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Part 7: Nutrition in PD |
Divisions of Baxter Novum and Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Correspondence to: P. Stenvinkel, Karolinska University Hospital at Huddinge, K56, Stockholm 14186 Sweden. peter.stenvinkel{at}ki.se
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ABSTRACT |
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 TOP ABSTRACT ROLE OF INFLAMMATION AND...METHODS TO IDENTIFY PEM/W...MANAGEMENT OF MALNOURISHMENT IN...CONCLUSIONSREFERENCES |
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Protein–energy malnutrition (PEM) is highly prevalent among
peritoneal dialysis (PD) patients and is a strong predictor of morbidity and
mortality. A wide range of factors can lead to PEM and associated wasting
(PEM/W) in PD patients, but persistent inflammation and the presence of
diabetes have been identified as the two main reasons. An important body of
literature has been reporting studies of methods suitable for detecting
malnutrition in its early phase so that appropriate intervention can be
provided. Although assessment of nutrition status has been substantially
improved, no definitive single method of assessing nutrition status has been
decided. Rather, several different markers of nutrition should be evaluated
together. Because of the complexity of treating malnutrition in PD patients,
nontraditional strategies such as appetite stimulants, anti-inflammatory
diets, and anti-inflammatory pharmacologic agents are recommended to be
combined with more traditional forms of nutritional support, so as to provide
a better chance of recovery. The present review briefly discusses the causes
of PEM/W, the methods most commonly used to identify the condition, and the
new management strategies available.
KEY WORDS: Malnutrition; inflammation; diabetes mellitus.
Protein–energy malnutrition and associated wasting (PEM/W) are common in peritoneal dialysis (PD) patients and are a strong predictor of morbidity and mortality. Although various catabolic factors contribute to PEM/W in PD patients (Table 1), inflammation, which is highly prevalent in these patients, may be one of the most important (1). On the other hand, the presence of diabetes mellitus in dialysis patients is well appreciated (2,3) to be another major risk factor for developing protein depletion and loss of lean body mass (LBM). Importantly, the number of incident dialysis patients with diabetes is increasing alarmingly worldwide. Thus, in this review, we briefly discuss the causes of PEM/W (in particular, the roles of inflammation and diabetes) and the methods commonly used to identify the condition. We also propose new strategies to manage malnourishment in this patient group.
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ROLE OF INFLAMMATION AND DIABETES IN PEM/W |
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TOPABSTRACTROLE OF INFLAMMATION AND...METHODS TO IDENTIFY PEM/W...MANAGEMENT OF MALNOURISHMENT IN...CONCLUSIONSREFERENCES |
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(TNF-), and reduced
production of adiponectin (5).
Thus, decreased insulin sensitivity induced by chronic inflammation may cause
loss of muscle mass by reducing the anabolic action of insulin on skeletal
muscle. In fact, Pupim et al.
(3) observed increased muscle
protein breakdown in hemodialysis (HD) patients with type 2 diabetes. Another important mechanism by which inflammation may cause PEM/W is increased resting energy expenditure (REE). The significant correlation between inflammation and increased REE has been demonstrated in dialysis patients and chronic kidney disease (CKD) patients alike (6–8).
Finally, inflammation may also cause PEM/W by suppression of appetite and
eating behavior. Indeed, Aguilera et al.
(9) reported that plasma levels
of TNF- were significantly higher in PD patients with anorexia (or
anorexia with nausea and vomiting) than in PD patients without such symptoms.
The mechanism or mechanisms by which inflammation may cause anorexia are not
understood. However, inflammation may mediate anorexia through the hormone
leptin, which has been demonstrated in animal studies to be upregulated by
proinflammatory cytokines
(10).
Diabetes May Cause PEM/W: The presence of diabetes in dialysis patients has the potential to increase body protein loss and muscle wasting. One important mechanism by which diabetes may cause PEM/W is insulin resistance—the primary mediator of accelerated protein breakdown in dialysis patients (3). Because insulin is an anabolic hormone (insulin deprivation elevates protein breakdown, and insulin elevation blunts protein breakdown), insulin interacts with amino acid availability to regulate protein synthesis. Indeed, in a recent study, HD patients with type 2 diabetes had significantly increased breakdown in skeletal muscle protein as compared with nondiabetic HD patients (3), and CKD patients with diabetes had significantly accelerated loss of LBM as compared with nondiabetic CKD patients during the first year of renal replacement therapy (2).
Another important mechanism by which diabetes may cause PEM/W is increased REE. Previous studies in PD patients (6) and in CKD patients (11) showed that diabetes was an independent risk factor associated with increased REE. In addition, diabetic gastroparesis is more likely to affect protein synthesis related to decreases in consumption, leading to PEM/W.
