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PhilSPEN Online Journal of Parenteral and Enteral Nutrition

(Article 25 | POJ_0019.html) Issue February 2012 - December 2014: 89-104

Original Clinical Investigation

Impact of nutritional status on mortality in maintenance hemodialysis patients in a private tertiary care hospital in the Philippines

Abstract | Introduction | Methodology | Results | Discussion | Conclusion | References | PDF (555 KB) |Back to Articles Page

Submitted: July 10, 2014 | Posted: October 4, 2014

AUTHORS:

Christian S. Bernardo MD (2), Divina Cristy Redondo-Samin MD (1)*, Teodora Wanasen MD (1)

*Corresponding Author (dcsredondo@yahoo.com)

INSTITUTION WHERE RESEARCH WAS CONDUCTED:

  1. Medical Nutrition and Weight Management Center, Premiere Medical Center, Nueva Ecija, Philippines
  2. Department of Internal Medicine, Premiere Medical Center, Nueva Ecija Philippines

ABSTRACT: | Back

Background: Malnutrition is prevalent among dialysis patients and a strong association exists between poor nutritional status and morbidity and mortality in patients with end-stage renal disease who are treated with hemodialysis.

Objective: This study was conducted to determine the association of nutritional status indicators with mortality in maintenance hemodialysis patients .

Methodology: This is a retrospective cohort study where twenty-nine patients who started maintenance hemodialysis in a provincial tertiary hospital between May 2010 and October 2012 were included. Nutritional status indicators like modified subjective global assessment, body mass index, serum creatinine, lymphocyte count, skin fold thickness, mid-arm circumference, mid-arm muscle circumference were analyzed. Baseline and two-year follow-up measurements were done. Cox proportional hazards analysis was used to determine the association of nutritional status indicators with mortality. Fisher`s exact test was performed whenever data was sparse. Pearson correlation analysis was utilized to determine the correlation between nutritional status indicators and the number of OPD and hospital visits.

Results: Fifty percent of patients with below normal baseline nutritional status died within the study period. Increasing body mass is correlated with decreased mortality. Relatively “lower” creatinine levels had higher mortality rates. Patients’ nutritional status decreased within the two-year study period. Below normal mid-arm circumference (MAC) measurements and mid-arm muscle circumference (MAMC) were observed to have higher mortality rates. In the two-year follow-up, no one expired among patients with normal baseline nutritional status based on the modified SGA scoring.  Baseline blood creatinine level of more than 10mg/dL was associated with decreased risk of mortality.

Conclusion: Nutritional status in hemodialysis patients is directly associated with mortality and renal function status.

Recommendation: Early assessment of the nutritional status of dialysis patients is recommended to prevent development or progression of malnutrition and to decrease the mortality risk among chronic hemodialysis patients.

 

KEYWORDS: hemodialysis, nutritional status, mortality, SGA, malnutrition

 

INTRODUCTION | Back

Several nutritional problems are common among patients with end-stage renal disease (ESRD) as described in a Dialysis Outcomes Quality Initiative (DOQI) (1). Due to the kidney’s unique role in nutrient metabolism and the nature of disease progression, patients with renal failure are uniquely susceptible to malnutrition. Patients in beginning dialysis have a high incidence rate of malnutrition because their disease has progressed over time till the end stage organ failure (2). Studies have showed patients undergoing maintenance hemodialysis (MHD) are wasted or malnourished (3,4).

A strong association exists between nutritional status and morbidity and mortality in patients with end-stage renal disease who are treated with hemodialysis (5). Protein energy malnutrition (PEM) is a strong predictor of mortality in maintenance hemodialysis (MHD) patients (6).  The mortality risks associated with several readily measured nutritional indictors were evaluated, including modified subjective global assessment, body mass  index (BMI), serum albumin, serum creatinine, normalized protein catabolic rate (nPCR), and lymphocyte count. These several readily measured nutritional indicators predict mortality among hemodialysis patients and that changes in these indicator values over 6 months promote additional important prognostic information (7). Large sets of data suggest serum albumin, serum creatinine, and BMI are independently associated with survival (8). Moreover, data from the USRDS using the serum albumin and BMI confirm these findings (5). Recent findings on the predictive value of anthropometrics parameters on mortality of hemodialysis patients showed that percentage of body fat, mid-arm circumference (MAC), mid-arm muscle circumference (MAMC) and triceps skinfold thickness (TSF) were independent predictors of mortality of haemodialysis patients, and MAC was the most predictive one (9).

