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Etiology of the Protein-Energy Wasting Syndrome in Chronic Kidney Disease: A Consensus Statement From the International Society of Renal Nutrition and Metabolism (ISRNM)
2013; Elsevier BV; Volume: 23; Issue: 2 Linguagem: Inglês
10.1053/j.jrn.2013.01.001
ISSN1532-8503
AutoresJuan Jesús Carrero, Peter Stenvinkel, Lílian Cuppari, T. Alp İkizler, Kamyar Kalantar‐Zadeh, George A. Kaysen, William E. Mitch, S. Russ Price, Christoph Wanner, Angela Yee‐Moon Wang, Pieter ter Wee, Harold A. Franch,
Tópico(s)Muscle and Compartmental Disorders
ResumoProtein-energy wasting (PEW), a term proposed by the International Society of Renal Nutrition and Metabolism (ISRNM), refers to the multiple nutritional and catabolic alterations that occur in chronic kidney disease (CKD) and associate with morbidity and mortality. To increase awareness, identify research needs, and provide the basis for future work to understand therapies and consequences of PEW, ISRNM provides this consensus statement of current knowledge on the etiology of PEW syndrome in CKD. Although insufficient food intake (true undernutrition) due to poor appetite and dietary restrictions contribute, other highly prevalent factors are required for the full syndrome to develop. These include uremia-induced alterations such as increased energy expenditure, persistent inflammation, acidosis, and multiple endocrine disorders that render a state of hypermetabolism leading to excess catabolism of muscle and fat. In addition, comorbid conditions associated with CKD, poor physical activity, frailty, and the dialysis procedure per se further contribute to PEW. Protein-energy wasting (PEW), a term proposed by the International Society of Renal Nutrition and Metabolism (ISRNM), refers to the multiple nutritional and catabolic alterations that occur in chronic kidney disease (CKD) and associate with morbidity and mortality. To increase awareness, identify research needs, and provide the basis for future work to understand therapies and consequences of PEW, ISRNM provides this consensus statement of current knowledge on the etiology of PEW syndrome in CKD. Although insufficient food intake (true undernutrition) due to poor appetite and dietary restrictions contribute, other highly prevalent factors are required for the full syndrome to develop. These include uremia-induced alterations such as increased energy expenditure, persistent inflammation, acidosis, and multiple endocrine disorders that render a state of hypermetabolism leading to excess catabolism of muscle and fat. In addition, comorbid conditions associated with CKD, poor physical activity, frailty, and the dialysis procedure per se further contribute to PEW. IntroductionA syndrome of adverse changes in nutrition and body composition is highly prevalent in patients with chronic kidney disease (CKD), especially in those undergoing dialysis, and it is associated with high morbidity and mortality. A summary of the mechanisms involved in these alterations is provided in Figure 1. Although insufficient food intake (true undernutrition) due to poor appetite and dietary restrictions contributes to these problems, there are features of the syndrome that cannot be explained by undernutrition alone. Many contributing causes are directly related to kidney disease, including increased resting energy expenditure (REE), persistent inflammation, acidosis, multiple endocrine disorders, and the dialysis procedure itself. However, this syndrome shares etiologic factors that contribute to cachexia in non-CKD populations, including comorbid conditions associated with cachexia, decreased physical activity, frailty, and aging. The CKD and end-stage renal disease (ESRD) populations are unique in the constant surveillance that facilitates the diagnosis of wasting before frank cachexia begins. Given the unique features of the syndrome, the International Society of Renal Nutrition and Metabolism (ISRNM) proposed a common nomenclature and diagnostic criteria for these alterations in the context of CKD.1Fouque D. Kalantar-Zadeh K. Kopple J. Cano N. Chauveau P. Cuppari L. et al.A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease.Kidney Int. 2008; 73: 391-398Crossref PubMed Scopus (349) Google Scholar Protein-energy wasting (PEW) was proposed to denote concurrent losses in protein and energy stores, with cachexia being regarded as only the end stage. ISRNM's intention was to begin creating a framework to identify and understand disorders that promote PEW.2Hoffer L.J. The need for consistent criteria for identifying malnutrition.Nestle Nutr Workshop Ser Clin Perform Programme. 2009; 12: 41-52Crossref PubMed Scopus (5) Google Scholar To further this process, the ISRNM now provides a consensus review of current knowledge on the etiology of PEW in kidney disease (Table 1) to provide a basis for future advances in diagnosis and therapy and to identify gaps in knowledge for future research.Table 1Causes of PEW in CKD Patients1.Decreased protein and energy intakea.Anorexiai.Dysregulation in circulating appetite mediatorsii.Hypothalamic amino acid sensingiii.Nitrogen-based uremic toxinsb.Dietary restrictionsc.Alterations in organs involved in nutrient intaked.Depressione.Inability to obtain or prepare food2.Hypermetabolisma.Increased energy expenditurei.Inflammationii.Increased circulating proinflammatory cytokinesiii.Insulin resistance secondary to obesityiv.Altered adiponectin and resistin metabolismb.Hormonal disordersi.Insulin resistance of CKDii.Increased glucocorticoid activity3.Metabolic acidosis4.Decreased physical activity5.Decreased anabolisma.Decreased nutrient intakeb.Resistance to GH/IGF-1c.Testosterone deficiencyd.Low thyroid hormone levels6.Comorbidities and lifestylea.Comorbidities (diabetes mellitus, CHF, depression, coronary artery disease, peripheral vascular disease)7.Dialysisa.Nutrient losses into dialysateb.Dialysis-related inflammationc.Dialysis-related hypermetabolismd.Loss of residual renal function Open table in a new tab Undernutrition and AnorexiaLow energy and/or protein intake associates with a significant decline of nutritional parameters (including hypoalbuminemia) and increased risk of morbidity and mortality in patients with advanced CKD.3Araujo I.C. Kamimura M.A. Draibe S.A. Canziani M.E. Manfredi S.R. Avesani C.M. et al.Nutritional parameters and mortality in incident hemodialysis patients.J Ren Nutr. 2006; 16: 27-35Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 4Kalantar-Zadeh K. Supasyndh O. Lehn R.S. McAllister C.J. Kopple J.D. Normalized protein nitrogen appearance is correlated with hospitalization and mortality in hemodialysis patients with kt/v greater than 1.20.J Ren Nutr. 2003; 13: 15-25Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar In most of these studies, dietary energy and protein intakes are lower than recommended for patients undergoing either hemodialysis (HD)3Araujo I.C. Kamimura M.A. Draibe S.A. Canziani M.E. Manfredi S.R. Avesani C.M. et al.Nutritional parameters and mortality in incident hemodialysis patients.J Ren Nutr. 2006; 16: 27-35Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 5Bossola M. Muscaritoli M. Tazza L. Panocchia N. Liberatori M. Giungi S. et al.Variables associated with reduced dietary intake in hemodialysis patients.J Ren Nutr. 2005; 15: 244-252Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 6Burrowes J.D. Larive B. Chertow G.M. Cockram D.B. Dwyer J.T. Greene T. et al.Self-reported appetite, hospitalization and death in haemodialysis patients: findings from the hemodialysis (HEMO) study.Nephrol Dial Transpl. 