Introduction

End stage renal disease (ESRD) is a recognised public health problem worldwide [1]. The increasing prevalence of ESRD parallels the increasing prevalence of type 2 diabetes mellitus. The total number of people with diabetes is projected to rise from 336 million in 2012 to 522 million in 2030 [2]. In South Asia, particularly India and Pakistan, diabetic nephropathy is the second highest cause of ESRD [3,4]. There is increasing evidence that diabetes mellitus (DM) patients have higher incidence rate of dialysis compared to their non-DM counterparts [5,6]. It is thus projected that the incidence of ESRD will increase in the future due to the “diabetic epidemic” [7].

The most preferred treatment modality for ESRD in Malaysia is hemodialysis (HD). The prevalence of ESRD patients on dialysis has tripled from 7837 in 2001 to almost 23,000 in 2010 [8]. Hemodialysis improves serum creatinine, albumin and prealbumin, normalises the protein catabolic rate (nPCR) as well as increases the dietary intake of patients [9,10]. Despite its advantages, HD is highly associated with malnutrition and lower quality of life (QOL) [11,12]. Severe malnutrition among HD patients is reported to be approximately 4.6% - 19%, while 72% - 90.9% are mildly malnourished [11-14].

Quality of life (QOL) in patients with ESRD is influenced by the types of renal replacement therapy. Patients who underwent kidney transplant (KT) achieved better QOL compared to dialysis patients [15]. Wu et al in a follow-up (prospective) study found that HD patients showed greater improvement in SF-36 domain scores than peritoneal dialysis patients [16]. Among HD patients, the mental health and physical health dimensions of QOL are strongly associated with morbidity and mortality [17,18]. Nutritional status is an important factor that determines the QOL of patients undergoing dialysis treatment. Body mass index (BMI), cholesterol, serum albumin, hemoglobin and dietary intakes may influence QOL [19,20]. Other factors associated with QOL of HD patients are HD duration, age, ethnicity [21-23].

In Malaysia, information on QOL among HD patients is limited. Most studies conducted were on QOL and its associated factors in different health conditions such as asthmatic, coronary artery bypass and thalassaemia patients [24-26]. A limited number of studies have examined the relationship between socio-demographics, treatment characteristics and nutritional status with QOL among hemodialysis patients [12,27]. However, these studies did not assess comprehensive factors associated with QOL. Thus, the present study aimed to determine the relationship between medical history, hemodialysis treatment and nutritional status with quality of life in hemodialysis patients. We hypothesized that the QOL of HD patients could be influenced by the presence of co-morbidities and current treatment and nutritional status.

Methods

Results

The respondents comprised 44 (48.9%) males and 46 (51.1%) females with a mean age of 49.7 ± 14.1 years (Table 2). Chinese (n = 62, 68.9%) were the largest group recruited, followed by Malays (n = 19, 21.1%) and others (n = 9, 10.0%). As the majority of the respondents were unemployed (n = 64, 71.1%), only a small group had a household monthly income of more than RM 3000 (n = 21, 23.3%). The most frequent aetiologies of ESRD were unknown causes (n = 30, 33.3%), followed by DM (n = 20, 22.2%), glomerulonephritis (n = 7, 7.8%), hypertensive nephrosclerosis (n = 7, 7.8%) and systemic lupus erythaematosus (n = 6, 6.7%). There was no further documentation on the type of diseases or conditions that contributed to the unknown causes in the respondents’ medical records. The exact diagnosis is not known. All respondents were dialysed three times/week for four hours per session, even those with a monthly income of RM 2000 or less. Since 2001, the Malaysian government has been subsidising RM 50 for each HD treatment for low-income patients receiving HD treatment at government and non-government dialysis centres [36]. The average duration of dialysis of the respondents was 55 ± 39 months, ranging from 4 – 56 months. The mean Kt/V was 1.6 ± 0.5, and average blood flow was 297.1 ± 38.5 ml/minute.

