Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism.

Protein energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes, especially in individuals receiving maintenance dialysis therapy. A multitude of factors can affect the nutritional and metabolic status of CKD patients requiring a combination of therapeutic maneuvers to prevent or reverse protein and energy depletion. These include optimizing dietary nutrient intake, appropriate treatment of metabolic disturbances such as metabolic acidosis, systemic inflammation, and hormonal deficiencies, and prescribing optimized dialytic regimens. In patients where oral dietary intake from regular meals cannot maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is shown to be effective in replenishing protein and energy stores. In clinical practice, the advantages of oral nutritional supplements include proven efficacy, safety, and compliance. Anabolic strategies such as anabolic steroids, growth hormone, and exercise, in combination with nutritional supplementation or alone, have been shown to improve protein stores and represent potential additional approaches for the treatment of PEW. Appetite stimulants, anti-inflammatory interventions, and newer anabolic agents are emerging as novel therapies. While numerous epidemiological data suggest that an improvement in biomarkers of nutritional status is associated with improved survival, there are no large randomized clinical trials that have tested the effectiveness of nutritional interventions on mortality and morbidity.

Multimodal nutritional rehabilitation improves clinical outcomes of malnourished patients with chronic respiratory failure: a randomised controlled trial.

BACKGROUND: In chronic respiratory failure (CRF), body composition strongly predicts survival. METHODS: A prospective randomised controlled trial was undertaken in malnourished patients with CRF to evaluate the effects of 3 months of home rehabilitation on body functioning and composition. 122 patients with CRF on long-term oxygen therapy and/or non-invasive ventilation (mean (SD) age 66 (10) years, 91 men) were included from eight respiratory units; 62 were assigned to home health education (controls) and 60 to multimodal nutritional rehabilitation combining health education, oral nutritional supplements, exercise and oral testosterone for 90 days. The primary endpoint was exercise tolerance assessed by the 6-min walking test (6MWT). Secondary endpoints were body composition, quality of life after 3 months and 15-month survival. RESULTS: Mean (SD) baseline arterial oxygen tension was 7.7 (1.2) kPa, forced expiratory volume in 1 s 31 (13)% predicted, body mass index (BMI) 21.5 (3.9) kg/m2 and fat-free mass index (FFMI) 15.5 (2.4) kg/m2. The intervention had no significant effect on 6MWT. Improvements (treatment effect) were seen in BMI (+0.56 kg/m2, 95% CI 0.18 to 0.95, p=0.004), FFMI (+0.60 kg/m2, 95% CI 0.15 to 1.05, p=0.01), haemoglobin (+9.1 g/l, 95% CI 2.5 to 15.7, p=0.008), peak workload (+7.2 W, 95% CI 3.7 to 10.6, p<0.001), quadriceps isometric force (+28.3 N, 95% CI 7.2 to 49.3, p=0.009), endurance time (+5.9 min, 95% CI 3.1 to 8.8, p<0.001) and, in women, Chronic Respiratory Questionnaire (+16.5 units, 95% CI 5.3 to 27.7, p=0.006). In a multivariate Cox analysis, only rehabilitation in a per-protocol analysis predicted survival (HR 0.27, 95% CI 0.07 to 0.95, p=0.042). CONCLUSIONS: Multimodal nutritional rehabilitation aimed at improving body composition increased exercise tolerance, quality of life in women and survival in compliant patients, supporting its incorporation in the treatment of malnourished patients with CRF. Clinical Trial number NCT00230984.

Multimodal approach to malnutrition in malnourished maintenance hemodialysis patients.

Chronic organ failures, including chronic kidney disease, cardiac failure, and chronic pulmonary disease, share a common phenotype which is characterized by a high prevalence of anorexia, inflammation, oxidative stress, insulin resistance, hypogonadism, and anemia. Because of the systemic dimension of organ failure, such a phenotype results in a decrease in body mass, in addition to alterations of body composition and abnormal muscle structure, metabolism, and performance. The response of both protein-energy wasting and muscle disease to nutritional support given alone was shown to be limited both in chronic kidney disease and chronic pulmonary disease. Data are needed to evaluate the effects of an integrated management taking into account the different factor of muscle anabolism: nutrition support, endurance exercise, and, in selected patients, other anabolic agents such as androgens and omega-3 fatty acids.

Assessment of body protein: energy status in chronic kidney disease.

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.

Survival of patients with chronic respiratory failure on long-term oxygen therapy and or non-invasive ventilation at home.