2005; 20: 2765-2774Crossref PubMed Scopus (55) Google Scholar or peritoneal dialysis (PD).7Bazanelli A.P. Kamimura M.A. da Silva C.B. Avesani C.M. Lopes M.G. Manfredi S.R. et al.Resting energy expenditure in peritoneal dialysis patients.Perit Dial Int. 2006; 26: 697-704PubMed Google Scholar, 8Wang A.Y. Sea M.M. Ng K. Kwan M. Lui S.F. Woo J. Nutrient intake during peritoneal dialysis at the Prince of Wales Hospital in Hong Kong.Am J Kidney Dis. 2007; 49: 682-692Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar However, dietary recalls underestimate dietary intake,9Kloppenburg W.D. de Jong P.E. Huisman R.M. The contradiction of stable body mass despite low reported dietary energy intake in chronic haemodialysis patients.Nephrol Dial Transpl. 2002; 17: 1628-1633Crossref PubMed Google Scholar, 10Bazanelli A.P. Kamimura M.A. Vasselai P. Draibe S.A. Cuppari L. Underreporting of energy intake in peritoneal dialysis patients.J Ren Nutr. 2010; 20: 263-269Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 11Huang X. Sjogren P. Cederholm T. Arnlov J. Lindholm B. Riserus U. et al.Serum and adipose tissue fatty acid composition as biomarkers of habitual dietary fat intake in elderly men with chronic kidney disease.Nephrol Dial Transpl. 2012; (Available at:) (Accessed January 29, 2013)http://ndt.oxfordjournals.org/content/early/2012/12/09/ndt.gfs478.longGoogle Scholar and improving accuracy of dietary monitoring is needed. There is presently limited information correlating dietary composition, including micro/macronutrient intake, with outcomes.12Huang X. Stenvinkel P. Qureshi A.R. Cederholm T. Barany P. Heimburger O. et al.Clinical determinants and mortality predictability of stearoyl-coa desaturase-1 activity indices in dialysis patients.J Intern Med. 2012 Aug 17; ([Epub ahead of print])https://doi.org/10.1111/j.1365-2796.2012.02573.xCrossref Scopus (6) Google Scholar, 13Huang X. Stenvinkel P. Qureshi A.R. Riserus U. Cederholm T. Barany P. et al.Essential polyunsaturated fatty acids, inflammation and mortality in dialysis patients.Nephrol Dial Transpl. 2012; 27: 3615-3620Crossref PubMed Scopus (12) Google Scholar, 14Jankowska M. Marszall M. Debska-Slizien A. Carrero J.J. Lindholm B. Czarnowski W. et al.Vitamin B6 and the immunity in kidney transplant recipients.J Ren Nutr. 2013; 23: 57-64Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar In one study that was based on food-frequency questionnaires, HD patients consume significantly lower amounts of potassium, dietary fiber, vitamin C, and certain cardioprotective carotenoids.15Kalantar-Zadeh K. Kopple J.D. Deepak S. Block D. Block G. Food intake characteristics of hemodialysis patients as obtained by food frequency questionnaire.J Ren Nutr. 2002; 12: 17-31Abstract Full Text Full Text PDF PubMed Google Scholar Data from the Third National Health and Nutrition Examination Survey showed that high dietary total fiber intake was associated with lower risk of inflammation and mortality in CKD patients.16Krishnamurthy V.M. Wei G. Baird B.C. Murtaugh M. Chonchol M.B. Raphael K.L. et al.High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease.Kidney Int. 2012; 81: 300-306Crossref PubMed Scopus (20) Google Scholar Many of the restrictions in renal diets contradict current recommendations for healthy eating. Although limiting dietary sodium, phosphate, potassium, and fluid intake prevents important patient complications, problems arise when these restrictions are not accompanied with appropriate counseling on alternative food choices and/or strategies to ensure adequate nutrient