We found a very high prevalence (41.2%) of low muscle mass, similar to other studies of HD patients [2, 18]. Isoyama et al. found low muscle mass prevalence of 44% in an ongoing cohort of HD patients from Baxter Clinics [2]. Valtuille et al., studying a sample from nine HD centers in Argentina comprising 934 patients, found 58.8% prevalence of low muscle mass, as defined by low LTI [17]. It is important to highlight that our sample as well as the samples of the cited studies were formed not just of elderly patients, but with mean ages of 51.3 (our study), 53 [2] and 58 years [18]. This high prevalence of low muscle mass in a sample of relatively young patients is clinically important. Low muscle mass is a predictor of mortality with an odds ratio for death varying between 2.3 and 3.2 [10, 19]. Moreover, low muscle mass impacts quality of life, impairing the execution of daily activities (dressing, rising, eating, walking, hygiene, reaching, gripping), as we found in our sample, which was evaluated by the HAQ-DI questionnaire. The difference of the scores generated by the HAQ-DI is substantial. The maximum score is three, and the higher the score, the greater the degree of disability is. We found median of 0.2 among patients with normal muscle mass versus 0.6 in patients with low muscle mass (p < 0.001).
Among the variables associated with low muscle mass in our study, age was expected to be found since low muscle mass is a consequence of aging. Unlike our study, another study found that overhydration and longer time on HD were predictors of LTI [18]. We think that the lack of association between serum albumin and muscle mass has great clinical significance. Albumin is a traditional nutritional marker, widely used in the follow-up of HD patients. However, as has already been shown, serum albumin reflects muscle wasting only when its level is very low. In our sample, the mean serum albumin was 4.2 md/dL (normal value), even among patients with a high prevalence of low muscle mass. Thus, albumin is only a marker of very advanced stages of muscle wasting. On the other hand, another traditional nutritional marker used in ESRD was strongly associated with muscle mass: creatinine. Creatinine levels are measured monthly in dialysis centers, and in stage 5 chronic kidney disease it is useful not as a marker of renal function (as it is in earlier stages of chronic kidney disease), but as a nutritional marker, specifically associated with muscle mass. The monthly checking of serum creatinine is still the most simple and reliable way to assess muscle mass among HD patients.
Abnormal waist-to-hip ratio is a predictor of cardiovascular events in the general population. Recently, this anthropometric metric was also validated as a predictor of death and cardiovascular events among ESRD patients. Abnormal waist-to-hip ratio was found to be an independent predictor of mortality and ischemic heart disease in peritoneal dialysis patients [20]. In our study, abnormal waist-to-hip ratio was an independent predictor of low muscle mass. It is a simple and inexpensive marker that can be measured routinely as a screening tool to identify patients at risk of low muscle mass.
Our finding that FIT predicts muscle mass (in a negative correlation, the higher the FTI, the lower the LTI) calls to mind a current question related to patients undergoing HD: the so called sarcopenic obesity. Also, other results reinforce this issue in our sample: among patients with low muscle mass compared to patients with normal muscle mass, there were more obese people according to the sum of four skinfolds (45.3% vs. 26.3%; p = 0.049) and more patients with high risk waist circumference (31.5% vs. 16.6%; p = 0.019). Indeed, protein-energy wasting has been the central issue for many years in studies about nutritional status in HD patients. The pattern of protein-energy wasting as the main nutritional complication among ESRD patients is changing. In a recent study, obesity was found in 43% of HD patients and at least a portion of them presented low LTI [21]. On the other hand, protein-energy wasting was uncommon, affecting only 4% [21]. The condition of “sarcopenic obesity” among HD patients is emergent and was well detected in our study. Novel approaches for this emergent condition among ESRD patients on HD should be considered in the future.
In medical care, especially of groups of patients with chronic diseases associated with high mortality, warning markers contribute to identify patients at risk, giving an opportunity to implement targeted and individualized interventions. This fact was the main motivation for this study. Thus, interventions aiming to increase muscle mass should be tried in patients at risk, based on three aspects: diet/intake, physical activity and hormone therapy. At first glance, the increase in protein intake seems to be the simplest to measure. However, an increase in protein intake could exacerbate metabolic acidosis, and metabolic acidosis is one of the factors provoking muscle wasting. Thus, it is necessary to use supplements (amino acids) with high biological value to minimize the generation of acidosis [22]. These supplements are expensive, making their use by patients with very low economic class like ours virtually impossible. Regarding physical activity, there is evidence that resistance exercise is efficient to increase muscle mass [23]. But once again, characteristics of ESRD makes this simple remedy difficult: anemia, hypertension and renal osteodystrophy are impediments to regular exercise among HD patients. Electric stimulation and acupuncture are promising approaches that can be tried on bedridden patients, based on a study of mice [24]. Another promising approach is the use of nandrolone decanoate (an androgenic steroid). In phase II clinical trials, this hormone was found to increase muscle mass without provoking fluid overload [25]. However, in female patients androgenic steroids could be intolerable due to the risk of virilization.
In our opinion, these interventions against muscle wasting can fail because patients undergoing HD are typically in a very advanced phase of muscle wasting. This is an important point when considering interventions. One study comprising patients not only on HD (stage 5 of chronic kidney disease), but in earlier stages (stages 3 and 4), showed a lower prevalence of low muscle mass compared to the prevalence in HD patients: 12.2% vs. 41.2% [26]. Thus, we think that interventions based on variables associated with low muscle mass, like the variables we found, should be implemented, preferably in earlier stages of chronic kidney disease. Interventions will likely be less efficient in advanced stages, when patients are already undergoing HD. Last, we should mention that our low muscle mass criterion was based on strength, and decreased strength certainly indicates advanced muscle wasting. Whether or not interventions will revert or improve muscle wasting in such advanced phases remains speculative. Prospective studies would be welcome to check if interventions to increase muscle mass can produce positive results, and mainly to verify if increased muscle mass can positively affect mortality and quality of life.
Our study has several limitations. Since the study is preliminary, trying to find a LTI cutoff to define low muscle mass, our proposed cutoff cannot be assumed to apply to other Brazilian samples. In our region, there are also fewer diabetics. Samples with more diabetics can have a different cutoff due to known effects of diabetes on muscles. Second, we assumed that LTI is equal to muscle mass because the BCM ® device is specifically designed to distinguish muscle mass from pathologic fluid retention. However, LTI is the sum of muscle mass and fluid. To increase confidence in the BCM ® device’s results, we performed bioimpedance analysis after dialysis sessions when excess of fluid is supposed to have been removed. Nonetheless, the finding of 60% overhydration in patients with low muscle mass cannot prelude the bias of underestimating muscle mass. Even so, in multivariate analysis overhydration was not associated with muscle mass. Third, as shown by other studies, inflammatory markers could be associated with muscle mass and these were not considered in our work. However, our main intention was to study traditional and routinely used markers. Interleukin 6 and tumor necrosis factor alpha measurements are expensive and not routinely performed in dialysis centers.