Assessment of Body Protein: Energy Status in Chronic Kidney Disease

Assessment of Body Protein: Energy Status in Chronic Kidney Disease Noël J. M. Cano, MD, PhD,*,†,‡,§ Magalie Miolane-Debouit, MD,* Julie Léger, MD,* and Anne-Elizabeth Heng, MD储

Summary: The prevalence of protein-energy malnutrition progressively increases during the evolution of chronic kidney disease (CKD). As a consequence, it has been reported that 40% of patients present with symptoms of undernutrition at the entrance to chronic dialysis treatment. In patients established on maintenance hemodialysis, the prevalence of malnutrition varies from 20% to 60% according to which indicators of nutritional status are used. Protein-energy malnutrition is associated with an increase in overall and cardiovascular death risks both in CKD patients not yet on dialysis and in dialysis patients. Given the impact of protein-energy wasting on the outcome of CKD patients, screening malnutrition and monitoring protein-energy status appear of primary importance. Therefore, scientific and professional societies or foundations have developed guidelines for the assessment of nutritional status as well as for the treatment of malnourished CKD patients. Recently, an expert panel recommended the term protein-energy wasting for loss of body protein mass and fuel reserves. According to these recommendations, protein-energy wasting should be diagnosed if 3 characteristics are present (low serum levels of albumin, transthyretin, or cholesterol), reduced body mass (low or reduced body mass or fat mass or weight loss with reduced intake of protein and energy), and reduced muscle mass (muscle wasting or sarcopenia, reduced mid–arm-muscle circumference). The present article addresses the methods for assessing protein-energy status, their specificities regarding the CKD staging, and the criteria for choosing among these methods when managing the follow-up evaluation of CKD patients. The practical implications of nutritional parameters for the management of CKD patients are illustrated by a case presentation. Semin Nephrol 29:59-66 © 2009 Elsevier Inc. All rights reserved. Keywords: Renal failure, chronic kidney disease, protein energy status, protein energy wasting, nutrition, nutritional status, nutritional assessment, hemodialysis

hronic kidney disease (CKD) is widespread throughout the world. Its estimated prevalence varies from 10% to 20% according to countries and tools used for

C

*CHU Clermont-Ferrand, Service de Nutrition, Hôpital G Montpied, ClermontFerrand, France. †Univ Clermont 1, UFR Médecine, UMR Nutrition Humaine, Clermont-Ferrand, France. ‡CRNH Auvergne, Clermont-Ferrand, France. §Inra, UMR 1019 Nutrition Humaine, Saint Genès Champanelle, France. 储CHU Clermont-Ferrand, Service de Néphrologie, Hôpital G Montpied, Clermont-Ferrand, France. Address reprint requests to Professor Noël J. M. Cano, MD, PhD, Centre de Recherche en Nutrition Humaine d’Auvergne, 58 Rue Montalembert, F-63009, Clermont-Ferrand, France. E-mail: [email protected] 0270-9295/09/$ - see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.semnephrol.2008.10.008

CKD detection.1-5 Similarly, the number of patients requiring chronic routine dialysis treatment is increasing continuously. In the United States, the number of patients treated by maintenance hemodialysis is expected to be more than 2 million by 2030.6 The prevalence of malnutrition progressively increases during the evolution of CKD. As a consequence, it has been reported that 40% of patients present with symptoms of undernutrition at the entrance to dialysis.7 In hemodialysis patients, the prevalence of protein-energy malnutrition, more correctly referred to as protein-energy wasting, varies from 20% to 60% according to which indicators of protein-energy wasting are used.8