intake.17Hollingdale R. Sutton D. Hart K. Facilitating dietary change in renal disease: investigating patients' perspectives.J Ren Care. 2008; 34: 136-142Crossref PubMed Scopus (10) Google Scholar, 18Paes-Barreto J.G. Barreto Silva M.I. Qureshi A.R. Bregman R. Cervante V.F. Carrero J.J. et al.Can renal nutrition education improve adherence to a low-protein diet in patients with stages 3 to 5 chronic kidney disease?.J Ren Nutr. 2012; (Available at:) (Accessed January 29, 2013)http://www.jrnjournal.org/article/S1051-2276(12)00203-8/abstractPubMed Google ScholarAnorexia often drives inadequate protein and energy intake and directly contributes to poor quality of life.6Burrowes J.D. Larive B. Chertow G.M. Cockram D.B. Dwyer J.T. Greene T. et al.Self-reported appetite, hospitalization and death in haemodialysis patients: findings from the hemodialysis (HEMO) study.Nephrol Dial Transpl. 2005; 20: 2765-2774Crossref PubMed Scopus (55) Google Scholar, 19Carrero J.J. Qureshi A.R. Axelsson J. Avesani C.M. Suliman M.E. Kato S. et al.Comparison of nutritional and inflammatory markers in dialysis patients with reduced appetite.Am J Clin Nutr. 2007; 85: 695-701PubMed Google Scholar, 20Kalantar-Zadeh K. Block G. McAllister C.J. Humphreys M.H. Kopple J.D. Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients.Am J Clin Nutr. 2004; 80: 299-307PubMed Google Scholar, 21Lopes A.A. Elder S.J. Ginsberg N. Andreucci V.E. Cruz J.M. Fukuhara S. et al.Lack of appetite in haemodialysis patients—associations with patient characteristics, indicators of nutritional status and outcomes in the international DOPPS.Nephrol Dial Transpl. 2007; 22: 3538-3546Crossref PubMed Scopus (41) Google Scholar The prevalence of anorexia has been reported at 35% to 50% of ESRD patients.22Bossola M. Tazza L. Giungi S. Luciani G. Anorexia in hemodialysis patients: an update.Kidney Int. 2006; 70: 417-422Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 23Carrero J.J. Identification of patients with eating disorders: clinical and biochemical signs of appetite loss in dialysis patients.J Ren Nutr. 2009; 19: 10-15Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Although few studies exist in CKD stages 1-3, a progressive, spontaneous decrease in food intake occurs with greater loss of kidney function, which correlates with accumulation of nitrogen-derived uremic toxins.24Kopple J.D. Berg R. Houser H. Steinman T.I. Teschan P. Nutritional status of patients with different levels of chronic renal insufficiency. Modification of diet in renal disease (MDRD) study group.Kidney Int Suppl. 1989; 27: S184-S194PubMed Google Scholar, 25Duenhas M.R. Draibe S.A. Avesani C.M. Sesso R. Cuppari L. Influence of renal function on spontaneous dietary intake and on nutritional status of chronic renal insufficiency patients.Eur J Clin Nutr. 2003; 57: 1473-1478Crossref PubMed Scopus (17) Google Scholar, 26Ikizler T.A. Greene J.H. Wingard R.L. Parker R.A. Hakim R.M. Spontaneous dietary protein intake during progression of chronic renal failure.J Am Soc Nephrol. 1995; 6: 1386-1391PubMed Google Scholar The factors influencing food intake involve not only metabolic signals but also anomalies in the digestive system and psychological and acquired aspects, including a desire for pleasure, social behavior, and customs.27Carrero J.J. Mechanisms of altered regulation of food intake in chronic kidney disease.J Ren Nutr. 2011; 21: 7-11Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Anorexia may be mediated by circulating appetite regulators, such as gastric mediators (such as cholecystokinin,28Wright M. Woodrow G. O'Brien S. Armstrong E. King N. Dye L. et al.Cholecystokinin and leptin: their influence upon the eating behaviour and nutrient intake of dialysis patients.Nephrol Dial Transpl. 