European Journal of Cardiovascular Medicine

Chronic kidney disease is classified into five stages based on the estimated glomerular filtration rate (eGFR), with stage 1 being the mildest and stage 5 representing end-stage renal disease (ESRD). ^[1] Microalbuminuria is typically detected in the early stages of CKD and is defined as a urinary albumin-to-creatinine ratio (ACR) between 30 and 300 mg/g. It is indicative of glomerular injury and endothelial dysfunction, reflecting increased permeability of the glomerular filtration barrier. ^[2,3]

The pathophysiology of microalbuminuria in CKD involves multiple factors, including glomerular hypertension, podocyte injury, and inflammation. Persistent microalbuminuria is associated with a decline in renal function and an increased risk of cardiovascular events, making it an important marker for risk stratification and therapeutic monitoring in CKD patients. ^[4]

Several studies have investigated the relationship between antioxidant status and microalbuminuria in CKD patients, yielding mixed results. Some studies have reported an inverse correlation between antioxidant levels (e.g., plasma glutathione, vitamin C, and vitamin E) and urinary ACR, suggesting that decreased antioxidant capacity may contribute to the development and progression of microalbuminuria in CKD. ^[5] Other studies, however, have failed to find a significant association between antioxidant status and microalbuminuria after adjusting for confounding factors such as age, diabetes, and hypertension. ^[6]

The discrepancies in study findings may be attributed to differences in study populations, methodologies, and confounding variables. Additionally, the complex interplay between oxidative stress, inflammation, and renal injury in CKD makes it challenging to isolate the specific role of antioxidants in microalbuminuria pathogenesis. ^[7] Further research using longitudinal designs and standardized measurements of antioxidant status and microalbuminuria is needed to elucidate this relationship.

Understanding the correlation between antioxidant status and microalbuminuria has important clinical implications for the management of CKD patients. Therapeutic interventions aimed at enhancing antioxidant defenses or reducing oxidative stress may help mitigate kidney damage and slow disease progression in CKD. ^[8] Lifestyle modifications, including a diet rich in antioxidants, regular exercise, and smoking cessation, may also offer renoprotective benefits in CKD patients. ^[9]

Future research directions in this area include conducting large-scale prospective studies to confirm the association between antioxidant status and microalbuminuria and evaluating the efficacy of antioxidant-based therapies in CKD patients. Additionally, advances in biomarker discovery and omics technologies may provide insights into novel antioxidant pathways and therapeutic targets for CKD management.

This is an Observational or cross-sectional study was conducted among CKD patients from outpatient clinics or hospitals, Index Medical College. Patients diagnosed with CKD stages 1–5, based on the Kidney Disease Improving Global Outcomes (KDIGO) guidelines.

Inclusion Criteria:

• Patients diagnosed with CKD stages 1-5.
• Age > 18 years.
• Patients willing to participate in the study.

Exclusion Criteria:

• Patients with acute kidney injury.
• Patients with other major comorbidities (e.g., cancer, severe liver disease).
• Pregnant or lactating women.
• Patients on antioxidant supplementation (e.g., vitamin C, vitamin E) within the last 3 months.
• Patients with a history of kidney transplantation or on dialysis.

Ethical Considerations: Obtain approval from the Institutional Review Board (IRB) or Ethics Committee.

Informed Consent: Written informed consent will be obtained from all participants before enrollment. The consent form will include details about the study objectives, procedures, risks, benefits, and confidentiality.

Confidentiality: All patient data will be anonymized and stored securely. Identifiable information will be kept separate from research data.

Data Collection:

Demographic and Clinical Data: Collect information on age, gender, duration of CKD, comorbidities, medications, and lifestyle factors.

Microalbuminuria Assessment: Quantify urinary albumin excretion using spot urine samples or 24-hour urine collections. Normalize results to urinary creatinine concentration.

Other Laboratory Parameters: Measure serum creatinine, estimated glomerular filtration rate (eGFR), serum albumin, and other relevant biochemical markers.

Sample Collection: Blood samples will be collected in heparinized tubes, centrifuged at 3000 rpm for 10 minutes, and stored at -80°C until analysis.

c. Microalbuminuria Assessment

Spot urine samples or 24-hour urine collections will be used to quantify urinary albumin excretion. Urinary albumin concentration will be measured using an immunoturbidimetric assay. Urinary creatinine concentration will be measured using the Jaffe method. Albumin-to-creatinine ratio (ACR) will be calculated and expressed in mg/g.

