CKD-Associated Complications: Progress in the Last Half Century. Группа авторов

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СКАЧАТЬ conditions, the strategies to address them, and the heterogeneity of the older dialysis population.

      Malnutrition-Wasting Conditions

      Older persons even without kidney disease manifest several distinctive phenotypes relating to malnutrition-wasting conditions. These conditions include sarcopenia, dynapenia, PEW, and frailty, with each having been shown to relate to a worse outcome.

      Sarcopenia

Sarcopenia is a reduction in muscle mass. The concept itself is old and, in 1989, Rosenberg [4] defined the condition as the reduction of muscle mass due to advanced age. Since then, it has been broadened to include reduction in muscle mass due to other reasons. One study of 330 incident dialysis patients indicated that a reduction in both muscle mass and strength was associated with worse all-cause 5-year survival (hazard ratio [HR] 1.93; 95%CI 1.01–3.73) [5]. Interestingly, only the reduction in muscle mass was not associated with worse outcome (HR 1.23; 95% CI 0.56–2.67) [5]. This suggests the concept of dynapenia [3] (the age-associated reduction in muscle strength), which may be related to neurologic or muscular function.

      Protein-Energy Wasting

PEW can arise from a wide variety of conditions observed in advanced chronic kidney disease or end-stage renal disease (ESRD) [3]. The co-existence of malnutrition and wasting causes these conditions. Dialysis patients often experience wasting conditions because of inflammation, loss of amino acids into the dialysate, acidemia, endocrinological disorders, and anemia. The International Society of Renal Nutrition and Metabolism defines PEW as “a state of decreased body stores of protein and energy fuels (body protein and fat masses)” [6]. Serum albumin is a key factor in PEW, and low serum albumin or reduction in existing albumin level is associated with worse survival, which suggests that preventing PEW is important in improving survival [7].

      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 СКАЧАТЬ