2004; 19: 133-140Crossref PubMed Scopus (25) Google Scholar peptide YY,29Perez-Fontan M. Cordido F. Rodriguez-Carmona A. Penin M. Diaz-Cambre H. Lopez-Muniz A. et al.Short-term regulation of peptide YY secretion by a mixed meal or peritoneal glucose-based dialysate in patients with chronic renal failure.Nephrol Dial Transpl. 2008; 23: 3696-3703Crossref PubMed Scopus (13) Google Scholar ghrelin,30Muscaritoli M. Molfino A. Chiappini M.G. Laviano A. Ammann T. Spinsanti P. et al.Anorexia in hemodialysis patients: the possible role of des-acyl ghrelin.Am J Nephrol. 2007; 27: 360-365Crossref PubMed Scopus (39) Google Scholar, 31Carrero J.J. Nakashima A. Qureshi A.R. Lindholm B. Heimburger O. Barany P. et al.Protein-energy wasting modifies the association of ghrelin with inflammation, leptin, and mortality in hemodialysis patients.Kidney Int. 2011; 79: 749-756Crossref PubMed Scopus (22) Google Scholar or obestatin), adipokines (such as leptin32Cheung W. Yu P.X. Little B.M. Cone R.D. Marks D.L. Mak R.H. Role of leptin and melanocortin signaling in uremia-associated cachexia.J Clin Invest. 2005; 115: 1659-1665Crossref PubMed Scopus (150) Google Scholar and visfatin33Carrero J.J. Witasp A. Stenvinkel P. Qureshi A.R. Heimburger O. Barany P. et al.Visfatin is increased in chronic kidney disease patients with poor appetite and correlates negatively with fasting serum amino acids and triglyceride levels.Nephrol Dial Transpl. 2010; 25: 901-906Crossref PubMed Scopus (22) Google Scholar), or cytokines (such as tumor necrosis factor [TNF], interleukin [IL]-6, and IL-1β19Carrero J.J. Qureshi A.R. Axelsson J. Avesani C.M. Suliman M.E. Kato S. et al.Comparison of nutritional and inflammatory markers in dialysis patients with reduced appetite.Am J Clin Nutr. 2007; 85: 695-701PubMed Google Scholar, 20Kalantar-Zadeh K. Block G. McAllister C.J. Humphreys M.H. Kopple J.D. Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients.Am J Clin Nutr. 2004; 80: 299-307PubMed Google Scholar), but these mediators need additional research in the uremic milieu.34Carrero J.J. Stenvinkel P. Nutrition: Can ghrelin improve appetite in uremic wasting?.Nat Rev Nephrol. 2009; 5: 672-673Crossref PubMed Scopus (8) Google Scholar Signaling by hypothalamic neurons that sense the ratio of essential to nonessential amino acids35Bossola M. Scribano D. Colacicco L. Tavazzi B. Giungi S. Zuppi C. et al.Anorexia and plasma levels of free tryptophan, branched chain amino acids, and ghrelin in hemodialysis patients.J Ren Nutr. 2009; 19: 248-255Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar may be influenced by the fall in branched-chain amino acid levels with uremia or dialysis, creating the so-called brain hyperserotoninergic-like syndrome. The role of other complications of uremia on anorexia need to be further explored, including dental and oral problems (such as palatability problems or incidence of periodontitis36Akar H. Akar G.C. Carrero J.J. Stenvinkel P. Lindholm B. Systemic consequences of poor oral health in chronic kidney disease patients.Clin J Am Soc Nephrol. 2011; 6: 218-226Crossref PubMed Scopus (17) Google Scholar), gastric alterations37Bossola M. Luciani G. Rosa F. Tazza L. Appetite and gastrointestinal symptoms in chronic hemodialysis patients.J Ren Nutr. 2011; 21: 448-454Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar (motility disorders,38Aguilera A. Bajo M.A. Espinoza M. Olveira A. Paiva A.M. Codoceo R. et al.Gastrointestinal and pancreatic function in peritoneal dialysis patients: their relationship with malnutrition and peritoneal membrane abnormalities.Am J Kidney Dis. 2003; 42: 787-796Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar dyspepsia,39Van