BACKGROUND & AIMS: Chronic respiratory failure (CRF) is the common fate of respiratory diseases where systemic effects contribute to outcomes. In a prospective cohort of home-treated patients with CRF, we looked for predictors of long-term survival including respiratory, nutritional and inflammatory dimensions. METHODS: 637 stable outpatients with CRF, 397 men, 68 ± 11 years, on long-term oxygen therapy and/or non-invasive ventilation from 21 chest clinics were enrolled and followed over 53 ± 31 months. CRF resulted from Chronic Obstructive Pulmonary Disease (COPD) in 48.5%, restrictive disorders 32%, mixed (obstructive and restrictive patterns) respiratory failure 13.5%, bronchiectasis 6%. Demographic characteristics, smoking habits, underlying respiratory diseases, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), arterial blood gases, 6-min walking distance (6MWD), hemoglobin, body mass index (BMI), serum albumin, transthyretin, C-reactive protein (CRP), history of respiratory assistance, antibiotic and oral corticosteroid use during the previous year were recorded. RESULTS: 322 deaths occurred during the follow-up. One-, five- and 8-year actuarial survival was 89%, 56% and 47%. By Cox univariate analysis, age, respiratory disease, PaO2, PaCO2, FEV1/FVC, BMI, 6MWD, activity score, type and length of home respiratory assistance, smoking habits, oral corticosteroid and antibiotic uses, albumin, transthyretin, hemoglobin and CRP levels were associated with survival. Multivariate analysis identified eight independent markers of survival: age, FEV1/FVC, PaO2, PaCO2, 6MWD, BMI, serum transthyretin, CRP ≥ 5 mg/l. CONCLUSIONS: In CRF, whatever the underlying diseases, besides the levels of obstructive ventilatory defect and gas exchange failure, 6MWD, BMI, serum transthyretin and CRP ≥ 5 mg/l predicted long-term survival identifying potential targets for nutritional rehabilitation.

C-reactive protein and body mass index predict outcome in end-stage respiratory failure.

STUDY OBJECTIVE: To determine the predictive factors of morbidity and mortality in patients with end-stage respiratory disease. DESIGN: Prospective, multicenter cohort study. SETTING: Thirteen outpatient chest clinics within the Association Nationale de Traitement à Domicile de l'Insuffisance Respiratoire. PARTICIPANTS: Stable adult patients with chronic respiratory failure receiving long-term oxygen therapy and/or home mechanical ventilation (n = 446; 182 women and 264 men; aged 68.5 +/- 12.1 years [+/- SD]); Respiratory diseases were COPD in 42.8%, restrictive disorders in 36.3%, mixed respiratory failure in 13.5%, and bronchiectasis in 7.4%. Recruitment was performed during the yearly examination. Patients with neuromuscular diseases and sleeping apnea were excluded. MEASUREMENTS AND RESULTS: Hospitalization days and survival were recorded during a follow-up of 14.3 +/- 5.6 months. Body mass index (BMI), serum albumin, and transthyretin levels were considered for their predictive value of outcome, together with demographic data, underlying respiratory disease, respiratory function, hemoglobin, C-reactive protein, smoking habits, oral corticosteroid use, and antibiotic treatment courses. Overall, 1.8 +/- 1.7 hospitalizations (cumulative stay, 17.6 +/- 27.1 days) were observed in 254 of 446 patients (57%). Independent predictors of hospitalization were oral corticosteroids, FEV(1), and plasma C-reactive protein. One-year and 2-year cumulative survivals were 93% and 69%, respectively. Plasma C-reactive protein, BMI, Pao(2) on room air, and oral corticosteroids independently predicted survival in multivariate analysis. CONCLUSION: Besides established prognosis factors such as FEV(1) and Pao(2), nutritional depletion as assessed by BMI and overall systemic inflammation as estimated by C-reactive protein appear as major determinants of hospitalization and death risks whatever the end-stage respiratory disease. BMI and C-reactive protein should be included in the monitoring of chronic respiratory failure. Oral corticosteroids as maintenance treatment in patients with end-stage respiratory disease are an independent risk factor of death, and should be avoided in most cases.

Nutrition and protein energy homeostasis in elderly.