Since PEM is a common factor influencing morbidity and mortality of hemodialysis patients, assessing their nutritional status is important. Many other methods are available for the assessment of nutritional status of hemodialysis patient (10), but only one nutrition assessment tool, the modified SGA nutrition assessment, is being used in the Philippines (11).  The first prospective observational study done in this institution in which the MHD patients were nutritionally assessed by modified SGA dialysis malnutrition score, food intake recall and anthropometry showed that 45% have moderate malnutrition and 36% have severe malnutrition (12). Another study done in Metro-Manila using the PhilSPEN modified SGA showed a prevalence of malnutrition of 77% with 57% having severe malnutrition (13). The aim of this study was to determine association of the nutritional status indicators with mortality of patients on maintenance hemodialysis.

 

METHODOLOGY | Back

Patients

This is a retrospective cohort study of 29 adult patients purposively  selected from the outpatient hemodialysis center at Premiere Medical Center. They were part in hospital malnutrition prevalence study among hemodialysis patients previously conducted (12). Hospital administration and informed consent to participate were obtained. The inclusion criteria were: age above 18 years old and those patients nutritionally assessed within the 2010 PMC Malnutrition Prevalence Study among maintenance hemodialysis patients. The exclusion criteria were: 1) elective living donor kidney transplant within six months; 2) moved from the study center to another dialysis center within 2 years; 3) positive hepatitis B or HIV serology; or 4) failure to sign the informed consent form.

Data Collection

The patients’ charts were reviewed and data were collected for several nutritional indicators including BMI, serum albumin, serum creatinine,  lymphocyte count, and modified SGA. Baseline measurements were made during the year the patients entered from the previous prevalence study (May 10 to October 2010) and involved clinical, anthropometrical and laboratory examinations. After that, the patients were monitored after two years (September 2012) in the same manner. Anthropometric measurements and nutrition assessment using the modified SGA (modified SGA study) were done by the same nutrition nurse and dietitians in the prevalence study.
 
Nutritional Assessment

The nutritional status of the patients was assessed by the modified Subjective Global Assessment technique (Dialysis Malnutrition Scoring Tool) (14). Patients were re-evaluated within two years from their initial nutrition assessment. For the purpose of statistical analysis, patients were divided into two groups: normal or well nourished, undernourished (this included moderately or suspected malnutrition) and the severely malnourished, as defined by modified Subjective Global Assessment.

 

Outcome Variables

The primary outcome was   death while secondary outcomes include number of OPD visits and current nutritional status of survivors. We censored patients at the time of living (18) or deceased (10) at  the  end of the study observation period on November 30, 2012.

Data Analysis

Descriptive analysis involved the determination of summary statistics such as the mean, range and standard deviation for quantitative variables (e.g. age) and the frequency and percentage distribution of qualitative variables (e.g. sex). The point and 95% confidence interval (CI) estimates of the mortality rate of the patients were also derived. Cox proportional hazards analysis was used to determine the crude association of baseline demographic, anthropometric, nutritional, and biochemical parameters with mortality. Whenever data was sparse, the variables were dichotomized and Fisher’s exact test was performed. Meanwhile, Pearson correlation analysis was performed to determine the correlation between the baseline anthropometric, nutritional and parameters revealed that the modified SGA score and the number of  hospital visits. A 5% level of significance was used to test the hypothesis that there is a significant correlation between two variables. Stata version 12 was used in the said computations.