Seminars in Nephrology, Vol 29, No 1, January 2009, pp 59-66

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Protein-energy wasting is associated with an increase in overall and cardiovascular death risks both in CKD patients not yet on dialysis9,10 and in chronic dialysis patients.11-13 Given the prognostic impact of protein-energy wasting in CKD patients, screening for wasting and malnutrition and monitoring protein-energy status appear to be of primary importance. Therefore, scientific and professional societies and foundations have developed guidelines for the assessment of nutritional status as well as for the treatment of protein-energy wasted CKD patients.14-19 Recently, an expert panel recommended the term protein-energy wasting for loss of body protein mass and fuel reserves. According to these recommendations, proteinenergy wasting should be diagnosed if 3 characteristics are present (low serum levels of albumin, transthyretin, or cholesterol), reduced body mass (low or reduced body mass or fat mass or weight loss with reduced intake of protein and energy), and reduced muscle mass (muscle wasting or sarcopenia, reduced mid– arm-muscle circumference).20 The present article addresses the methods for assessing proteinenergy status, their specificities regarding the CKD staging, and the criteria for choosing among these methods when managing CKD patients. The practical implications of nutritional parameters for the management of CKD patients is illustrated by a case presentation. METHODS FOR ASSESSMENT OF PROTEIN-ENERGY STATUS ASSESSMENT According to the National Kidney Foundation Clinical Practice Guidelines for Nutrition in Chronic Renal failure,14 nutritional status should be assessed with a combination of valid, complementary measures rather than any single measure alone. These measures include dietary intake assessment, anthropometry, serum proteins and cholesterol, urea and creatinine kinetics, subjective global assessment, and body composition measurements.

Dietary Records and Anthropometry The assessment of dietary intake is of primary importance in CKD patients. Dietary interviews

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and 3-day records (including 1 dialysis day and 1 weekend day) have been recommended for maintenance hemodialysis patients.14,15 They are the only way to quantify lipid and carbohydrate intakes. In stable conditions, protein intake also can be estimated by calculating the normalized protein nitrogen appearance (nPNA, see later). Besides its obvious usefulness in the hemodialysis setting, the follow-up evaluation of body weight is of great interest to detect protein-energy wasting. Body mass index (BMI), which was reported as an independent marker of survival, should be measured regularly.21,22 The relationships between BMI and survival even show a reverse epidemiology picture both in nondialyzed CKD patients and in dialysis patients.10,23 Anthropometric parameters can be influenced by water retention. In the absence of edema, triceps skinfold thickness (TSF) reflects fat stores and arm-muscle circumference (arm circumference ⫺ 3.14 ⫻ TSF), an indicator of muscle mass. TSF and arm-muscle circumference should be interpreted according to reference values specific for age and sex.24

Biological Assessment of Protein-Energy Status Serum albumin and transthyretin (prealbumin) remain major tools for evaluating protein-energy status, although their concentrations also are dependent on such non nutritional parameters as liver function, hydration, and inflammatory status.14 In hemodialysis patients, these proteins should be measured before a hemodialysis session. Serum albumin was shown to be correlated with multiple markers of protein-energy status such as nPNA, lean body mass, serum creatinine, transferrin, cholesterol, insulinlike growth factor-1 and transthyretin.8,11,25,26 The metabolism of serum transthyretin in CKD patients deserves some comments. As a matter of fact, CKD patients as compared with controls generally have higher serum transthyretin concentrations.27 Data suggest that the major cause of increased serum transthyretin in CKD is the decrease in the renal degradation of retinol-binding protein. The