The mean dry weight and body mass index (BMI) of respondents were 57.7 ± 13.0 kg and 22.8 ± 4.7 kgm^-2, respectively (Table 3). Approximately 26 (30%) of the respondents achieved the recommended BMI for HD patients, which is BMI ≥ 24 kg/m² [32]. The mean for triceps skinfold (TSF) was 13.3 ± 6.2 mm, and mid-arm circumference (MAC) was 27.1 ± 4.4 mm. Approximately 72 (80%) and 31 (34%) of the respondents had TSF and MAC less than the 50^th percentile [32]. Only one respondent was severely malnourished. The respondent was a female who complained of being physically weak and was experiencing loss of appetite. More than half (n = 49, 54.4%) of the respondents were mildly-moderately malnourished while the others (n = 40, 44.4%) were well-nourished.

The mean serum calcium and serum phosphate were 2.3 ± 0.2 mmol/L and 1.8 ± 0.6 mmol/L, respectively. The majority of respondents (n = 87, 96.7%) had a normal serum calcium level. More than half of the respondents (n = 51, 58.6%) had elevated serum phosphate. Approximately 13 (14.4%) of respondents had a serum albumin level lower than 35.0 mg/dL. The mean total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides (TG) were 4.9 ± 1.1 mmol/L, 1.1 ± 0.3 mmol/L, 2.8 ± 0.7 mmol/L and 2.1 ± 1.3 mmol/L, respectively. There were 26 (28.8%) respondents with elevated total cholesterol and 43 (47.8%) respondents with elevated TG. Most respondents (n = 65, 72.2%) had HDL below the recommended range (> 1.2 mmol/L), but LDL (n = 82, 91.1%) in the recommended range.

Based on the MNT, the recommendation for energy intake for respondents more than 60 years old is 30-35 kcal/kg body weight and for those who are less than 60 years old is 35 kcal/kg body weight [32]. In the study, the mean total energy intake was 26.8 ± 7.0 kcal/kg body weight, with a higher mean intake in respondents aged less than 60 years old (26.9 ± 6.1 kcal/kg body weight) than for 60 years and above (24.3 ± 7.0 kcal/kg body weight). Approximately 72 (80%) of respondents had inadequate energy intake. For protein, the mean intake was 1.1 ± 0.4 g/kg, with 68 (75.6%) of the respondents failing to achieve the recommended protein intake (1.2 g/kg) [32].

The overall scores of the SF-36 are presented in Table 4. The mean total score for SF-36 was 54.1 ±19.2, while the mean for PCS and MCS were 39.6 ± 8.6 and 45.0 ± 8.6, respectively. For PCS, pain had the highest score (66.9 ± 24.3), while role limitations-physical had the lowest score (30.3 ± 38.5). For the MCS, the highest score was social function (66.8 ± 26.0) and the lowest score was role limitations - emotional (49.3 ± 45.9). It shows that the kidney disease had a greater effect on physical health than on mental health.

Table 5 shows the relationship between medical history, HD treatment and nutritional status factors with the QOL of HD patients. Factors associated with a higher MCS score were absence of diabetes mellitus (p=0.004) and lower serum calcium (p=0.016), while higher blood flow (p=0.000), higher serum creatinine (p=0.000) and lower protein intake (p=0.006) were associated with a higher PCS score.

Discussion

There was comparable disposition among males and females in this study. In the study, DM (n = 20, 22.2%) and unknown causes (n= 30, 33.3%) were the two main primary renal diagnoses among the respondents. A study conducted at the east coast of Malaysia found that 48% of diabetic patients had proteinuria and 16% microalbumia, which are the earliest indicators of diabetic kidney disease [37]. In this study, the mean Kt/V was 1.6 ± 0.5, which was higher than the recommended value, and the majority of the respondents (88.8%) were adequately dialysed. Tarek et al found that achieving a Kt/V of 1.5 was a more suitable target for HD patients because it might be an avenue for improving the neuromuscular functions of patients [38].