Vlem B. Schoonjans R. Vanholder R. De Vos M. Vandamme W. Van Laecke S. et al.Delayed gastric emptying in dyspeptic chronic hemodialysis patients.Am J Kidney Dis. 2000; 36: 962-968Abstract Full Text Full Text PDF PubMed Google Scholar or bacterial infections in the intestine40Aguilera A. Gonzalez-Espinoza L. Codoceo R. Jara Mdel C. Pavone M. Bajo M.A. et al.Bowel bacterial overgrowth as another cause of malnutrition, inflammation, and atherosclerosis syndrome in peritoneal dialysis patients.Adv Perit Dial. 2010; 26: 130-136PubMed Google Scholar), and depression.21Lopes A.A. Elder S.J. Ginsberg N. Andreucci V.E. Cruz J.M. Fukuhara S. et al.Lack of appetite in haemodialysis patients—associations with patient characteristics, indicators of nutritional status and outcomes in the international DOPPS.Nephrol Dial Transpl. 2007; 22: 3538-3546Crossref PubMed Scopus (41) Google Scholar, 41Hung K.C. Wu C.C. Chen H.S. Ma W.Y. Tseng C.F. Yang L.K. et al.Serum IL-6, albumin and co-morbidities are closely correlated with symptoms of depression in patients on maintenance haemodialysis.Nephrol Dial Transpl. 2011; 26: 658-664Crossref PubMed Scopus (16) Google ScholarAlthough reduced intake of food or poor absorption of nutrients plays a critical role in most cases of PEW,42Evans W.J. Morley J.E. Argiles J. Bales C. Baracos V. Guttridge D. et al.Cachexia: a new definition.Clin Nutr (Edinburgh, Scotland). 2008; 27: 793-799Abstract Full Text Full Text PDF PubMed Scopus (478) Google Scholar, 43Morley J.E. Thomas D.R. Cachexia: new advances in the management of wasting diseases.J Am Med Dir Assoc. 2008; 9: 205-210Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar the science of starvation suggests that additional mechanisms are needed for PEW to occur (Fig. 2). Decreased energy intake reduces insulin secretion and stimulates the production of sugar from glycogen and increased mobilization of fatty acids.44Shetty P.S. Adaptation to low energy intakes: the responses and limits to low intakes in infants, children and adults.Eur J Clin Nutr. 1999; 53: S14-S33Crossref PubMed Google Scholar Activation of these systems contributes to a reduction in basal metabolic rate and mobilization of free fatty acids and amino acids.44Shetty P.S. Adaptation to low energy intakes: the responses and limits to low intakes in infants, children and adults.Eur J Clin Nutr. 1999; 53: S14-S33Crossref PubMed Google Scholar, 45Emery P.W. Metabolic changes in malnutrition.Eye. 2005; 19: 1029-1034Crossref PubMed Scopus (16) Google Scholar Muscle proteolysis only transiently increases in early starvation, but muscle release of amino acids declines over the first 2 weeks of starvation and visceral organ proteins are used preferentially to muscle.46Waterlow J.C. Garlick P.J. Millward D.J. Protein turnover in mammalian tissues and in the whole body. North Holland, Amsterdam, The Netherlands1978Google Scholar Muscle and visceral proteins can be preserved to some extent because of heightened insulin sensitivity, and diets with as little as 0.55 g/kg/day of balanced protein may be well tolerated.47Franch H.A. Mitch W.E. Navigating between the scylla and charybdis of prescribing dietary protein for chronic kidney diseases.Annu Rev Nutr. 2009; 29: 341-364Crossref PubMed Scopus (9) Google Scholar Below that level, the loss of visceral protein and increases in lipolysis lead to fatty infiltration of the liver and decreased plasma protein synthesis.48Golden M.H. The development of concepts of malnutrition.J Nutr. 2002; 132: 2117S-2122SPubMed Google Scholar However, plasma proteins, particularly prealbumin and S-albumin, have increased half-life and do not change in concentration with moderate calorie or protein restriction alone.49Don B.R. Kaysen