Protein-energy status in CKD

subsequent increase of serum retinol-binding protein is responsible for an increase in the fraction of transthyretin linked to retinolbinding protein (normally close to 60%), and this is associated with a reduced degradation rate of transthyretin.27,28 As a consequence, serum transthyretin, which tends to increase together with the degree of reduction in renal function, should be considered only as a nutritional marker of wasting in conditions of stable renal function. In maintenance hemodialysis patients, renal function can be regarded as stable and insignificant, and serum transthyretin is recognized as a valid and clinically useful measure of protein-energy status.14 Indeed, serum transthyretin correlates with many other markers of protein-energy status including protein and energy intake, nPNA, body weight, BMI, arm-muscle circumference, TSF, lean body mass, serum creatinine, albumin, transferrin, and insulin-like growth factor-1.8,11,25,26 It has been recommended that the outcome goal for transthyretin is a value greater than 30 mg/dL in dialysis patients.14 Both serum albumin and transthyretin have been shown to be independent predictors of mortality in maintenance hemodialysis and chronic peritoneal dialysis patients.28,29 Moreover, in protein-energy wasted hemodialysis patients, transthyretin recently was shown to be of particular value for the monitoring of patients receiving nutritional support and more specifically for predicting the morbidity and mortality response to nutritional support30: an increase by 30 mg/L of serum transthyretin after 3 months was associated with a more than 2-fold increase in the 2-year survival. Although serum cholesterol is not usually considered to be a classic tool for monitoring protein-energy status in CKD patients, individuals with low or declining serum cholesterol levels should be investigated for possible nutritional risk factors that promote protein-energy wasting.14 The normalized protein equivalent of total nitrogen appearance (nPNA, g protein · kg⫺1 · dj⫺1) is calculated from the interdialytic changes in serum urea nitrogen and the urea nitrogen content in urine and dialysate. In clinically stable conditions, nPNA provides a valid estimate of protein intake and is correlated with lean body

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mass, serum albumin level, and serum transthyretin level.8 However, it must be emphasized that nPNA exceeds protein intake in catabolic patients. Predialysis serum creatinine and the creatinine index reflect the sum of endogenous creatinine production and dietary intakes of creatinine precursors. Low predialysis serum creatinine and creatinine index reflect low meat (protein) intake and/or decreased muscle mass, and indicate a need for an assessment of the protein-energy status. Both parameters have been shown to be correlated with outcome in chronic dialysis patients.11-13,31 Recently, in a clinical trial involving 187 patients, using multivariate analyses, serum transthyretin appeared to be the most predictive biological marker of noncardiovascular mortality (relative risk [RR], 3.78 [95% CI, 1.30-10.96]), and the creatinine index was most predictive of cardiovascular mortality (RR, 2.61 [95% CI, 1.06-6.46]). The investigators concluded that, in addition to serum transthyretin level, the creatinine index may be an additional useful marker of death risk that routinely is available in hemodialysis patients.32

Subjective Global Assessment The subjective global nutritional assessment (SGA) has been proposed as a simple, inexpensive, and easy-to-apply method using variables derived from history and physical examination.33 SGA now is considered to be a valid indicator of protein-energy wasting in uremic patients14,15 and was proposed as a component of the systematic monitoring of protein-energy wasting in chronic dialysis patients.14,17

Body Composition Bioelectrical impedance analysis (BIA), using a monofrequency procedure, makes it possible to assess fat mass and fat-free mass. Multifrequency BIA was reported to be a valid tool for measuring the ratio of extracellular water to total body water in subjects with end-stage renal disease.34 In hemodialysis patients, body cell mass estimated by BIA was shown to be highly correlated with body cell mass determined by dual-energy xray absorptiometry (DEXA) and deuterium oxide and sodium bromide isotope dilution studies.35 In hemodialysis patients, it was shown that BIA measurements fluctuate to a consider-

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Figure 1. Body composition assessment using monofrequency and multifrequency BIA together with DEXA.

able extent according to the point in time chosen for performing BIA, but remain constant and highly reproducible during the first 120 minutes after the end of hemodialysis, that is, in a dry-weight state.36 However, BIA results should be interpreted with caution in patients with body water changes. A standardization of the formulas used for calculation as well as a clear definition of the acceptable times to perform BIA, relative to the hemodialysis cycle, is needed to obtain reliable and reproducible results. DEXA does not enable one to distinguish between intracellular and extracellular water but remains the reference method for the precise measurements of body composition and bone mineral density.14 The concurrent measurements by DEXA and multifrequency BIA may be of interest for estimating body cell mass (Fig. 1). PROTEIN-ENERGY STATUS MONITORING IN CKD AND MAINTENANCE HEMODIALYSIS PATIENTS The rationale for the nutritional management of CKD patients with conservative treatment is to delay the need for dialysis by using low-protein diets, without compromising nutritional status.36 In this setting, both regular dietary counseling and protein-energy status assessment are of primary importance. A spontaneous decrease in oral food intake occurs together with the deterioration of