In the study, the increase in the percentage of HD patients with higher BMI (more than 25 kg/m²) was due to the increased number of HD patients with diabetes as a consequence of diabetic nephropathy [27]. On the other hand, Ohkawa et al reported that the composition of muscle mass, fat mass and fat distribution differed among HD patients with an increased number of years on HD treatment [39]. Ishimura et al stated that although HD patients may have satisfactory BMI, their ratio of muscle mass and fat mass changed as an outcome of HD treatment [40]. Higher BMI, hypercholesterolaemia, hypercreatininaemia and hyperhomocysteinaemia were reported as protective factors against cardiovascular disease among HD patients in contrast to the general healthy population [41]. According to the Subjective Global Assessment (SGA), the majority of the subjects were mildly malnourished (54.4%) or well nourished (44.4%). Only one subject was severely malnourished. The results of this study were comparable to those of Jones et al. [14]. A total of 69% of their patients were well nourished, 30.5% mildly nourished and none was severely malnourished. In contrast, Rutledge and McMahon documented a high percentage of malnourished patients in their study (19% severe, 25% moderate and 28% mild malnutrition) [11].

Elevated serum phosphate level indicates hyperphosphataemia. Elevation of serum phosphate was mainly caused by dietary non-compliance [42]. Consistent hyperphosphataemia was associated with the development of myocardial hypertrophy and poor bone health [43]. Only a small percentage of the respondents had elevated serum calcium. Overall, the mean serum calcium and serum phosphate were comparable to the 13^th Report of the Malaysian Dialysis and Transplant Registry at 2.3 mmol/L and 1.8 mmol/L, respectively [27].

In this study, the majority of respondents had low HDL levels, and about half of the respondents had elevated TG levels. The results were consistent with the study by Piperi et al. [44]. Increased cholesterol level among HD patients has been strongly associated with the development of CVD, which is one of the causes of death among HD patients [45]. The low mean HDL values may also be due to lack of physical activity, as most of the HD patients were inactive due to the effects of the HD treatment [46].

The majority of the respondents failed to achieve the recommendation for both energy and protein intake. This result was consistent with Bossola et al [47]. They reported that the percentage of patients who did not achieve the recommended intake of energy was higher than the percentage of the patients who did not achieve the intake of protein. They also found a small portion of the patients did not achieve the recommended intake for both energy and protein. Decreased energy intake was negatively associated with the presence of anorexia and increase of age in HD patients [47].

Daily mean intake of phosphate was high, while none of the respondents had excessive intake of potassium. Durose et al found that patients had difficulties in reducing the intake of food high in phosphate [42]. However, they had complied with reduced intake of food high in potassium. As a consequence, serum phosphate was elevated but serum potassium remained in the normal range. The intake of fluid was higher in 68.9% of the respondents. This was comparable with the results of Kugler et al., who reported that the degree of non-adherence of fluid intake was high (74.6%) among their respondents [48].

Patients on HD treatment are at risk of having poor quality of life [12]. Previous studies have shown that the mental and physical health dimensions of quality of life displayed a strong association with morbidity and mortality [15-18]. In the present study, physical and mental quality of life among HD patients is influenced by several health and nutritional factors.

Tanaka et al showed that HD patients with high serum calcium (>2.6 mmol/L) were more likely to have poor mental health. They found that a significantly lower mental health score was identified in patients with corrected calcium > or = 11 mg/dl than in <8.4 (P = 0.04), > or =8.4 to <10.2 (P = 0.009) and > or =10.2 to <11 mg/dl (P = 0.003). The association was significant even after adjustment for age, sex and other confounders [49]. However, the mechanism involved in the association between serum calcium and the mental dimension of quality of life has not been adequately addressed in clinical studies. Several studies have reported that elevated serum calcium was associated with increased mortality in dialysis patients because it increased the risk of cardiovascular diseases [50,51]. Kalantar-Zadeh et al showed that mortality was strongly associated with a low mental dimension of QOL among HD patients [17]. Therefore, for patients on HD, serum calcium in the low-normal range is important to minimise the complications associated with high serum calcium and to improve quality of life [49-51].

