Our study demonstrated the utility of HGS in predicting mortality in MHD patients. Utilizing this simple tool to identify MHD patients at an increased risk of death may be beneficial for healthcare systems. The results of the present study can be used to identify MHD patients who are at a high risk for mortality. Together with the subjective global assessment or malnutrition inflammation score, HGS offers other important tool for nutritional assessment.
HGS is a widely used measure in clinical practice because it is a simple, easy-to-determine, non-invasive, and reliable nutritional marker . In fact, HGS has been recognized as a simple and easy-to-measure variable that correlates with lean mass in patients soon after the start of dialysis . Additionally, several studies have shown that HGS is a good indicator of nutritional status, enabling the early diagnosis of malnutrition due to changes in muscle function [5, 8-10].
Moreover, our results indicated that HGS can identify an increased risk of mortality in both male and female MHD patients, with a different cut-off for each sex. This study provides direct evidence supporting HGS as a valid tool for predicting mortality in Taiwanese MHD patients. The optimized cut-off point for HGS as a predictor for mortality in males was 26 kg and 17 kg in females. According to the 2019 Asian Working Group for Sarcopenia (AWGS) recommendation [11, 12], the diagnostic cut-off point for low muscle strength is HGS < 28.0 kg for men and <18.0 kg for women among elderly Asian populations (age > 65 years). In comparison, the HGS cut-off points for poor outcomes in dialysis patients are relatively lower than those in the elderly population.
The mechanisms and mediators underlying the association between low HGS and high mortality risk are not fully understood. Several mechanisms have been hypothesized to explain the significant association of muscle strength and mortality. Physical disability and cognitive decline are risk factors for higher mortality in old-aged populations, which may be a result of reduction in muscle mass [13-17]. For example, low muscle mass may increase the risk of falls in elderly people, resulting in a greater risk for disability and, consequently, death. However, previous reports have shown that resistance training enhances muscle quality, reduces the risk of cardiovascular disease, and improves the quality of life in the general population . In our study, the non-surviving group had a higher proportion of patients with cardiovascular disease. Moreover, muscle strength is considered a marker of nutritional status [19, 20]. Malnutrition has been recognized as a definite predictor of mortality in HD patients . Nutritional status is usually reduced in chronic diseases, and malnutrition also exerts a substantial impact on muscle strength. A poor nutritional status is more associated with increased risk factors for death, such as infection. The above reasons may explain the association between HGS and mortality risk (Fig. 3).
Most previous studies that examined the association between muscle strength and death were performed in Caucasian patients or in patients of African descent. Recent studies investigated the association between muscle strength and death in the Japanese population [1, 22]. These studies confirmed that low muscle strength is associated with an increased risk of mortality in Asian populations. Similarly, we applied HGS to the Taiwanese dialysis population, and our results also proved the correlation between muscle strength and mortality.
Although diagnostic cut-off points for low muscle strength of HGS < 28.0 kg for men and HGS < 18.0 kg for women were recommended by the AWGS 2019 for elderly Asian populations [11, 12], there is a lack of consensus on HGS reference values for dialysis patients. Leal et al.  showed in their systematic review that the HGS values of dialysis patients range from 12 to 38 kg in men and from 12 to 26 kg in women. In the study by Vogt et al.  (N = 265; HD: 82.3%, peritoneal dialysis: 17.7%), the HGS cut-off values were 24 kg for men and 12.5 kg for women. In the study by Matos et al.  (N = 443), HGS values of 28.3 kg for men and 21.5 kg for women were the best cut-off points for predicting mortality in Brazilian HD patients. Moreover, the values were 26 kg for males and 17 kg for females in our study. As in the general population, a large discrepancy in muscle strength is observed in MHD patients according to age, race, and sex. In summary, the difference of muscle strength between the sexes is already well known. Moreover, recent studies have proved that different races and ages are associated with different cut-off values [3, 12, 22, 24, 25].
Muscle mass assessed using MAMC area and TSFT had no significant difference between survivors and non-survivors in our analysis. In contrast, higher HGS and higher Kt/V were both significant independent predictors for better outcome in HD patients, similar to the results of previous studies. In the study by Isoyama et al.  (N = 330), decreased muscle strength was more strongly associated with mortality than decreased muscle mass in dialysis patients. Lopes et al.  included 413 patients with <3 months of HD in their study. However, other studies that investigated the association between HGS and mortality in the MHD population mainly comprised prevalent patients with >6 months of dialysis. The results presented here might have been influenced by the HD vintage, which was 72–75 months in our study. Another previous study suggested that muscle mass wasting is highly prevalent among MHD patients, with significant evidence of wasting in 18–75% of the patients . The longer the HD vintage, the greater the possibility for muscle strength reduction. Therefore, the cut-off point might be different in patients with different dialysis vintages. However, uremic toxins may play an importance role in muscle wasting, which might explain why the cut-off for low muscle strength in HD patients is lower than that in the general population. Furthermore, a lower mortality rate was observed in patients with higher uremic toxin clearance in our study.
Strength training is associated with important clinical outcomes, including increased muscle strength and improved self-rated physical health and function. However, particularly in HD patients, it may be difficult to increase muscle mass with strength training. Muscle growth may be impaired as a result of several catabolic conditions, such as insulin resistance, reduced levels of and resistance to anabolic hormones, acidosis, or chronic inflammation . In our analysis, patients with high Kt/V had a lower mortality rate. Therefore, a high quality of HD can reduce the accumulation of uremic toxins and consequently reduce muscle wasting. In other words, simple muscle training might play a limited role in improving muscle strength in HD patients. Clinicians should pay more attention to the dialysis quality or the nutritional status of patients rather than to muscle training.
This study had several methodological limitations. First, our sample was limited to the Taiwanese population, which mainly consisted of Asian patients. Therefore, this may limit the extrapolation of our findings to other ethnic groups. Second, definite causal conclusions cannot be reached in our analysis owing to its prospective observational nature. For example, it is not possible to evaluate whether the association of HGS with mortality varies according to the cause of death. Nevertheless, previous studies have indicated that the mortality risk associated with nutritional indicators is usually due to cardiovascular disease .
Although the results of this study showed the association of HGS with mortality in both male and female MHD patients, randomized controlled trials are still required to confirm our results. Third, our sample size was small, and patients were enrolled from a single medical center. Finally, we addressed the mortality risk based on single-point measurements of muscle strength in the beginning of the study. Because HGS was measured only at the start of the study, our data were not suitable for determining the influence of changes in muscle strength during the follow-up on mortality risk. A time-averaged analysis based on sequential measurements during the follow-up period may provide more direct evidence on the association between muscle strength and prognosis in MHD patients.
Further studies are required to assess whether serial changes in muscle function may better predict mortality than a single measurement in MHD patients. Age-specific HGS should also be assessed in future investigations. In addition, further studies should be conducted to evaluate the association between HGS and mortality risk in PD patients. HGS may also play a role in predicting mortality in the PD population.