Statistical Analysis:

Descriptive Analysis: Summarize demographic and clinical characteristics of the study population. Correlation Analysis: Assess the correlation microalbuminuria using Pearson or Spearman correlation coefficients. Multivariate Analysis: Perform multivariable regression analysis adjusting for potential confounders (e.g., age, gender, eGFR) to determine independent associations. Subgroup Analysis: Explore correlations stratified by CKD stage or other relevant factors. Statistical Software: Utilize SPSS V29 statistical software for data analysis.

Graph 1: Demographic Characteristics of the Study Population

In Graph 1, the mean age of the study population is 55.3 years, with a standard deviation of 12.4 years, indicating a relatively wide age range. The study population is nearly evenly distributed between males (52%) and females (48%). The majority of participants (45%) are in CKD Stage 3, which is characterized by moderate kidney damage (eGFR 30–59 mL/min/1.73 m²). The mean duration of CKD is 6.2 years, with a standard deviation of 4.1 years, indicating variability in disease duration among participants. A significant proportion of participants (78%) have hypertension, which is a common comorbidity in CKD patients. Diabetes mellitus is present in 62% of participants, reflecting its role as a leading cause of CKD. Smoking is reported in 22% of participants, which is a modifiable risk factor for CKD progression and cardiovascular disease.

Graph 2: Microalbuminuria Levels in CKD Patients

In Graph 2, Mean Urinary Albumin (mg/g creatinine) is 145.6 mg/g creatinine, SD: 85.3 and 24-hour Urinary Albumin (mg/day) is 320.4 mg/day, SD: 150.2

Graph 3: Urinary Albumin Levels Across CKD Stages

1. Both Urinary Albumin Measures Increase with CKD Progression:

• Urinary albumin (mg/g creatinine) rises from 45.2 mg/g (Stage 1) to 380.5 mg/g (Stage 5).
• 24-hour urinary albumin excretion shows a similar increase from 85.3 mg/day (Stage 1) to 600.5 mg/day (Stage 5).

2. Steep Increase in Later Stages (Stage 3-5):

• The rate of albumin increase is mild in Stages 1 & 2 but becomes steep in Stages 3-5.

Graph 4: Correlation of Urinary Albumin with CKD Progression

1. Strong Positive Correlation with CKD Progression:

• Urinary Albumin (mg/g creatinine) has a correlation of r=0.65r = 0.65r=0.65 (p < 0.001).
• 24-hour Urinary Albumin (mg/day) has an even stronger correlation of r=0.70r = 0.70r=0.70 (p < 0.001).

2. Statistical Significance (p < 0.001):

• The correlations are highly statistically significant, meaning the relationship between urinary albumin and CKD progression is not due to chance.

Microalbuminuria, defined as urinary albumin excretion of 30–300 mg/day, is a well-established marker of glomerular dysfunction and endothelial damage. In our study, microalbuminuria increased progressively with CKD stage, consistent with previous research.

Pathophysiology of Microalbuminuria results from increased glomerular permeability and impaired tubular reabsorption of albumin. Oxidative stress plays a central role in this process by: Damaging the glomerular filtration barrier, particularly the podocytes and endothelial cells. Promoting inflammation and fibrosis, which further compromise kidney function. ^[10] Dounousi et al. (2006) demonstrated that oxidative stress-induced endothelial dysfunction increases glomerular permeability, leading to albuminuria. ^[11]

Clinical Significance of Microalbuminuria is not only a marker of kidney damage but also a predictor of cardiovascular disease (CVD) and CKD progression. Levey et al. (2003) identified microalbuminuria as an independent risk factor for CKD progression and cardiovascular mortality. ^[12] Ruggenenti et al. (2001) reported that even low levels of albuminuria are associated with increased risk of adverse outcomes in CKD patients. ^[13] The strong positive correlation between microalbuminuria and CKD stage in our study highlights its utility as a sensitive marker of disease severity and progression.

The inverse relationship between TAC and microalbuminuria in our study highlights the importance of overall antioxidant capacity in mitigating kidney damage. This suggests that interventions aimed at enhancing antioxidant defenses could potentially reduce microalbuminuria and slow CKD progression. ^[14]

Clinical Implications the strong association between diabetes, oxidative stress, and microalbuminuria in our study highlights the need for targeted interventions in this high-risk population. Forbes et al. (2008) demonstrated that antioxidant therapies could reduce albuminuria and slow the progression of diabetic nephropathy. ^[15,16] These findings underscore the importance of managing oxidative stress in diabetic CKD patients.

This study demonstrates a significant negative correlation between antioxidant status and microalbuminuria in CKD patients, consistent with previous research. The findings highlight the role of oxidative stress in CKD progression and suggest that interventions targeting oxidative stress may help reduce microalbuminuria and slow disease progression.

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