The present study found that serum calcium was negatively associated with MCS of QOL. There are limited studies on the effects of low serum calcium on mental health status or mortality [17,50,52]. According to Miller et al, high (> 2.5 mmol/L) calcium levels was consistently associated with mortality. Whereas, association between low (<2.25 mmol/L) calcium and mortality was more prominent among patients with higher serum phosphorus (1.1 mmol/L) and PTH (> 150 pg/ml) [52]. In our study, 64.4% of respondents had serum calcium in the range of 2.25 - 2.5 mmol/L. As the majority of respondents had serum calcium within the normal range, this could explain the better MCS of QOL with lower serum calcium observed in this study.

The present study showed that the absence of DM is associated with better mental quality of life. Previous studies reported that non-diabetic patients had better MCS compared to DM patients [53,54]. It was found that a combination of DM and chronic medical condition (renal failure) might adversely affect the mental dimension as measured by SF-36 [54]. This association could be explained by the better overall health status of HD patients without DM compared to those with DM. Diabetic patients on HD have a higher burden of morbidity and mortality due to risk of microvascular and macrovascular such as cardiovascular diseases, cerebrovascular events and peripheral vascular disease than non-diabetic patients on dialysis [55]. Several studies found that a combination of DM and chronic medical conditions such as renal failure might adversely affect mental health status such as vitality, social functioning and role-emotional as measured by SF-36 [56,57].

We found that higher blood flow and serum creatinine as well as lower protein intake were associated with better physical quality of life. In the present study, 63.3% of the respondents had blood flow of 300 ml/minute and above. High blood flow is correlated with Kt/V, which is a measure of dialysis adequacy [57]. The variations in blood flow and dialysate flow were positively related to the variation of the indexes Kt/V and protein catabolic rate (PCR) and consequently to the HD adequacy [56]. Defining a Kt/V of 1.2 as a minimum level of dialysis adequacy (K/DOQI, 2000), 88.9% of the respondents were adequately dialysed. Borzou et al showed that increasing the blood flow rate by 25% is effective in increasing Kt/V [57]. Patients with average Kt/V levels of greater than or equal to 1.3 had better HRQOL as measured by significantly higher scores (p<0.05) in 6 of 8 SF-36 domains (physical functioning, general health perceptions, emotional well-being, role-emotional, social function, and energy/fatigue) [58].

Similar to the results of Kalantar-Zadeh et al, the present study showed that a high serum creatinine level is associated with better PCS of QOL [59]. The serum creatinine level is proportionate to dietary protein intake and somatic (skeletal muscle) mass. As only a small percentage of HD patients in this study (10 %) were not adequately dialysed (10%) and had adequate protein intake (24%), serum creatinine should be more indicative of somatic protein concentration (muscle mass) rather than high protein intake [60]. Allen et al also found that an increase in serum creatinine was associated with the increase in the PCS of quality of life and Karnofsky Index (KI) scores. In their study, physical functioning tasks listed in the PCS and assessed by KI were focused on the physical functioning of the lower extremity that is related to mobility [60]. It was concluded that the association between high serum creatinine and better PCS was due to the better status of muscle composition, especially in the lower limbs. In a study among pre-transplant patients, Streja et al documented that larger pre-transplant muscle mass, reflected by higher pre-transplant serum creatinine level, was associated with better graft and patient survival [61].

Protein is an important nutrient to be considered in the management of HD patients. HD patients are required to follow the recommended protein intake of 1.2 g/kg body weight to attain better nutritional status [28-32]. Ohri-Vachaspati and Sehgal showed that inadequate protein status or protein intake, reflected by low serum albumin level and low protein catabolic rate, was independently associated with poor QOL [62]. In another study, Morsch et al found that low serum albumin was associated with low physical functioning [63]. Kalantar-Zadeh et al also showed that patients with a higher serum albumin level had better quality of life in terms of physical and mental health [17].