G. Serum albumin: relationship to inflammation and nutrition.Semin Dial. 2004; 17: 432-437Crossref PubMed Scopus (152) Google Scholar, 50Myron Johnson A. Merlini G. Sheldon J. Ichihara K. Clinical indications for plasma protein assays: transthyretin (prealbumin) in inflammation and malnutrition.Clin Chem Lab Med. 2007; 45: 419-426Crossref PubMed Scopus (48) Google Scholar Generally, other factors in addition to starvation (especially inflammation and acidosis) are required for accelerated muscle loss and hypoalbuminemia. However, depletion of visceral protein stores caused by prolonged decreased energy intake or frequent intermittent starvation causes disruption of certain protective mechanisms. Heavy ketone body formation marks a transition in metabolism to more severe starvation and causes a loss of the adaptation that prevented hypoalbuminemia and limited muscle wasting earlier in starvation.44Shetty P.S. Adaptation to low energy intakes: the responses and limits to low intakes in infants, children and adults.Eur J Clin Nutr. 1999; 53: S14-S33Crossref PubMed Google Scholar, 51Finn P.F. Dice J.F. Proteolytic and lipolytic responses to starvation.Nutrition. 2006; 22: 830-844Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar The acid and the ketone bodies in severe starvation appear to be critical in making protein loss from muscle greater than from other organs and making amino acids a critical source of glucose.46Waterlow J.C. Garlick P.J. Millward D.J. Protein turnover in mammalian tissues and in the whole body. North Holland, Amsterdam, The Netherlands1978Google ScholarFigure 2Response to reduced dietary protein and energy intake. (A) Normal response. Reduced dietary protein and energy drive an increase in hunger and a fall in REE, loss of protein preferentially from the visceral organs, and increased insulin sensitivity of muscle. The liver and kidney provide glucose, and serum albumin is maintained at a normal level. (B) Response with PEW. During PEW, the adaptations to increase hunger and lower REE are blunted in part by an increased half-life of leptin and ghrelin and in part by inflammation and dialysis. The loss of protein occurs preferentially from muscle because of the effects of metabolic acidosis, glucocorticoids, and inflammation, leading to increased insulin resistance. Dialysis results in the loss of amino acids, stimulating muscle protein breakdown. Under the influence of inflammation and metabolic acidosis, the liver makes glutamine for deamination in the kidney, increases acute-phase reactants, and reduces serum albumin. The kidney increases glucose production from glutamine under the influence of metabolic acidosis.View Large Image Figure ViewerDownload Hi-res image Download (PPT)HypermetabolismIncreased Energy ExpenditureIn simple starvation, the body reduces energy expenditure to conserve energy needs. REE is usually normal in stable maintenance dialysis or CKD patients. In contrast, REE increases from 12% to 20% in CKD patients during the HD procedure52Neyra R. Chen K.Y. Sun M. Shyr Y. Hakim R.M. Ikizler T.A. Increased resting energy expenditure in patients with end-stage renal disease.JPEN J Parenter Enteral Nutr. 2003; 27: 36-42Crossref PubMed Google Scholar or in the presence of comorbidities such as cardiovascular disease (CVD),53Wang A.Y. Sea M.M. Tang N. Sanderson J.E. Lui S.F. Li P.K. et al.Resting energy expenditure and subsequent mortality risk in peritoneal dialysis patients.J Am Soc Nephrol. 2004; 15: 3134-3143Crossref PubMed Scopus (58) Google Scholar severe hyperparathyroidism,54Cuppari L. de Carvalho A.B. Avesani C.M. Kamimura M.A. Dos Santos Lobao R.R. Draibe S.A. Increased resting energy expenditure in hemodialysis patients with severe hyperparathyroidism.J Am Soc Nephrol. 