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renal function. Ikizler et al7 reported that the mean dietary protein intake was 1.01 ⫾ 0.21 g/kg/d, 0.85 ⫾ 0.23 g/kg/d, 0.70 ⫾ 0.17 g/kg/d, and 0.54 ⫾ 0.16 g/kg/d for patients with creatinine clearance greater than 50 mL/min, between 25 and 50 mL/min, between 10 and 25 mL/min, and less than 10 mL/min, respectively. In this study, it was calculated that each 10-mL/min decrease in creatinine clearance was associated with a 0.064- ⫾ 0.007-g/kg/d decrease in dietary protein intake.7 Protein intake, BMI, serum albumin level, transferrin level, and insulin-like growth factor-1 level decrease together with creatinine clearance.7,37,38 As a result, 40% of patients present with signs of protein-energy wasting at the onset of maintenance hemodialysis treatment.39 This point is of importance because malnutrition at the time that patients commence dialysis therapy is a strong predictor of poor survival rate.40-42 Goldwasser et al41 observed that survival after 12 and 24 months of maintenance hemodialysis therapy was 88% and 76% when the serum albumin level was 3.5 g/dL or greater at the initiation of hemodialysis, and 50% and 16% when the serum albumin level was less than 3.5 g/dL, respectively.41 To prevent the deterioration of nutritional status during the progression of CKD, high-energy intakes are recommended together with a close follow-up evaluation by the dietician and nephrologist.43 According to the Kidney Disease Outcomes Quality Initiative (K/DOQI) Recommendations for Nutritional Management guidelines, dietary interviews and counseling should be performed every 3 to 4 months, and serum albumin level, together with body weight and SGA, should be monitored every 1 to 3 months.14 Protein-energy wasting is a strong predictor of death among maintenance dialysis patients, in those undergoing either chronic hemodialysis or peritoneal dialysis. A key purpose for monitoring of protein-energy status is to adjust nutritional intakes to the patient’s nutritional needs thanks to dietician intervention, to detect markers of undernutrition, and to identify patients requiring nutritional support in the form of oral nutritional supplements (ONS), intradialytic parenteral nutrition (IDPN), or enteral nutrition. Table 1 gives recommended nutritional parameters for patients undergoing maintenance dialysis, according to the K/DOQ and European Best Practice Guidelines on nutrition. Main measures for

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Table 1. Parameters for Nutritional Assessment of Patients Undergoing Maintenance Dialysis, as Recommended by the National Kidney Foundation and European Dialysis Transplantation Association

NKF K/DOQI (hemodialysis and peritoneal dialysis)

European Best Practice Guidelines on nutrition (hemodialysis)

Measurements that should be measured routinely in all patients, frequency of measurement, and recommended levels (when given in the guideline): Dietary interviews, every 6-12 months or every 3 months in patients older than 50 years of age or on hemodialysis for more than 5 years Body weight and BMI, average postdialysis body weight over the month and percentage change in the average body weight; BMI should be ⬎23.0 nPNA, 1 month after beginning hemodialysis and every 3 months thereafter; normalized PNA should be ⬎1.0 g/kg ideal body weight/d Serum albumin, 1 month after beginning hemodialysis and every 3 months thereafter; serum albumin level should be ⬎40 g/L by bromocresol green method Serum transthyretin level should be ⬎300 mg/L Serum cholesterol level should be ⬎minimal laboratory threshold value Useful measures to confirm or extend data: Useful measures to confirm or extend category one data: Predialysis or stabilized serum transthyretin (should SGA should be used to identify severe be ⱖ300 mg/L) malnutrition in hemodialysis patients Skinfold thickness Anthropometry should be assessed Mid–arm-muscle area circumference or diameter immediately after dialysis, midarm Whole-body DEXA circumference, mid–arm-muscle circumference, and 4-site skinfold thickness should be performed by the same individual on the nonfistula arm Other measures: Measurements for research purposes: Measures that, if low, suggest the need for further Technical tools such as BIA, DEXA, nearnutritional assessment: infrared interactance, and in vivo neutron Predialysis or stabilized creatinine level activation analysis Urea nitrogen level Cholesterol level Creatinine index Predialysis or stabilized serum albumin, monthly; serum albumin level should be ⱖ40 g/L by bromocresol green method Percentage of usual postdialysis (hemodialysis) or postdrain (peritoneal dialysis), monthly Percentage of standard (NHANES II) body weight, every 4 months SGA, every 6 months Dietary interview and/or diary nPNA, every 6 months