In the present study, we found that low protein intake was associated with better PCS. Further analysis of patients with adequate and inadequate protein intake revealed that the inadequate protein group had better mean serum albumin, better BMI status (not significantly different) and high PCS score (t=-2.857, p=0.004) compared to the adequate protein intake group. Although the inadequate protein group did not achieve protein intake recommendation, they still managed to have good nutritional status, which could contribute to better PCS.

Another explanation for the low protein intake and better PCS observation in this study is related to the accuracy of reporting of protein intake by the HD patients given that the use of diet recall and records is not without limitations [60]. It has been suggested that Normalised Protein Catabolic Rate (nPCR) is a better method for protein intake assessment as it is a valid and clinically useful measure of protein degradation and protein intake in dialysis patients [26]. Kloppenburg et al suggested that an estimation of dietary protein intake and dietary energy intake required at least three PCR measurements or seven and five food recording days, respectively [64].

Several points should be considered in interpreting the results. First, is the accuracy of the 24-hours dietary intake and food record, which is highly dependent on respondent’s memory and cooperation from the family members to complete the food record. A recommended method to assess the validity of dietary intake, especially dietary protein intake is the Protein Equivalent of Total Nitrogen Appearance (PNA) or Protein Catabolic Rate (PCR). Protein Catabolic Rate (PCR) is a valid and clinically useful measure of net protein degradation and protein intake in the maintenance of dialysis patients [28]. Kloppenburg et al suggested that an estimation of DPI and DEI required at least three PCR measurements or seven and five food recording days respectively [64]. Therefore, in future, it is important to include measurement of PCR.

Second, to assess the effect of under-reporting of dietary intake in this study, basal metabolic rate of respondents was calculated using the predictive equation by the World Health Organization (WHO) (FAO/WHO/UNU, 1985) [65]. The ratio of energy intake (EI) to BMR was calculated. The ratio of EI to BMR of less than 1.2 is not compatible with habitual intake and normally signifies under-reporting of energy intake [66]. From the study, the mean for the ration EI to BMR was 1.13 ± 0.24. Only 38% of the respondents had EI:BMR exceeding 1.2. Hence, the majority of the respondents were under-reporting their dietary intake.

In future, a longitudinal study is required in order to observe the determinants of poor QOL and associated factors. In addition, a comphrehensive assessment consists of Protein Equivalent of Total Nitrogen Appearance (PNA) or Protein Catabolic Rate (PCR), repeated biochemical analysis and details analysis on body composition such as Dual Energy X-ray Absorptiometry (DEXA) should be included. There is growing evidence of a potential link between hypercalcemia and mental health among HD patients. It is recommended that future studies should delineate the pathophysiology or mechanism relating hypercalcemia to mental health as well as long-term implications of hypercalcemia on HD patients. Despite these limitations, our findings that poor quality of life among HD patients is associated with co-morbidities, poor nutritional status and inadequate treatment, are consistent with those reported in other settings [17,18]. These findings confirm the universal importance of addressing these factors in efforts to improve health and quality of life of HD patients.

In conclusion, the present study provides an understanding of factors that are associated with QOL in HD patients. It is important for health professionals to emphasise that low blood flow, DM, increased serum calcium and low level of serum creatinine factors can potentially impair the overall QOL of the HD patients. Low QOL among HD patients is closely associated with higher risk of morbidity and mortality . With the rising prevalence of DM and ESRD worldwide, there could be increasing demand for diabetes-related ESRD treatment, particularly hemodialysis [3-8]. The development and implementation of multidisciplinary interventions consisting of psychosocial and specific medical and dietetic strategies that focus on factors associated with mental and physical quality of life are warranted to prevent further health complications and to improve quality of life of hemodialysis patients.

Acknowledgments

The authors acknowledge the HD patients for their support, help and co-operation in this research.