Albumin is the most abundant plasma protein in the human body, playing a pivotal role in various physiological functions, including maintaining oncotic pressure, acting as a carrier for numerous substances such as hormones, vitamins, and drugs, and modulating the body's antioxidant and anti-inflammatory responses. Albumin levels are routinely measured in clinical practice as an indicator of nutritional status, liver function, and overall health. The importance of albumin in critical care settings has been well-documented, with numerous studies demonstrating its association with patient outcomes, particularly in intensive care units (ICUs) and among individuals with chronic illnesses, such as nephrotic syndrome.

Serum albumin concentrations are inversely correlated with morbidity and mortality rates in critically ill patients. Low albumin levels can indicate a poor prognosis and are often used as a marker for inflammation, malnutrition, and liver dysfunction. In the ICU, where patients experience a range of acute conditions, monitoring albumin levels allows clinicians to assess the severity of illness and determine appropriate interventions, such as nutritional support and fluid management. Additionally, hypoalbuminemia has been shown to affect the body’s ability to heal and respond to infections, highlighting its importance in patient recovery and survival rates in intensive care settings [1,2].

In nephrology, albumin plays a central role in the management of patients with nephrotic syndrome. Research has shown that low albumin levels in these patients are associated with an increased risk of venous thromboembolism (VTE), further complicating their clinical management. The relationship between albumin levels and VTE in nephrotic syndrome has become a critical point of investigation, as appropriate management of albumin levels can help mitigate this risk [3,4]. Moreover, recent studies have suggested that albumin infusion may be beneficial in treating hypoalbuminemia, although its routine use remains a subject of debate due to concerns regarding its cost-effectiveness and the potential for adverse effects, such as fluid overload or infection [5,6].

Thus, while albumin has long been recognized as a fundamental protein in clinical practice, emerging evidence continues to elucidate its multifaceted role in patient care, particularly in critical and nephrological settings. This paper will explore the clinical implications of albumin, its impact on patient outcomes, and the ongoing research that shapes its application in modern medicine.

This original research study investigates the clinical implications of albumin levels in critically ill patients, with particular focus on its role in intensive care units (ICUs) and nephrology patients. The study assesses the relationship between serum albumin concentrations and patient outcomes, including morbidity, mortality, and the occurrence of complications such as venous thromboembolism (VTE) in nephrotic syndrome patients. The study was conducted in accordance with ethical standards and following the principles of good clinical practice.

Study Design

This study employed a prospective cohort design, where adult patients admitted to an ICU or nephrology clinic were monitored for changes in serum albumin levels and their corresponding clinical outcomes. Data collection occurred over a period of 12 months (March 2024 - March 2025).

Study Setting and Population

The study was conducted at a tertiary care hospital with a specialized ICU and nephrology department. The target population consisted of adult patients (age ≥ 18 years) who were:

• Admitted to the ICU with critical conditions (e.g., sepsis, acute respiratory failure, trauma) or
• Diagnosed with nephrotic syndrome requiring hospitalization.

Patients were enrolled based on the following inclusion criteria:

1. ICU admission or nephrotic syndrome diagnosis confirmed by a healthcare provider.
2. Serum albumin levels measured within 24 hours of admission.
3. Written informed consent from the patient or their legal representative.

Exclusion criteria included:

• Pregnancy or lactation
• Severe hepatic disease or malignancy
• Inability to obtain consent
• Patients under 18 years of age

Intervention

The primary intervention in this study was albumin level monitoring and albumin infusion therapy as clinically indicated. Serum albumin levels were measured on admission and at regular intervals throughout the hospital stay. Patients were categorized into different groups based on their albumin levels:

• Normal albumin group: Serum albumin ≥ 3.5 g/dL
• Low albumin group: Serum albumin < 3.5 g/dL, requiring medical intervention such as albumin infusion

Additionally, patients who exhibited low albumin levels were treated with intravenous albumin as per the clinical protocol in the ICU, which typically involved a dosage of 25 g per day.

Data Collection

The following data were collected for all participants:

1. Demographic Information: Age, gender, comorbidities (e.g., diabetes, hypertension), and primary diagnosis upon admission.
2. Albumin Levels: Serum albumin levels were measured on admission and every 48 hours during the hospital stay.
3. Clinical Outcomes: The primary outcomes were mortality, length of ICU stay, and occurrence of complications such as:

• Venous thromboembolism (VTE), particularly in patients with nephrotic syndrome.
• Infection rates during hospitalization.

4. Treatment: Type of interventions, including albumin infusion therapy and nutritional support.

Data on fluid balance, ventilator-associated pneumonia, and other ICU-related metrics were also collected for correlation with albumin levels.

Outcome Measures

• Primary Outcome: The primary outcome was 30-day mortality, defined as death within 30 days of ICU admission or hospital discharge.
• Secondary Outcomes: These included:
• Length of ICU stay
• Incidence of VTE in nephrotic syndrome patients
• Development of infections or other complications during hospitalization
• Improvement in serum albumin levels after infusion therapy.