Data from the National Kidney Foundation,14 and Fouque et al.17

the routine assessment of protein-energy status are body weight variations, BMI, nPNA, serum albumin level, and transthyretin level. These parameters are dependent not only on protein-energy status, but also on such other factors as hydration status, inflam-

mation, and protein catabolism. Therefore, one should take into account these other possible causes when establishing the diagnosis of protein-energy wasting, assessing the possible causes and developing a treatment strategy for these conditions.

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PRACTICAL IMPLICATIONS OF NUTRITIONAL PARAMETERS FOR THE MANAGEMENT OF CKD AND MAINTENANCE DIALYSIS PATIENTS

Case Presentation

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nance dialysis or renal transplantation should be performed in advanced CKD patients with frank protein-energy wasting when there is no other apparent cause of this wasting and efforts to correct the protein-energy wasting are unsuccessful.14 On May 7, 2007, maintenance hemodialysis was initiated. On July 10, 2007, a slight improvement in appetite was observed. Body weight and BMI were unchanged. Triceps skinfold was 6 mm, and arm-muscle circumference was 245 mm (both close to the fifth percentile of reference values24), serum albumin level was 3.4 g/dL, serum transthyretin level was 250 mg/dL, serum C-reactive protein level was 10 mg/L, serum bicarbonate level was 23 mmol/L, and hemoglobin level was 11.8 g/100 mL. A dietary interview indicated that the protein intake was 1.0 g/kg/d and energy intake was 25 kcal/kg/d.

Our patient was a 45-year-old man with chronic glomerulonephritis and chronic renal failure. On January 7, 2007, an outpatient consultation was performed. The patient interview revealed a poor appetite and mild nausea. At examination no evidence of associated comorbidity was found. Body weight was 55 kg, body weight loss was 6 kg within 18 months, height was 170 cm, and BMI was 19. The glomerular filtration rate was 15 mL/min without any change within the previous 3 months, urine output was 1,700 mL/d, serum albumin level was 3.4 g/dL, serum C-reactive protein level was 10 mg/L, serum potassium level was 4.5 mEq/L, serum bicarbonate level was 24 mmol/L, and blood hemoglobin level was 11.5 g/100 mL. A dietary interview indicated that the daily energy intake was 1,500 kcal/d and protein intake was 45 g/dL. The physician decided to obtain gastroenterologic advice, and nutritional counseling by a dietician to provide an oral energy and protein supplement (500 kcal and 30 g protein/d). On April 10, 2007, at the outpatient follow-up evaluation, the persistence of asthenia and anorexia was noticed. Clinical examination was unchanged. Body weight was 55 kg, glomerular filtration rate was 14 mL/min, serum albumin level was 3.3 g/dL, serum C-reactive protein level was 9 mg/L, serum potassium level was 4.6 mEq/L, serum bicarbonate level was 23 mmol/L, and hemoglobin level was 11.5 g/100 mL. No gastroenterologic explanation for the anorexia and nausea was found. The physician decided to initiate maintenance dialysis.

The association of low serum albumin and transthyretin levels together with reduced body mass (as attested by low BMI and triceps skinfold) and reduced muscle mass (low arm-muscle circumference) confirms the diagnosis of overt protein-energy wasting.20 According to a recent interventional study, the association of 2 of the following nutritional abnormalities can be used for detecting severe malnutrition, indicating the need for nutritional support: body weight loss greater than 10% within 6 months, BMI less than 20 kg/m2, serum albumin level less than 3.5 g/dL, and transthyretin level less than 300 mg/dL.30

Question 1

Question 3

Is the initiation of hemodialysis justified?

