Use of Total Protein and Hemoglobin for Evaluating Nutritional Status in Patients Undergoing Hemodialysis: A Multi-Center Experience

Malnutrition is one of the most common complications in
patients undergoing maintenance hemodialysis...


Introduction
Malnutrition is one of the most common complications in patients undergoing maintenance hemodialysis (HD) [1] and is an independent risk factor for mortality in these patients [2][3][4].
Past research [5][6][7] has found that malnutrition was positively correlated with cardiovascular events, which are leading causes of death in patients undergoing HD. Because nutritional status is so vital to these patients, the concept of Protein-Energy Wasting (PEW) is an increasing area of focus for practitioners who treat patients with end-stage renal disease (ESRD). PEW is mainly caused by inadequate energy intake, aggravated by ESRD itself and nutrient consumption during dialysis. Clinically, malnutrition is characterized by low BMI, low serum ALB, micro-inflammation, renal anemia, and amyotrophy. The lower the serum ALB level, the higher the likelihood of developing pulmonary hypertension, which significantly impacts survival [8]. Reduced serum ALB levels independently predicted mortality in patients undergoing HD [9].
Low serum UA was considered a mortality risk factor for patients with many comorbidities and hypoalbuminemia [10].
The relationship of other biomarkers to the nutritional status of patients undergoing HD, such as total protein (TP) and hemoglobin (HGB), have not been fully explored, and the relationship of these biomarkers to prognosis is unknown. The findings of recent nutrition biomarker studies of patients undergoing HD were limited by methodological issues such as a small sample size and single center data. Thus, studies with larger cohorts of patients undergoing HD are needed. Consequently, the aims of this study were to determine the nutritional status of patients undergoing HD and to explore predictors of malnutrition in these patients.

Study Design and Participants
This was a cross-sectional, retrospective, observational nutritional investigation of patients receiving HD for at least three months at the time of enrollment. All patients received routine measurements of biochemical indicators as standard-of-care. We excluded patients with limited life expectancy due to cachexia, malignancies, decompensation-stage hepatopathy, and those who developed acute inflammation during the study. All patients' demographic characteristics and clinical information were collected,

Hemodialysis
All patients underwent two to three HD sessions per week, with a session length of 3.5 to 4.0 hours. Duration of treatment was individualized according to the urea kinetics model. During the HD sessions, blood flow was 250-300 mL/min, and the dialysate flow was 500 mL/min. The buffer that was used was bicarbonate, at a concentration of 35 mmol/L. The glucose concentration of the dialysate was 100 mg/dL. The HD machines were of the proportion type with a controlled ultrafiltration module, and water treatment was performed using reverse osmosis.

Statistical Analysis
Data are expressed as the mean + standard deviation for continuous variables and as percentages for categorical variables.

Patients' Baseline Characteristics
We enrolled 596 patients undergoing HD in this study. Baseline characteristics are shown in Table 1. There were 353 (59.2%) males and 243 (40.8%) females. Their mean age was 57.1±14.1 years, and the mean duration of HD was 50.6±34.7 months.
Patients were divided into a malnutrition group (ALB >35 g/L; n=493, 82.7%) and a normal nutrition group (ALB <35 g/L; n=103 patients, 17.3% ). TP, HGB, Cr, and HDL were significantly higher in the normal nutrition group than in the malnutrition group. In contrast, there were no significant between-group differences in UA, BUN, TG, CHOL, LDL, and BMI. Interestingly, the two groups had nearly identical mean BMI, reminding us that BMI may not be a meaningful index of nutritional status for certain patients receiving HD, as shown in Table 2.

Correlation Analysis of ALB and Other Biochemical Indicators
Correlation analysis was carried out to compare the "gold standard" ALB with another biochemical indicators. As shown in Table 3

ROC Analysis to Determine the Appropriate Biochemical Indicators for Evaluating Malnutrition in Patients Undergoing HD
During ROC analysis, we used ALB as the "gold standard" to determine suitable biochemical indicators for malnutrition.
The ROC curves for the variables with significant between-group differences between the normal and malnutrition groups are shown in

Discussion
Malnutrition is a common complication in patients undergoing HD, and it is an independent risk factor for cardiovascular events [7,11]. Also, malnutrition and reduced ALB levels are known independent predictors of mortality in patients receiving HD [3,9]. Physicians must examine the nutritional status of patients undergoing HD early in the disease. Some studies have shown that nutrition interventions significantly improved physical functioning, quality of life, and survival in patients with malnutrition [12,13].
Nutritional evaluations for patients undergoing HD include subjective global assessment (SGA) and malnutrition-inflammation scores (MIS). SGA [14] is a valid nutritional marker for patients with ESRD [15] and an independent predictor of mortality for patients receiving HD [9]. MIS [16] includes subjective nutritional evaluation and objective indices, and are applicable to patients receiving HD [17,18]. However, because of the complexity of these techniques, they have limited use in clinical practice. Additionally, many hospitals lack professional nutritionists who would normally implement such methods.
Objective and common indicators for evaluating the nutrition status of patients undergoing HD, particularly early on, are important. Physicians should therefore attend to patients' nutritional status and implement nutrition interventions when indicated. ALB, a traditional nutritional marker, is used as a predictive biomarker in various fields [9,[19][20][21]. These include nutritional evaluation in patients with diseases that produce edematous symptoms [22]. ALB is therefore useful for evaluating nutritional status in patients undergoing HD. In addition, ALB can be compared to other nutrition-related biochemical indicators.
Previous research has supported the usefulness of TP and HGB as potential malnutrition biomarkers in certain patients, such as those who are status-post total joint replacement, elderly patients, and others [23][24][25] [27,28]. The authors concluded that Cr levels might provide additional information regarding nutritional status in patients undergoing HD [29]. Future, well-powered studies are needed to determine the Cr threshold with prognostic value for nutritional assessments.
In conclusion, we examined the usefulness of ALB, TP, and HGB for evaluating malnutrition in patients undergoing HD. Our results may provide additional information for detecting and treating malnutrition in this population.

Supplementary Material
No supplementary material.