Ethical Considerations

The study was approved by the institutional review board (IRB) at the hospital, and all participants provided informed consent or assent as applicable. Patient confidentiality was maintained throughout the study, and data were anonymized prior to analysis.

Statistical Analysis

Descriptive statistics were used to summarize patient demographics, clinical characteristics, and albumin levels. For comparison between groups (normal albumin vs low albumin), chi-square tests and t-tests were used for categorical and continuous variables, respectively. A multivariate regression analysis was performed to evaluate the relationship between serum albumin levels and clinical outcomes, controlling for potential confounders such as age, sex, and comorbid conditions. A Kaplan-Meier survival analysis was conducted to assess the impact of albumin levels on 30-day mortality. Cox proportional hazards models were used to determine the hazard ratio for mortality associated with low albumin levels after adjusting for confounders. Statistical significance was defined as a p-value < 0.05. All statistical analyses were performed using SPSS version 26.

A total of 150 patients were enrolled in the study, with 75 patients in the low albumin group (serum albumin < 3.5 g/dL) and 75 patients in the normal albumin group (serum albumin ≥ 3.5 g/dL). Among these, 87 patients were admitted to the ICU with critical conditions such as sepsis, acute respiratory failure, and trauma, while 63 patients were diagnosed with nephrotic syndrome.

Baseline Characteristics

The baseline demographic and clinical characteristics of the study population are summarized in Table 1. No significant differences were observed between the two groups in terms of age, sex, and comorbid conditions such as diabetes and hypertension. However, the low albumin group had a significantly higher proportion of patients with severe infections (27% vs. 13%, p = 0.02) and a higher percentage of patients with advanced stages of nephrotic syndrome (p = 0.03), reflecting the more severe clinical condition associated with hypoalbuminemia. Additionally, the low albumin group had a higher prevalence of liver disease (20% vs. 13%, p = 0.04).

Albumin Levels and Clinical Outcomes

The mean serum albumin level on admission was significantly lower in the low albumin group (2.1 ± 0.5 g/dL) compared to the normal albumin group (3.8 ± 0.4 g/dL, p < 0.001). Following albumin infusion, the serum albumin levels in the low albumin group improved to 3.1 ± 0.6 g/dL by the end of the study (p < 0.001), demonstrating the effectiveness of the intervention in restoring albumin levels.

Mortality

The 30-day mortality rate was significantly higher in the low albumin group at 32% compared to 18% in the normal albumin group (p = 0.03). Multivariate regression analysis revealed that low albumin levels were independently associated with an increased risk of mortality (adjusted hazard ratio = 2.3, 95% CI: 1.1–4.9), underscoring the clinical significance of serum albumin as a prognostic marker in critically ill patients.

ICU Stay

The mean ICU stay was significantly longer in the low albumin group (10 ± 3 days) compared to the normal albumin group (6 ± 2 days, p = 0.01). This extended length of stay reflects the more complex clinical status of patients with hypoalbuminemia, who often require more intensive care and monitoring.

Complications and Secondary Outcomes

Venous Thromboembolism (VTE)

In the subgroup of patients with nephrotic syndrome, the incidence of venous thromboembolism (VTE) was significantly higher in the low albumin group (10%) compared to the normal albumin group (2%, p = 0.04). This finding supports the hypothesis that low serum albumin levels contribute to a higher risk of thromboembolic events, particularly in nephrotic syndrome patients who are already at risk for such complications.

Infection Rate

The infection rate was higher in the low albumin group (27%) compared to the normal albumin group (15%, p = 0.02). This is consistent with previous research suggesting that hypoalbuminemia impairs immune function, making patients more susceptible to infections during hospitalization.

Statistical Analysis

Kaplan-Meier survival analysis demonstrated that patients in the low albumin group had significantly lower survival rates at 30 days compared to the normal albumin group (p = 0.03). The Cox proportional hazards model further confirmed that low albumin levels were an independent predictor of 30-day mortality, with a hazard ratio of 2.3 (95% CI: 1.1–4.9).

Statistical tests (t-test) showed that the mortality rate was significantly different between the two groups (p = 0.03), as was the ICU stay duration (p = 0.01).

Additional Outcomes

In terms of albumin therapy, 31% of patients in the low albumin group who received albumin infusion demonstrated significant clinical improvement, including reduced fluid retention and enhanced respiratory function, compared to 15% in the normal albumin group (p = 0.05). These findings highlight the potential therapeutic benefit of albumin infusion in critically ill patients with hypoalbuminemia.

Statistical Tables and Graphs

Table 1: Baseline Characteristics of Study Population

The bar chart below compares the mortality rates between the low and normal albumin groups. The mortality rate was significantly higher in the low albumin group (32%) compared to the normal albumin group (18%), with a p-value of 0.03.

The bar chart compares the ICU stay durations between the two groups. The low albumin group had a significantly longer ICU stay (10 days) compared to the normal albumin group (6 days), with a p-value of 0.01.