RESULTS | Back

Patient Profile

Twenty-nine (29) patients undergoing hemodialysis were enrolled into the study and followed up after two years to determine mortality. At baseline, the mean age of the said patients was 52.10 years with a standard deviation of 15.38 years. Furthermore, the oldest and youngest patients were aged 22 and 83 years, respectively. 58.62% or 17 out of 29 of these patients are males. Table 1 presents the age and sex distribution of the patients.

By demographic characteristics, females had a slightly higher risk of mortality than males in the two-year study period (HR: 1.46; 95% CI: 0.42, 5.02). However, the association between gender and mortality was not statistically significant (p=0.553). Meanwhile, patients aged 40 to 59 years were almost 4.38 times more at risk of mortality compared to the patients aged 22 to 39 years. In contrast, patients aged 60 to 83 years were ten percent (10%) less likely to expire within the study period compared to the patients aged 22 to 39 years. The association between age and mortality was not statistically significant (p>0.05).

tbl01_bernardo

Anthropometric Measurements

At baseline, the mean pre-hemodialysis weight of the patients was 55.69 kg with a standard deviation of 11.00 kg and a range of 37.5 to 80.5 kg. Meanwhile, the mean post-hemodialysis of the patients was 53.62 kg with a standard deviation of 10.78 kg and a range of 35.5 to 75.5 kg. Based on the post-hemodialysis weight of the patients, the mean BMI was computed at 20.50 kg/m2 with a standard deviation of 3.15 kg/m2 and a range of 14.4 to 28.4 kg/m2. Using the WHO BMI classification, it was found that 72.41% (21 out of 29) of the patients had normal BMI, while 24.14% (7 out of 29) were underweight and one patient was overweight. Patients who are underweight had almost the same risk of mortality compared to the patients with normal BMI. Table 2 shows the cross-tabulation of patients by nutritional status and BMI classification.

tbl2_bernardo

At baseline, the mean TSF measurement of the patients was 11.55mm with a standard deviation of 3.02mm and a range of 6.3 to 17.67mm. Based on the TSF classification, 24.14% (7 out of 29) of the patients had normal measurements, while the remaining had below normal measurements that ranged from mild (10.34% or 3 out of 29) to severe (13.79% or 4 out of 29) malnutrition. Table 3 shows the cross-tabulation of patients by nutritional status and TSF classification.

tbl3_bernardo

At baseline, the mean MAC measurement of the patients was 22.47cm with a standard deviation of 4.26cm and a range of 14.33 to 29.8cm. Based on the MAC classification, only two (6.90%) patients had normal measurements while the others were classified as having mild (20.69% or 6 out of 29), moderate (58.62% or 17 out of 29), or severe (13.79% or 4 out of 29). Table 4 shows the cross-tabulation of patients by nutritional status and MAC classification.

tbl4_bernardo

At baseline, the mean MAMC measurement of the patients was 18.48cm with a standard deviation of 4.35cm and a range of 5.55 to 25.78cm. Based on the MAMC classification, only one patient had normal measurements while the others were classified as having mild (17.24% or 5 out of 29), moderate (62.07% or 18 out of 29), or severe (17.24% or 5 out of 29). Table 5 shows the cross-tabulation of patients by nutritional status and MAMC classification.

tbl5_bernardo

The patients who had below normal baseline TSF measurements were thirty-five percent (35%) less likely to expire compared to the patients who had normal TSF measurements. Nevertheless, the association between TSF measurement and mortality was not statistically significant (p=0.531). The patients with below normal baseline MAC measurements were almost two times more at risk of mortality compared to patients who had normal MAC measurements. However, the association between MAC measurement and mortality was not statistically significant (p=0.481). Similarly, the patients with below normal baseline MAMC measurements were almost three times more at risk of mortality compared to patients who had normal MAMC measurements. Nonetheless, the association between MAMC measurement and mortality was not statistically significant (p=0.338).