Glucagon, glucocorticoids, and catecholamines are counter-regulatory hormones whose metabolic role may also counteract protein anabolism. However, the separate effects of each one on nutrition status are not well defined because they are generally concomitantly altered in stressful conditions.
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METHODS TO IDENTIFY PEM/W IN PD PATIENTS |
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TOPABSTRACTROLE OF INFLAMMATION AND...METHODS TO IDENTIFY PEM/W...MANAGEMENT OF MALNOURISHMENT IN...CONCLUSIONSREFERENCES |
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Biochemical Markers: Serum albumin has been, by far, the most commonly used marker of nutrition status in CKD patients, and it is a powerful predictor of mortality in PD patients (12). However, serum albumin levels in PD patients are influenced by several factors. In fact, the low serum albumin level observed in PD patients may reflect mostly the acute-phase response and resulting albumin losses in dialysate and urine, and only to a lesser extent poor nutrition status.
Prealbumin has been shown to be a more sensitive index of nutrition because of its shorter half-life. Moreover, prealbumin has a closer relationship with nutrition status than albumin does, and so it is a good predictor of clinical outcome. However, it should be noted that prealbumin is also a negative acute-phase protein (13).
Plasma amino acid levels are also abnormal in CKD patients, with levels of essential amino acids being low, and levels of nonessential amino acids often being high. Dialysis does not reverse these abnormalities (14).
Estimated Protein Intake: The protein equivalent of nitrogen appearance (PNA) assessed by urea kinetics is an indirect estimate of dietary protein intake (15) and a key measure of nutrition status in dialysis patients. However, this method is influenced by its mathematical coupling with urea kinetics (16), and the correlation between PNA and dietary protein intake is far from perfect because of various factors that influence metabolism, such as dietary protein and energy intake, acidosis, inflammation and infection, and other forms of comorbidity. Furthermore, fecal nitrogen excretion may vary considerably from one patient to the next, although it tends to be constant in an individual patient (15), and unmeasured losses of nitrogen by other routes, such as respiration, sweat, skin desquamation, nail and hair growth, blood sampling, and other blood losses are not taken into account. Finally, normalized PNA (nPNA) by actual weight tends to be high in malnourished underweight PD patients (16). It is therefore recommended that PNA be normalized by desirable body weight instead of by actual body weight.
Assessment of Body Composition: Dual-energy X-ray absorptiometry (DEXA) is considered to be superior to the other easily available methods for determining body composition in CKD, and it has been widely applied for studies of body composition in dialysis patients. With DEXA, bone mineral, fat mass (FM), and LBM distribution are estimated directly, without making assumptions about the two-compartment model. However, the assessment of LBM by DEXA is subject to flaws, because it assumes that 72% of the LBM compartment is water. Given that PD patients can exhibit abnormal hydration status, DEXA might not be a very precise method for assessing LBM in dialyzed patients. Therefore, measurement of LBM by DEXA should be combined with estimation of the extracellular fluid volume by the tracer dilution technique.
Anthropometrics (measurements of actual body weight, height, frame size, and skinfold thickness) are easy to obtain and provide estimates of ideal body weight, body mass index, and other height-to-weight indices. Using anthropometric methods, FM can be obtained from measurements of the four skinfold thicknesses (biceps, triceps, subscapular, and suprailiac) and from calculated body density. By subtracting FM from total body weight, LBM can be indirectly estimated. This estimation of FM and LBM agrees reasonably well with results from DEXA (13). Thus, because anthropometrics are easy and inexpensive to use, this technique can be recommended for routine assessment of nutrition status. However, caution should be exercised regarding interpretation of the results; anthropometrics can be an insensitive method, whose errors include sensitivity to hydration status.
Single- and multi-frequency bioelectrical impedance analysis (BIA) has recently been used in many studies of the nutrition status of dialysis patients. However, the extent to which measured impedance really contributes to the results is not clear; height and body weight have been suggested to be major sources of the variance in BIA prediction models. In addition, and most importantly, assessment of LBM and FM by BIA is greatly influenced by hydration status. Because dialysis patients can exhibit abnormal fluid balance, the accuracy of BIA in the evaluation of body composition in PD patients is being questioned. To reduce error, it is highly recommended that these last three methods (DEXA, anthropometrics, and BIA) be used when dialysis patients are at their edema-free body weight. Thus, the evaluation should be performed with an empty peritoneal cavity or after an HD session.
Creatinine kinetics is another method that has been used to calculate LBM in PD patients. The method is based on creatinine excretion in urine and dialysate. However, the LBM estimated from creatinine kinetics is usually markedly lower than that estimated by methods such as total body potassium (17), anthropometry (18), and DEXA (18). Furthermore, LBM estimated from creatinine kinetics depends on the creatinine content in the diet (mainly related to meat consumption), and the metabolic degradation of creatinine, which is poorly understood in uremia. Finally, the variation observed during repeated measures of LBM estimated using creatinine kinetics is unacceptably high (17). Creatinine kinetics is therefore not considered a valid method for monitoring LBM in PD patients.