This study aimed to explore the relationship between serum albumin levels and patient outcomes in critically ill individuals. The results underscore the significant impact of hypoalbuminemia on morbidity, mortality, and complications such as venous thromboembolism (VTE) and infections. These findings are consistent with previous research highlighting the clinical importance of albumin as a marker of illness severity and a therapeutic target in critical care.

Clinical Significance of Albumin in Critical Illness

Albumin plays a crucial role in maintaining oncotic pressure and regulating fluid balance. In critically ill patients, low serum albumin levels are associated with poor prognosis, including increased mortality and extended hospital stays. Our results show that patients with low albumin levels had a 32% mortality rate, significantly higher than the 18% seen in the normal albumin group (p = 0.03). This aligns with studies demonstrating that hypoalbuminemia is a strong predictor of adverse outcomes in ICU settings [7]. Low albumin levels are often indicative of systemic inflammation, malnutrition, or liver dysfunction, each of which can exacerbate the severity of illness. In agreement with Sundaravadivazhagan et al., who found that low albumin levels were independently associated with increased mortality in critically ill patients, our study reinforces the need for close monitoring of albumin levels in the ICU [8].

Albumin as a Marker for Infection and Immune Function

In this study, patients in the low albumin group had a higher incidence of infections (27%) compared to the normal albumin group (15%, p = 0.02). This finding is consistent with the established understanding that hypoalbuminemia impairs immune function, making patients more susceptible to infections. Gyamlani et al. suggested that albumin's role in modulating inflammation and immune responses is crucial in preventing infections during critical illness [9]. Our findings add to this body of evidence, indicating that low albumin levels may contribute to higher infection rates and poorer recovery in ICU patients. As such, albumin supplementation may be considered to improve immune function, although the cost-effectiveness of such interventions remains a subject of debate [10].

Venous Thromboembolism and Hypoalbuminemia

One of the novel findings in our study was the association between low albumin levels and an increased incidence of venous thromboembolism (VTE) in patients with nephrotic syndrome. In this cohort, 10% of patients in the low albumin group developed VTE, compared to just 2% in the normal albumin group (p = 0.04). These results are consistent with studies by Kovesdy et al., who demonstrated that hypoalbuminemia is an independent risk factor for thromboembolic events in nephrotic syndrome patients [11]. The mechanisms by which hypoalbuminemia predisposes individuals to VTE are complex, involving both endothelial dysfunction and hypercoagulability. Low albumin levels may lead to changes in the coagulation cascade, promoting thrombus formation. This highlights the importance of managing albumin levels in nephrotic syndrome and other high-risk populations to prevent thromboembolic complications.

ICU Stay and Resource Utilization

The study also found that the low albumin group had a significantly longer ICU stay (10 days) compared to the normal albumin group (6 days, p = 0.01). This is in line with findings from Molnar et al., who reported that low albumin levels are associated with prolonged hospitalization and increased resource utilization in critical care settings [12]. The extended ICU stays observed in patients with low albumin levels likely reflect both the severity of their underlying conditions and the complications associated with hypoalbuminemia, such as infections and fluid imbalances. These patients may require more intensive care and longer recovery periods, further highlighting the need for timely albumin monitoring and intervention in critical settings.

Albumin Infusion and Clinical Improvement

A key aspect of this study was the albumin infusion therapy administered to patients in the low albumin group. Following albumin supplementation, 31% of patients showed significant clinical improvement, including reduced fluid retention and enhanced respiratory function. This therapeutic effect is consistent with the findings of Jolly et al., who suggested that albumin infusion can provide benefits in hypoalbuminemic patients by restoring fluid balance and improving clinical outcomes [13]. However, despite the observed benefits, the high cost of albumin therapy remains a significant challenge. Future studies should focus on evaluating the cost-effectiveness of albumin infusion in various patient populations, particularly in the context of critical care where its use is most prevalent.

Limitations and Future Directions

While this study provides valuable insights into the role of albumin in critical care, it is not without limitations. The study design was observational, which limits the ability to establish causality between low albumin levels and patient outcomes. Additionally, the relatively small sample size and single-center design may limit the generalizability of the findings. Future multicenter, randomized controlled trials are needed to confirm these results and further explore the potential therapeutic benefits of albumin infusion in critical illness.

Moreover, the potential adverse effects of albumin therapy, including fluid overload and infection risk, warrant further investigation. Prospective trials that examine the optimal dosage, duration, and timing of albumin infusion will be crucial in developing evidence-based guidelines for its use in critical care settings.

This study highlights the critical role of serum albumin as both a prognostic marker and a therapeutic target in critically ill patients. Low albumin levels are strongly associated with increased mortality, prolonged ICU stays, and higher incidence of complications such as infections and venous thromboembolism. Albumin infusion therapy demonstrated clinical benefits, including improved fluid balance and enhanced patient recovery. Given its clinical significance, regular monitoring and timely intervention for hypoalbuminemia should be considered essential in critical care settings. Future research should focus on optimizing albumin therapy and evaluating its cost-effectiveness across diverse patient populations.

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