2004; 15: 2933-2939Crossref PubMed Scopus (31) Google Scholar poorly controlled diabetes,55Avesani C.M. Cuppari L. Silva A.C. Sigulem D.M. Cendoroglo M. Sesso R. et al.Resting energy expenditure in pre-dialysis diabetic patients.Nephrol Dial Transpl. 2001; 16: 556-565Crossref PubMed Google Scholar inflammation, PEW,53Wang A.Y. Sea M.M. Tang N. Sanderson J.E. Lui S.F. Li P.K. et al.Resting energy expenditure and subsequent mortality risk in peritoneal dialysis patients.J Am Soc Nephrol. 2004; 15: 3134-3143Crossref PubMed Scopus (58) Google Scholar, 56Utaka S. Avesani C.M. Draibe S.A. Kamimura M.A. Andreoni S. Cuppari L. Inflammation is associated with increased energy expenditure in patients with chronic kidney disease.Am J Clin Nutr. 2005; 82: 801-805PubMed Google Scholar, 57Kamimura M.A. Draibe S.A. Dalboni M.A. Cendoroglo M. Avesani C.M. Manfredi S.R. et al.Serum and cellular interleukin-6 in haemodialysis patients: relationship with energy expenditure.Nephrol Dial Transpl. 2007; 22: 839-844Crossref PubMed Scopus (23) Google Scholar and loss of residual kidney function.53Wang A.Y. Sea M.M. Tang N. Sanderson J.E. Lui S.F. Li P.K. et al.Resting energy expenditure and subsequent mortality risk in peritoneal dialysis patients.J Am Soc Nephrol. 2004; 15: 3134-3143Crossref PubMed Scopus (58) Google Scholar In PD patients, PEW was more frequent among patients in the highest tertile of REE when compared with those in the lower tertile.53Wang A.Y. Sea M.M. Tang N. Sanderson J.E. Lui S.F. Li P.K. et al.Resting energy expenditure and subsequent mortality risk in peritoneal dialysis patients.J Am Soc Nephrol. 2004; 15: 3134-3143Crossref PubMed Scopus (58) Google Scholar Because protein catabolism and inflammation result in elevated energy expenditure,58Ikizler T.A. Pupim L.B. Brouillette J.R. Levenhagen D.K. Farmer K. Hakim R.M. et al.Hemodialysis stimulates muscle and whole body protein loss and alters substrate oxidation.Am J Physiol Endocrinol Metab. 2002; 282: E107-E116PubMed Google Scholar higher energy intake alone should not correct increased REE under these circumstances (although this has not been rigorously tested). Increased REE is frequently mitigated by decreased physical activity, leading to a reduction, rather than an increase, in total energy expenditure in some studies.59Mafra D. Deleaval P. Teta D. Cleaud C. Arkouche W. Jolivot A. et al.Influence of inflammation on total energy expenditure in hemodialysis patients.J Ren Nutr. 2011; 21: 387-393Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar, 60Avesani C.M. Trolonge S. Deleaval P. Baria F. Mafra D. Faxen-Irving G. et al.Physical activity and energy expenditure in haemodialysis patients: an international survey.Nephrol Dial Transpl. 2012; 27: 2430-2434Crossref PubMed Scopus (7) Google ScholarPersistent InflammationInflammation overcomes the adaptive responses protecting muscle and reducing REE during decreased protein and energy intake. Inflammation activates intracellular NADPH oxidases, creating signals that induce muscle insulin resistance.61Spindler S.R. Caloric restriction: from soup to nuts.Ageing Res Rev. 2010; 9: 324-353Crossref PubMed Scopus (49) Google Scholar The inflammatory response is associated with a rise in REE, which can be so severe that starvation responses are activated in well-fed individuals.44Shetty P.S. Adaptation to low energy intakes: the responses and limits to low intakes in infants, children and adults.Eur J Clin Nutr. 1999; 53: S14-S33Crossref PubMed Google Scholar, 61Spindler S.R. Caloric restriction: from soup to nuts.Ageing Res Rev. 2010; 9: 324-353Crossref PubMed Scopus (49) Google Scholar In
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