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MANAGEMENT OF MALNOURISHMENT IN PD PATIENTS |
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TOPABSTRACTROLE OF INFLAMMATION AND...METHODS TO IDENTIFY PEM/W...MANAGEMENT OF MALNOURISHMENT IN...CONCLUSIONSREFERENCES |
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Amino Acid–Based PD Fluids: The use of PD solutions containing amino acids may have some nutritional advantages for PD patients. The involuntary intake of amino acids from the dialysate could overcome the protein losses that normally occur during the PD procedure. That intake may, in turn, result in a positive nitrogen balance, a significant increase in net protein anabolism, and a significant increase in serum total protein and transferrin.
In fact, in a prospective, randomized, open-label study that evaluated the role of amino-acid dialysate on the nutrition status of malnourished PD patients, patients who replaced 1 daily exchange of traditional dialysate with amino-acid dialysate showed better evolution in markers of nutrition than did patients who continued to use dextrose dialysate only (19). Those positive findings were also replicated in another randomized study (20).
Appetite Stimulants: The use of appetite stimulants such as megestrol acetate, cannabinoids, and cyproheptadine may be a tempting part of a new strategy for malnourished PD patients. Megestrol acetate has been suggested for use as an appetite stimulant in HD and PD patients (21,22); however, it is associated with several side effects, including hypogonadism, impotence, and increased risk of thromboembolism. Thus, the treatment must be monitored closely, and results of controlled, prospective, randomized trials must be awaited.
Diets with Anti-inflammatory Potential: Given that the phytoestrogen genistein is effective in blocking inflammatory gene expression (23) and dietary phytoestrogens contained in soybeans may have significant anti-inflammatory properties, consumption phytoestrogens may be of value in PD patients. In fact, a recent study with HD patients suggested a trend toward a reduction in the serum concentration of C-reactive protein (CRP) after 8 weeks' ingestion of an isoflavone soy-based supplement (24). However, additional studies to confirm this finding in PD patients are still necessary.
The importance of dietary fiber is underscored by a recent evaluation study demonstrating that high fiber consumption in non-renal subjects lowered the risk of elevated CRP (25). The anti-inflammatory effects of the omega-3 fatty acids, mainly eicosapentaenoic acid, found in fish oil are well recognized. Indeed, dietary fish oil reduces levels of CRP and interleukin-6 in non-renal subjects (26).
Although reduced renal clearance and increased oxidative stress may be the most important causes of high levels of advanced glycation end-products (AGEs) in CKD patients, diet may be a significant source of highly reactive AGEs. Indeed, Uribarri et al. (27) showed that dietary glycotoxins contribute to significantly elevated AGE levels in CKD patients. Importantly, a reduction in dietary AGE content can be achieved safely without compromising the content of vital nutrients such as dietary protein, fat, and carbohydrates (28).
Anti-inflammatory Pharmacologic Treatment: In CKD patients, strong
associations have been found between proinflammatory cytokines and PEM/W.
Various pharmacologic treatment strategies with anti-inflammatory effects have
therefore been proposed for those patients
(29), including HMG–CoA
(3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors (statins),
angiotensin converting-enzyme inhibitors, peroxisome proliferator-activated
receptor agonists, and anti-oxidative agents, such as - and
-tocopherol.
Anti-cytokine Treatment: Targeted anti-cytokine treatment strategies may also be of interest in CKD patients. Indeed, central administration of specific interleukin-1 receptor antagonist attenuated some (but not all) of the metabolic responses secondary to systemic infection and endotoxins, and prevented sepsis-induced inhibition of protein synthesis in rats (30). However, given available toxicity data, clinicians should exercise caution regarding the use of these agents until large randomized trials have been conducted to prove their efficacy and safety in this patient group.
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CONCLUSIONS |
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TOPABSTRACTROLE OF INFLAMMATION AND...METHODS TO IDENTIFY PEM/W...MANAGEMENT OF MALNOURISHMENT IN...CONCLUSIONSREFERENCES |
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REFERENCES |
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TOPABSTRACTROLE OF INFLAMMATION AND...METHODS TO IDENTIFY PEM/W...MANAGEMENT OF MALNOURISHMENT IN...CONCLUSIONSREFERENCES |
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, cholecystokinin) and orexigen
(neuropeptide Y) plasma levels in peritoneal dialysis (PD) patients: their
relationship with nutritional parameters. Nephrol Dial
Transplant 1998; 13:1476
-83.
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