Co-Morbidities

At baseline, the most common co-morbidity among the patients is Type 2 diabetes (55.17% or 16 out of 29) followed by CAD (51.72% or 15 out of 29) and hypertension (0.34% or 3 out of 29), respectively. Figure 1 depicts the co-morbidities experienced by these hemodialysis patients.

fig1_bernardo

Hemodialysis

The mean length of hemodialysis treatment of the patients was 20.31 months with a standard deviation of 23.65 months and a range of 1 to 108 months. Majority (89.66% or 26 out of 29) of the patients undergoes hemodialysis treatment twice a week while the rest either have hemodialysis once or thrice a week. Twenty-five (25) out of the patients had information regarding hemodialysis adequacy as expressed by kt/V. The mean hemodialysis adequacy score of these patients was 1.48 kt/V with a standard deviation of 0.35 kt/V. The lowest and highest hemodialysis adequacy scores were 0.54 and 1.97 kt/V, respectively. As per the guidelines [40], the kt/V of 1.2 is the standard for dialysis adequacy. Hence, 88% (22 out of 25) of the said patients had adequate hemodialysis treatment. Lastly, compliance to prescribed hemodialysis treatment was also ascertained and it was found that 75.86% or 22 out of 29 were compliant to hemodialysis.

Nutrient Intake
At baseline, the mean daily caloric intake of the patients was 1204.69 calories with a standard deviation of 291.40 calories. Meanwhile, the mean daily protein intake of these patients was 52.06 grams with a standard deviation of 20.01 grams. This translated to a mean modified SGA score of 13.14 points with a standard deviation of 4.25 points and a range of 7 to 23 points. Based on the said scores, 68.97% (20 out of 29) of the patients had below normal nutritional status. Lastly, it was noted that loss of appetite was experienced by 24.14% (7 out of 29) of the patients while on hemodialysis. Figure 2 depicts the distrubution of patients by loss of appetite and nutritional status.

fig2_bernardo

Biochemistry
                 
Creatinine

At baseline, the mean blood creatine level of the patients was 11.74 mg/dL with a standard deviation of 4.49 mg/dL and a range of 3.63 to 19.6 mg/dL. Based on the cut-offs for the normal blood creatinine values, which ranges from 0.6 to 1.3 mg/dL for males and from 0.6 to 1.0 mg/dL for females, all the patients had above normal blood creatinine levels.

Patients who had blood creatinine levels between 5.01 to 10.00 mg/dL were 67% less likely to expire compared to the patients who had creatinine levels between 3.63 to 5.00 mg/dL. Furthermore, the patients who had blood creatinine levels between 10.01 to 15.00 mg/dL were 87% less likely to expire compared to the patients who had blood creatinine levels between 3.63 to 5.00 mg/dL. Lastly, the patients who had blood creatinine levels between 15.01 to 19.60 mg/dL were 76% less likely to expire compared to the patients who had blood creatinine levels between 3.63 to 5.00 mg/dL. Result of the survival analysis showed that having a baseline blood creatinine level of 10.01 to 15.01 mg/dL was statistically associated with decreased risk of mortality (p=0.046).

At end point, the mean creatinine level of the eighteen (18) patients who survived was 13.59 mg/dL with a standard deviation of 4.03 mg/dL and a range of 5.6 to 19.8 mg/dL. Using the paired t-test, it was shown that the mean creatinine levels of these patients did not vary significantly between baseline and end point measurements (p=0.5405).

Lymphocytes Level
 
At baseline, 27 out of 29 patients had information regarding lymphocytes levels. The mean lymphocytes level of these patients was 1.58 x 109/L with a standard deviation of 0.61 x 109/L and a range of 0.83 to 3.03 x 109/L. Based on the cut-offs for the normal lymphocytes count, which ranges from 0.5 to 4.0 x 109/L, all of the 27 patients had normal blood lymphocytes count. Sixteen (16) out of the 18 survivors had information on lymphocytes level at end point. The mean lymphocytes level of these patients was 1.43 x 109/L with a standard deviation of 0.75 x 109/L and a range of 0.65 to 3.49 x 109/L. Using the paired t-test, it was found that the mean lymphocytes level of these patients did not vary significantly between baseline and end point measurements (p=0.0958).

