in kidney diseases: The cause or the consequence? Arch Immunol Ther Exp (Warsz). 2018;66(3):211–220. doi:10.1007/s00005-017-0450-1.
8. Stenvinkel P, Chertow GM, Devarajan P, et al. Chronic inflammation in chronic kidney disease progression. Kidney Int Rep. 2021;6(7):1775–1787. doi:10.1016/j.ekir.2021.04.023.
9. Verma S, Singh P, Khurana S, et al. Implications of oxidative stress in chronic kidney disease. Kidney Res Clin Pract. 2021;40(2):183–193. doi:10.23876/j.krcp.20.163.
10. Cobo G, Lindholm B, Stenvinkel P. Chronic inflammation in end-stage renal disease and dialysis. Nephrol Dial Transplant. 2018;33(suppl_3):iii35–iii40. doi:10.1093/ndt/gfy175.
11. Uddin MJ, Kim EH, Hannan MA, et al. Nrf2-HO-1 signaling in chronic kidney disease. Antioxidants (Basel). 2021;10(2):258. doi:10.3390/antiox10020258.
12. Ho HJ, Lin CW, Chen MC, et al. Oxidative stress and mitochondrial dysfunction in chronic kidney disease. Cells. 2022;12(1):88. doi:10.3390/cells12010088.
13. Vida C, Oliva C, Yuste C, et al. Oxidative stress in advanced CKD and renal replacement therapy. Antioxidants (Basel). 2021;10(7):1155. doi:10.3390/antiox10071155.
14. Mihai S, Codrici E, Popescu ID, et al. Inflammation-related mechanisms in CKD progression. J Immunol Res. 2018;2018:2180373. doi:10.1155/2018/2180373.
15. Donate-Correa J, Martín-Carro B, Cannata-Andía JB, Mora-Fernández C, Navarro-González JF. Klotho and oxidative stress in kidney disease. Antioxidants (Basel). 2023;12(2):239. doi:10.3390/antiox12020239.
16. Aranda-Rivera AK, Cruz-Gregorio A, Aparicio-Trejo OE, Pedraza-Chaverri J. Nrf2 activation in chronic kidney disease. Antioxidants (Basel). 2022;11(6):1112. doi:10.3390/antiox11061112.
17. Srivastava A, Tomar B, Rath S. Mitochondrial dysfunction and oxidative stress in CKD. Life Sci. 2023;319:121432. doi:10.1016/j.lfs.2023.121432.
18. Lee HE, Park SJ, Kim S, et al. NADPH oxidase inhibitors in diabetic nephropathy. Int J Mol Sci. 2022;23(20):12062. doi:10.3390/ijms232012062.
19. Yan Z, Wang J, Yang G, et al. Biomarkers of progression in chronic kidney disease. Front Med (Lausanne). 2021;8:698305. doi:10.3389/fmed.2021.698305.
20. Qian Q. Inflammation-driven renal injury and CKD progression. Contrib Nephrol. 2017;191:72–83. doi:10.1159/000479257.
21. Tabriziani H, Lipkowitz MS, Vuong N. Chronic kidney disease and oxidative stress. Clin Kidney J. 2018;11(1):130–137. doi:10.1093/ckj/sfx087.
22. Adelusi TI, Du L, Hao M, et al. Keap1/Nrf2/ARE signaling and redox imbalance. Biomed Pharmacother. 2020;124:109746. doi:10.1016/j.biopha.2019.109746.
23. Bondi CD, Manz DH. NRF2 in kidney physiology and disease. Physiol Rep. 2024;12(3):e15961. doi:10.14814/phy2.15961.
24. Redox signalling in chronic kidney disease. Nat Rev Nephrol. 2024;20:101–119. doi:10.1038/s41581-023-00775-0.
25. Piko N, Bevc S, Hojs R, Ekart R. Role of oxidative stress in kidney injury. Antioxidants (Basel). 2023;12(9):1772. doi:10.3390/antiox12091772.
26. García-Caballero C, Martínez-Fernández C, et al. Oxidative stress mechanisms in kidney injury. Free Radic Biol Med. 2024;214:45–58. doi:10.1016/j.freeradbiomed.2024.09.012.
27. Castillo RF, López-González AA, et al. Therapeutic approaches targeting oxidative stress in CKD. Clin Biochem. 2023;117:1–12. doi:10.1016/j.clinbiochem.2023.02.001.
28. Hanaoka H, Kanda E, Iseki K. CKD and inflammatory cytokines. Ren Fail. 2025;47(1):2460267. doi:10.1080/25785826.2025.2460267.
29. Dopierała M, Dzikowska-Diduch O, Domienik-Karłowicz J, et al. Emerging biomarkers in chronic kidney disease. Biomedicines. 2025;13(6):1423. doi:10.3390/biomedicines13061423.
30. Lacerda-Abreu MA, Barreto FC, Barreto DV. Oxidative stress regulation in chronic kidney disease. Antioxidants (Basel). 2025;14(4):461. doi:10.3390/antiox14040461.