Which type of nutritional support should be used: dietician counseling, ONS, IDPN, or enteral nutrition?

Comment 1 This case report underlines the effect of nutritional follow-up evaluation on CKD patient management. According to K/DOQUI guidelines, because of the association between protein-energy wasting and poor outcome, mainte-

Question 2 Is nutritional support indicated?

Comment 2

Comment 3 Nutritional counseling by a dietician was shown to be helpful and should occur early on during these conditions, thereafter every 1 or 2

Protein-energy status in CKD

months.14,44 ONS have been shown to be able to improve nutritional status in malnourished hemodialysis patients. Moreover, it recently was shown that during oral supplementation, an increase in serum transthyretin level by 30 mg/L after 3 months was associated with a 2-fold increase in the 2-year survival.30 In the same study, no further beneficial effect was observed when IDPN was added to ONS. As a consequence, IDPN should be proposed only in patients who are not compliant or not tolerating ONS. In the present case, with a daily energy intake of 25 kcal/kg/d, ONS should make it possible to reach the recommended levels of energy and protein intakes (30-35 kcal/kg/d and 1.2 g protein/kg/d, respectively).14,17 Daily enteral nutrition by tube feeding or gastrostomy should be considered in the absence of improvement under ONS treatment.45 On October 6, 2007, at an examination during a hemodialysis session, the patient showed a normal appetite and no noticeable asthenia. Body weight was 58 kg and BMI was 20. Triceps skinfold was 9 mm, and arm-muscle circumference was 255 mm, serum albumin level was 3.7 gd/L, serum transthyretin level was 290 mg/dL. It was decided to continue ONS until the BMI, serum albumin level, and transthyretin level reached the recommended levels (Table 1). CONCLUSIONS The initial assessment and routine monitoring of protein-energy status during the course of CKD is of the first importance. Such an assessment mainly refers to simple and routine measurements such as body weight, BMI, nPNA, serum albumin, and transthyretin. In nondialyzed CKD patients given low-protein diets, nutritional status must be monitored to detect the occurrence of protein-energy wasting. In this setting, protein-energy wasting requires intensive nutritional counseling and nutritional supplementation. In patients with severe renal failure, the persistence of protein-energy wasting, despite these treatments, should lead one to consider the initiation of maintenance dialysis therapy or renal transplantation. In maintenance dialysis patients, protein-energy wasting is a major risk factor for survival. The decline of nutritional markers, and particularly of serum

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albumin and transthyretin levels, indicates a need for implementing nutritional support. The improvement of nutritional status in patients receiving oral supplements, and, more precisely, the increase in serum transthyretin level is associated with an improved survival. REFERENCES 1. Vassalotti JA, Stevens LA, Levey AS. Testing for chronic kidney disease: a position statement from the National Kidney Foundation. Am J Kidney Dis. 2007;50:169-80. 2. Hallan SI, Coresh J, Astor BC, Asberg A, Powe NR, Romundstad S, et al. International comparison of the relationship of chronic kidney disease prevalence and ESRD risk. J Am Soc Nephrol. 2006;17:2275-84. 3. Chadban SJ, Briganti EM, Kerr PG, Dunstan DW, Welborn TA, Zimmet PZ, et al. Prevalence of kidney damage in Australian adults: the AusDiab kidney study. J Am Soc Nephrol. 2003;14 Suppl 2:S131-8. 4. Zhang L, Zhang P, Wang F, Zuo L, Zhou Y, Shi Y, et al. Prevalence and factors associated with CKD: a population study from Beijing. Am J Kidney Dis. 2008;51:373-84. 5. Cusumano AM, Gonzalez Bedat MC. Chronic kidney disease in Latin America: time to improve screening and detection. Clin J Am Soc Nephrol. 2008;3:594-600. 6. Gilbertson DT, Liu J, Xue JL, Louis TA, Solid CA, Ebben JP, et al. Projecting the number of patients with end-stage renal disease in the United States to the year 2015. J Am Soc Nephrol. 2005;16:3736-41. 7. Ikizler TA, Greene JH, Wingard RL, Parker RA, Hakim RM. Spontaneous dietary protein intake during progression of chronic renal failure. J Am Soc Nephrol. 1995;6:1386-91. 8. Aparicio M, Cano N, Chauveau P, Azar R, Canaud B, Flory A, et al. Nutritional status of haemodialysis patients: a French national cooperative study. French Study Group for Nutrition in Dialysis. Nephrol Dial Transplant. 1999;14:1679-86. 9. Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L, et al. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int. 1999;55:1899-911. 10. Kovesdy CP, Anderson JE, Kalantar-Zadeh K. Paradoxical association between body mass index and mortality in men with CKD not yet on dialysis. Am J Kidney Dis. 2007;49:581-91. 11. Cano N, Fernandez JP, Lacombe P, Lankester M, Pascal S, Defayolle M, et al. Statistical selection of nutritional parameters in hemodialyzed patients. Kidney Int. 1987;32 Suppl 22:S178-80. 12. Combe C, Chauveau P, Laville M, Fouque D, Azar R, Cano N, et al. Influence of nutritional factors and hemodialysis adequacy on the survival of 1,610 French patients. Am J Kidney Dis. 2001;37 Suppl 2:S81-8. 13. Owen WF Jr, Lew NL, Liu Y, Lowrie EG, Lazarus JM. The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis. N Engl J Med. 1993;329:1001-6.