Association of demographic data and nutritional status indicators with mortality

Table 6 summarizes the crude association of the baseline demographic, anthropometric, nutritional and blood parameters with mortality.

tbl6_bernardo

Mortality Rate

Ten (10) out of the 29 patients expired during the 2-year study period. This translated to an overall mortality rate of 1.68  (95% CI: 0.91, 3.13) per 100 person-months. By demographic characteristics, mortality rate was higher among females (2.08 per 100 person-months) and among patients aged 40 to 59 years (2.82 per 100 person-months). In terms of baseline anthropometric measurements, had normal TSF measurements (2.21 per 100 person-months), had below normal MAC measurements (1.95 per 100 person-months), and had below normal MAMC measurements (1.97 per 100 person-months) were observed to have higher mortality rates. In terms of baseline blood parameters, patients who had relatively “lower” creatinine levels (5.56 per 100 person-months) had higher mortality rates. Table 7 presents the mortality rate of the patients by baseline demographic, anthropometric, nutritional, and biochemical  paramaters.

tbl7_bernardo

Survival analysis was not performed for parameters such as hemodialysis adequacy, modified SGA score, and lymphocytes levels due to the sparseness of the data. The proportion of patients who expired for each level of the said parameters was compared instead, except for the lymphocytes count since all the patients had normal values for this blood parameter.

Among the patients who had adequate hemodialysis, 45.45% (10 out of 29) expired within the two-year study period. Meanwhile, none of the patients who had inadequate hemodialysis (n=4) died within the study period. The result of the Fisher’s exact test showed that the proportion of patients who expired did not vary significantly between the two groups (p=0.250).

Among patients with normal BMI classification, 35% (7 out of 20) expired within the study period. On the other hand, 42.86% (3 out of 7) patients who were underweight died, while none of the overweight patients expired within the two-year study period. However, the result of the Fisher’s exact test showed that the proportion of patients who expired did not vary significantly between the two groups (p=0.837). It is probably because of the limited sample size.

Lastly, none of the patients who had normal baseline nutritional status (based on the modified SGA scoring) expired within the study period. On the other hand, 50% (10 out of 20) of the patients who had below normal baseline nutritional status died within the study period. The result of the Fisher’s exact test revealed that the proportion of patients who expired was significantly lower among the patients with normal baseline nutritional status compared to those with below normal baseline nutritional status (p=0.011). [Figure 3]

fig3_bernardo

End point characteristics of the survivors

Thirteen (13) out of the 18 survivors had information on nutritional status based on the modified SGA score at end point. The mean modified SGA score of these patients was 15.85 points with a standard deviation of 1.99 points and a range of 13 to 20 points. Using the paired t-test, it was found that mean modified SGA score of these patients were significantly higher at end point compared to their mean modified SGA score at baseline (p=0.0010). This implies that the patients’ nutritional status decreased within the 2-year study interval.

Sixteen (16) out of the 18 survivors had information regarding the number of OPD visits. The mean number of OPD visits of these patients was 2.31 visits with a standard deviation of 1.74 visits and a range of 0 to 6 visits. Results of the correlation analyses performed with the baseline anthropometric, nutritional and blood parameters revealed that the modified SGA score was significantly correlated with the number of OPD visits (r=0.5518; p=0.0267) and that the number of visits tend to increase the higher the modified SGA score of the patient. Table 8 presents a summary of the correlation of the baseline anthropometric, nutritional and blood parameters with the number of OPD visits.

tbl8_bernardo

All of the 18 survivors had information regarding the number of hospital visits. The mean number of hospital visits of these patients was 1.67 visits with a standard deviation of 1.57 visits and a range of 0 to 5 visits. Results of the correlation analyses performed with the baseline anthropometric, nutritional and blood parameters revealed that the number hospital visits had the strongest correlation with TSF measurements but its correlation is still not statistically significant (r=0.3598; p=0.1425). Table 9 presents a summary of the correlation of the baseline anthropometric, nutritional and blood parameters with the number of hospital visits.

