Frailty
Frailty encompasses the deterioration of a wide variety of systems. The Japanese Society of Gerontology issued a statement regarding frailty in 2014. The statement describes this condition as the reduction of physiological reserve due to advanced age, increase in vulnerability to insults, and a predisposition to conditions relating to worse outcomes, such as disability or even death. The scope of frailty is wide, and many concepts of frailty have been proposed, including physical frailty, cognitive frailty, oral frailty, and social frailty. The major point in this concept is that frailty is a reversible condition: appropriate management can reverse it, and early intervention is warranted [2].
Fried et al. [8] described the criteria for physical frailty in the Cardiovascular Health Study. Several other definitions have been proposed, but most are based on the cardiovascular health study criteria. Two meta-analyses reported the incidence of frailty among patients with ESRD. One revealed that the incidence was 37% for objective criteria (95% CI 30–44%) and 67% for patient-reported criteria (95% CI 59–75%) [9]. The other showed similar results, with an incidence ranging from 14 to 73% in hemodialysis patients [10].
A well-known study by Johansen et al. [11] demonstrated that frail patients had higher all-cause mortality (HR 2.24; 95% CI 1.60–3.15) and a higher rate of the composite endpoint of combined death and hospitalization (HR 1.56; 95% CI 1.36–1.79). A meta-analysis of elderly community dwellers showed that frailty was significantly associated with a higher incidence of falls (OR 1.84; 95% CI 1.43–2.38), potentially leading to worse survival [12]. A study investigating factors that promote frailty in dialysis patients found that higher interleukin-6 and hospitalization in the last year were significantly associated with the progression of frailty scores [13].
Other types of frailty have a substantial impact on clinical outcomes. Social frailty can be associated with the progression of disability and loss of activities of daily living (ADL). Oral frailty is also associated with physical frailty, sarcopenia, progression of disability, and death, although these findings were from a study involving older persons living in the community [14]. In relation to oral frailty, dialysis patients have substantial problems with oral health. A meta-analysis demonstrated that gingivitis can be found in 56.8% of them (95% CI 39.3–72.8%) and that 20.6% (95% CI 16.4–25.6%) were edentulous [15]. The latter condition can mitigate an appropriate dietary intake.
Management of Malnutrition-Wasting Conditions
Many interventions have been used to address malnutrition-wasting conditions with the aim of improving survival in dialysis patients. Recently, two strategies, nutritional management and exercise training, have been considered crucial and thus are becoming more widely used. Let us now look at the efficacy of these two modalities.
Nutritional Management
Achieving adequate protein and energy intake are the two key components of nutritional management in dialysis patients. In terms of protein intake, many studies have demonstrated that a higher normalized protein catabolic rate (nPCR), which is an index of protein intake in steady state patients, is associated with better survival. A study investigating nPCR at the time of initiation of dialysis revealed that changes in nPCR during the first 6 months were positively associated with higher serum albumin subsequently and improved 5-year survival [16]. Moreover, we previously demonstrated that changes in nPCR for 4 months were positively and significantly associated with changes in creatinine generation rate, which is an index of muscle mass in the body [17]. These findings reinforce the hypothesis that protein intake might enhance the nutritional status and prevent wasting conditions in dialysis patients.
In terms of the second key component of nutritional management, energy intake, a 1989 study investigated the effect of energy intake on nitrogen balance and body weight changes in hemodialysis patients who consumed a sufficient amount of dietary protein, namely, 1.1–1.2 g/kg/day. They found that a higher energy intake, or 45 kcal/kg/day, was associated with a positive nitrogen balance and an increase in body weight within 3 weeks. In contrast, a lower energy intake, or 25 kcal/kg/day, was associated with a negative nitrogen balance and a reduction in body weight [18].
In the context of these findings, an important challenge is that older dialysis patients often experience a reduced appetite, which can jeopardize sufficient nutrient intake. A study investigating voluntary dietary intake of protein and energy found that an intra-dialytic parenteral nutrition (IDPN) regimen containing 16 kcal/kg/session of lipid and amino acids corresponding to 0.08 g/kg/session of nitrogen enhanced the voluntary protein and energy intake from daily food [19]. Another study demonstrated that essential amino acids containing branched amino acids improved dietary protein and energy intake in hemodialysis patients [20]. These results indicate that proper nutritional management can enhance dietary intake and improve nutritional status, getting patients started on a favorable cycle.
Nutritional intervention during dialysis sessions has become popular. Patients who receive oral nutritional support (ONS) during dialysis sessions have an almost 30% lower risk of death, especially those with lower serum albumin levels [21]. A recent study in which patients were given either a protein- and energy-rich diet or a low-protein diet during dialysis sessions showed that those on the protein-rich diet exhibited an increase in serum albumin for only 8 weeks [22]. International Society of Renal Nutrition and Metabolism guidelines on food intake during hemodialysis sessions describe the advantages and disadvantages of food intake during sessions and recommend dietary intake if it can be tolerated by the patient [23].
On the other hand, there are still concerns about food intake during hemodialysis, such as hypotension, vomiting, aspiration, and asphyxiation. Patients with malnutrition-wasting conditions often experience these complications. Moreover, the loss of appetite often seen in older dialysis patients can prevent them from eating during dialysis therapy. IDPN can be of help in such patients. Even though IDPN did not exhibit the add-on effect seen with ONS in randomized controlled trials performed in patients with malnutrition-wasting conditions [24] and some of the nutrients provided through IDPN can be eliminated during the dialysis process, the intervention can improve nutritional status in those patients who are not eligible for dietary intervention or cannot eat enough food [19]. As such, the European Society of Parenteral and Enteral Nutrition guidelines for kidney disease patients recommend IDPN for patients who have insufficient dietary intake and who are not adherent to ONS [25]. Therefore, IPDN itself is an option for nutritional therapy.