Protein-energy homeostasis is a major determinant of healthy aging. Inadequate nutritional intakes and physical activity, together with endocrine disturbances are associated with of sarcopenia and frailty. Guidelines from scientific societies mainly address the quantitative aspects of protein and energy nutrition in elderly. Besides these quantitative aspects of protein load, perspective strategies to promote muscle protein synthesis and prevent sarcopenia include pulse feeding, the use of fast proteins and the addition of leucine or citrulline to dietary protein. An integrated management of sarcopenia, taking into account the determinants of muscle wasting, i.e. nutrition, physical activity, anabolic factors such as androgens, vitamin D and n-3 polyunsaturated fatty acids status, needs to be tested in the prevention and treatment of sarcopenia. The importance of physical activity, specifically resistance training, is emphasized, not only in order to facilitate muscle protein anabolism but also to increase appetite and food intake in elderly people at risk of malnutrition. According to present data, healthy nutrition in elderly should respect the guidelines for protein and energy requirement, privilege a Mediterranean way of alimentation, and be associated with a regular physical activity. Further issues relate to the identification of the genetics determinants of protein energy wasting in elderly.

Diets and enteral supplements for improving outcomes in chronic kidney disease.

Protein-energy wasting (PEW), which is manifested by low serum levels of albumin or prealbumin, sarcopenia and weight loss, is one of the strongest predictors of mortality in patients with chronic kidney disease (CKD). Although PEW might be engendered by non-nutritional conditions, such as inflammation or other comorbidities, the question of causality does not refute the effectiveness of dietary interventions and nutritional support in improving outcomes in patients with CKD. The literature indicates that PEW can be mitigated or corrected with an appropriate diet and enteral nutritional support that targets dietary protein intake. In-center meals or oral supplements provided during dialysis therapy are feasible and inexpensive interventions that might improve survival and quality of life in patients with CKD. Dietary requirements and enteral nutritional support must also be considered in patients with CKD and diabetes mellitus, in patients undergoing peritoneal dialysis, renal transplant recipients, and in children with CKD. Adjunctive pharmacological therapies, such as appetite stimulants, anabolic hormones, and antioxidative or anti-inflammatory agents, might augment dietary interventions. Intraperitoneal or intradialytic parenteral nutrition should be considered for patients with PEW whenever enteral interventions are not possible or are ineffective. Controlled trials are needed to better assess the effectiveness of in-center meals and oral supplements.

Intradialytic nutritional support.

PURPOSE OF REVIEW: Intradialytic nutritional support has been used for more than 30 years both in critically ill patients with acute renal failure and during maintenance hemodialysis. Present knowledge allows better estimation of its metabolic and nutritional efficacy, as well its effect on patient outcome. RECENT FINDINGS: Recent data showed that intradialytic nutritional support is able to counteract these effects of dialysis on protein metabolism and to improve both nitrogen and energy balance. In maintenance hemodialysis patients, the improvement of nutritional status during nutritional support was shown to improve long-term survival. In critically ill patients with acute renal failure, protein sparing is one of the main therapeutic goals. The effect of nutritional support on patient outcome is not demonstrated. Recent data, however, showed that the improvement of nitrogen balance may be associated with a better outcome. SUMMARY: Current information helps to better assess the effects of intradialytic nutritional support, to clarify the nutritional management of renal failure patients and to provide recommendations. Future research should focus on the possible means to improve the efficacy of nutritional support, either by modifying its components of by associating anabolic or anticatabolic agents.

Nutritional management in acute illness and acute kidney insufficiency.

There are now powerful compensatory therapies to counteract kidney deficiency and the prognosis of patients with acute renal failure is mainly related to the severity of the initial disease. Renal failure is accompanied by an increase in both severity and duration of the catabolic phase leading to stronger catabolic consequences. The specificity of the metabolic and nutritional disorders in the most severely ill patients is the consequence of three additive phenomena: (1) the metabolic response to stress and to organ dysfunction, (2) the lack of normal kidney function and (3) the interference with the renal treatment (hemodialysis, hemofiltration or both, continuous or intermittent, lactate or bicarbonate buffer, etc.). As in many other diseases of similar severity, adequate nutritional support in acutely ill patients with ARF is of great interest in clinical practice, although the real improvement as a result of this support is still difficult to assess in terms of morbidity or mortality.

Intradialytic parenteral nutrition does not improve survival in malnourished hemodialysis patients: a 2-year multicenter, prospective, randomized study.