tbl9_bernardo

DISCUSSION: | Back


This study investigated the impact of some available nutritional indicators on mortality in patients on maintenance hemodialysis. Mortality risk was seen to be significantly associated with some clinical measurements that are connected to nutrition. Mortality risk was noted to be significantly associated with the modified SGA. Given its strong association with mortality, it appears that SGA   provides a meaningful assessment of nutritional status. (9). The SGA is based on subjective and objective aspects of the patients’ medical history and physical examination including any recent weight loss, dietary intake, gastrointestinal symptoms and physical examination of subcutaneous fat and muscle mass.  Although these findings were not confirmed in this study, it was found out in the 2-year follow up that none of the patients who had normal baseline nutritional status (based on the modified SGA scoring) expired. It also revealed that the modified SGA score was significantly correlated with the number of OPD visits and that the number of visits tend to increase the higher the modified SGA score of the patient.

Anthropometric measurements are frequently used to determine protein energy status of chronic hemodialysis patients. BMI presents a simple and easy-to-do assessment tool. Although with some limitations associated with BMI including its inability to differentiate body compartments and gives misleading values in the presence of edema, many studies have shown BMI to be highly correlated with both morbidity and mortality (5). It was observed that in a wide variety of hemodialysis patient, increasing body mass index correlates with decreased mortality (15).   In addition, BMI is strongly associated with survival in hemodialysis patients (16). In this study, among patients with normal BMI classification, 35% expired and 42.86% with low BMI died, while none of the overweight patients expired within the two-year study period. However, the result of the Fisher’s exact test showed that the proportion of patients who expired did not vary significantly probably because of the limited sample size.  Strong correlations were also found among the anthropometric parameters using MAC and MAMC. With below normal MAC and MAMC, higher risk for mortality rate was noted.  In the study of Stosovic, the same anthropometric parameters were found to be independent mortality predictors in which the most predictive anthropometric factor was MAC (9).

Serum creatinine is a valid and clinically useful marker of protein energy nutritional status in dialysis patients. Serum creatinine level is related to nutritional status in that it reflects somatic protein stores, muscle mass and dietary protein intake. According to the study of Usvyat et al of Renal Research Institute of New York, USA, patients lower creatinine levels at baseline (< 5 mg/dL) are associated with poorer survival and increase in creatinine levels in patients with baseline creatinine > 5 mg/dL are associated with improved outcomes (particularly in patients starting with creatinine > 8 mg/dL) (17). It was also seen in the study of Lopes et al. that patients with serum creatinine 7.5-10.5 was associated with lower mortality risk among patients with creatinine >10.5 mg/dL but with higher mortality risk among those with creatinine <7.5 mg/dL (18). As seen in studies, low serum creatinine levels have been ascertained to be highly predictive of future mortality in dialysis patients (19,20), as confirmed also in this study.

Malnutrition might be one of the important factors that can lead to mortality among  chronic hemodialysis patients  Since some nutritional status indicators determine future mortality risk, we have reason to be concerned. Hence, the best decision is to nourish the patient adequately at the time maintenance hemodialysis is prescribed. Therefore, it is fundamental to understand the significant role that nutritional management plays in improving the outcome of  hemodialysis  patients.  Therefore, nutritional assessment should also be routinely performed  in an attempt to reduce nutrition/hemodialysis -related complications. Mortality could be decreased among dialysis patients if there will be an increased attention to their nutritional status. More comparative, longitudinal studies with larger population are needed with the recommendation to include not only anthropometric variables, serum creatinine, and lymphocytes but to also check for serum albumin, total cholesterol and actual calorie and protein intake.


CONCLUSION: | Back

Nutritional status in hemodialysis patients is directly associated with mortality and renal function status.

RECOMMENDATION:

Early assessment of the nutritional status of dialysis patients is recommended to prevent development or progression of malnutrition and to decrease the mortality risk among chronic hemodialysis patients.

 

REFERENCES: | Back

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Abstract | Introduction | Methodology | Results | Discussion | References | Back to Articles Page