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14. K/DOQI, National Kidney Foundation. Clinical practice guidelines for nutrition in chronic renal failure. Am J Kidney Dis. 2000;35 Suppl 2:S1-140. 15. Toigo G, Aparicio M, Attman PO, Cano N, Cianciaruso B, Engel B, et al. Expert Working Group report on nutrition in adult patients with renal insufficiency (part 1 of 2). Clin Nutr. 2000;19:197-207. 16. Toigo G, Aparicio M, Attman PO, Cano N, Cianciaruso B, Engel B, et al. Expert working group report on nutrition in adult patients with renal insufficiency (part 2 of 2). Clin Nutr. 2000;19:281-91. 17. Fouque D, Vennegoor M, ter Wee P, Wanner C, Basci A, Canaud B, et al. EBPG guideline on nutrition. Nephrol Dial Transplant. 2007;22 Suppl 2:ii45-87. 18. Cano N, Fiaccadori E, Tesinsky P, Toigo G, Druml W, Kuhlmann M, et al. ESPEN guidelines on enteral nutrition: adult renal failure. Clin Nutr. 2006;25:295310. 19. Cano NJM, Aparicio M, Brunori G, Carrero JJ, Cianciaruso B, Fiaccadori E, et al. ESPEN guidelines on parenteral nutrition: adult renal failure. Clin Nutr. 2008. In press. 20. Fouque 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;73:391-8. 21. Kopple JD, Zhu X, Lew NL, Lowrie EG. Body weightfor-height relationships predict mortality in maintenance hemodialysis patients. Kidney Int. 1999;56:113648. 22. Leavey SF, Strawderman RL, Jones CA, Port FK, Held PJ. Simple nutritional indicators as independent predictors of mortality in hemodialysis patients. Am J Kidney Dis. 1998;31:997-1006. 23. Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int. 2003;63:793-808. 24. Frisancho AR. New norms of upper limb fat and muscle areas for assessment of nutritional status. Am J Clin Nutr. 1981;34:2540-5. 25. Jacob V, LeCarpentier JE, Salzano S, Naylor V, Wild G, Brown CB, et al. IGF-1, a marker of undernutrition in hemodialysis patients. Am J Clin Nutr. 1990;52:39-44. 26. Goldwasser P, Michel MA, Collier J, Mittman N, Fein PA, Gusik SA, et al. Prealbumin and lipoprotein(a) in hemodialysis: relationships with patient and vascular access survival. Am J Kidney Dis. 1993;21:215-25. 27. Cano N, Di Costanzo-Dufetel J, Calaf R, Durbec JP, Lacombe P, Pascal S. Prealbumin-retinol-binding-protein-retinol complex in hemodialysis patients. Am J Clin Nutr. 1988;47:664-7. 28. Cano NJ. Metabolism and clinical interest of serum transthyretin (prealbumin) in dialysis patients. Clin Chem Lab Med. 2002;40:1313-9. 29. Chertow GM, Ackert K, Lew NL, Lazarus JM, Lowrie EG. Prealbumin is as important as albumin in the nutritional assessment of hemodialysis patients. Kidney Int. 2000;58:2512-7.

N.J.M. Cano et al

30. Cano NJ, Fouque D, Roth H, Aparicio M, Azar R, Canaud B, et al. Intradialytic parenteral nutrition does not improve survival in malnourished hemodialysis patients: a 2-year multicenter, prospective, randomized study. J Am Soc Nephrol. 2007;18:2583-91. 31. Canaud B, Garred LJ, Argiles A, Flavier JL, Bouloux C, Mion C. Creatinine kinetic modelling: a simple and reliable tool for the assessment of protein nutritional status in haemodialysis patients. Nephrol Dial Transplant. 1995;10:1405-10. 32. Terrier N, Jaussent I, Dupuy AM, Morena M, Delcourt C, Chalabi L, et al. Creatinine index and transthyretin as additive predictors of mortality in haemodialysis patients. Nephrol Dial Transplant. 2008;23:345-53. 33. Detsky AS, McLaughin JR, Baker JP. What is subjective global assessment of nutritional status? JPEN J Parenter Enteral Nutr. 1987;11:8-13. 34. Cha K, Chertow GM, Gonzalez J, Lazarus JM, Wilmore DW. Multifrequency bioelectrical impedance estimates the distribution of body water. J Appl Physiol. 1995;79:1316-9. 35. Chertow GM, Lowrie EG, Wilmore DW, Gonzalez J, Lew NL, Ling J, et al. Nutritional assessment with bioelectrical impedance analysis in maintenance hemodialysis patients. J Am Soc Nephrol. 1995;6:75-81. 36. Fouque D, Aparicio M. Eleven reasons to control the protein intake of patients with chronic kidney disease. Nat Clin Pract Nephrol. 2007;3:383-92. 37. Pollock CA, Ibels LS, Zhu FY, Warnant M, Caterson RJ, Waugh DA, et al. Protein intake in renal disease. J Am Soc Nephrol. 1997;8:777-83. 38. Kopple JD, Berg R, Houser H, Steinman TI, Teschan P. Nutritional status of patients with different levels of chronic renal insufficiency. Kidney Int. 1989;36 Suppl 27:S184-94. 39. Ikizler TA, Hakim RM. Nutrition in end-stage renal disease. Kidney Int. 1996;50:343-57. 40. Kopple JD, Blumenkrantz MJ, Jones MR, Moran JK, Coburn JW. Plasma amino acid levels and amino acid losses during continuous ambulatory peritoneal dialysis. Am J Clin Nutr. 1982;36:395-402. 41. Goldwasser P, Mittman N, Antignani A, Burrell D, Michel MA, Collier J, et al. Predictors of mortality in hemodialysis patients. J Am Soc Nephrol. 1993;3:161322. 42. Avram MM, Goldwasser P, Erroa M, Fein PA. Predictors of survival in continuous ambulatory peritoneal dialysis patients: the importance of prealbumin and other nutritional and metabolic markers. Am J Kidney Dis. 1994;23:91-8. 43. Aparicio M, Chauveau P, Combe C. Low protein diets and outcome of renal patients. J Nephrol. 2001;14:433-9. 44. Leon JB, Majerle AD, Soinski JA, Kushner I, OhriVachaspati P, Sehgal AR. Can a nutrition intervention improve albumin levels among hemodialysis patients? A pilot study. J Ren Nutr. 2001;11:9-15. 45. Cano N. Nutritional supplementation in adult patients on hemodialysis. J Ren Nutr. 2007;17:103-5.