Although intradialytic parenteral nutrition (IDPN) is a method used widely to combat protein-calorie malnutrition in hemodialysis patients, its effect on survival has not been thoroughly studied. We conducted a prospective, randomized trial in which 186 malnourished hemodialysis patients received oral nutritional supplements with or without 1 year of IDPN. IDPN did not improve 2-year mortality (primary end point), hospitalization rate, Karnofsky score, body mass index, or laboratory markers of nutritional status. Instead, both groups demonstrated improvement in body mass index and the nutritional parameters serum albumin and prealbumin (P < 0.05). Multivariate analysis showed that an increase in prealbumin of >30 mg/L within 3 months, a marker of nutritional improvement, independently predicted a 54% decrease in 2-year mortality, as well as reduced hospitalizations and improved general well-being as measured by the Karnofsky score. Therefore, although we found no definite advantage of adding IDPN to oral nutritional supplementation, this is the first prospective study demonstrating that an improvement in prealbumin during nutritional therapy is associated with a decrease in morbidity and mortality in malnourished hemodialysis patients.

Application of branched-chain amino acids in human pathological states: renal failure.

During renal failure, abnormalities of BCAA and branched-chain keto acid (BCKA) metabolism are due to both the lack of renal contribution to amino acid metabolism and the impact of renal failure and acidosis on whole-body nitrogen metabolism. Abnormal BCAA and BCKA metabolism result in BCAA depletion as reflected by low plasma BCAAs and cellular valine. BCAA metabolic disturbances can alter tissue activities, particularly brain function, and nutritional status. In dialysis patients, BCAA oral supplementation can induce an improvement of appetite and nutritional status. During chronic renal failure, the aims of nutritional interventions are to minimize uremic toxicity, avoid malnutrition and delay progression of kidney disease. BCAA and BCKA supplements have been proposed to decrease further protein intake while maintaining satisfactory nutritional status. In this setting, BCAAs or BCKAs have not been administrated solely but in association with other essential AA or keto analogs. Therefore, the proper effects of BCAAs and/or BCKAs have not been studied separately. Protein restriction together with keto acids and/or essential AAs has been reported to improve insulin sensitivity and hyperparathyroidism and to be compatible with a preservation of nutritional status. Nonetheless, a careful monitoring of protein-calorie intake and nutritional status is needed. A recent meta-analysis concluded that reducing protein intake in patients with chronic renal failure reduces the occurrence of renal death by approximately 40% as compared with larger or unrestricted protein intake. The additional effect of essential amino acids and keto acids on retardation of progression of renal failure has not been demonstrated.

Intradialytic parenteral nutrition: comparison of olive oil versus soybean oil-based lipid emulsions.

Lipid, oxidative and inflammatory parameters are frequently altered in dialysis patients and may be worsened by intravenous lipid emulsions (ILE). We assessed the efficacy and tolerance of olive as compared with standard soybean oil-based ILE during intradialytic parenteral nutrition (IDPN). IDPN mixtures containing amino acids, glucose, and either olive oil (OO group, n 17) or soybean oil-based ILE (SO group, n 18) were administered in a 5-week randomized, double-blind study. On days 0 and 35, patients' nutritional status was assessed by BMI, normalized protein catabolic rate, predialytic creatinine, serum albumin and transthyretin; lipid metabolism by plasma LDL- and HDL-cholesterol, triacylglycerols, phospholipids, apo A-I, A-II, B, C-II, C-III, E and lipoprotein (a); oxidative status by alpha-tocopherol, retinol, selenium, glutathione peroxidase, malondialdehyde and advanced oxidized protein products; inflammatory status by serum C-reactive protein, orosomucoid, IL-2 and IL-6. No serious adverse event was observed. Significant changes were observed from day 0 to day 35 (P<0.05): nutritional criteria improved (albumin in OO; albumin, transthyretin and creatinine in SO); LDL-cholesterol, apo B, C-II, C-III and apo A-I/A-II ratio increased in both groups. HDL-cholesterol decreased in OO; apo E increased and lipoprotein (a) decreased in SO; alpha-tocopherol/cholesterol ratio increased in OO; malondialdehyde decreased in both groups; IL-2 increased in both groups. The between-group comparison only showed the following differences: alpha-tocopherol/cholesterol increased in OO; lipoprotein (a) decreased in SO. From these data, it was concluded that OO- and SO-based IDPNs similarly improved nutritional status and influenced plasma lipid, oxidative, inflammatory and immune parameters.

Metabolism and clinical interest of serum transthyretin (prealbumin) in dialysis patients.

Chronic renal failure is responsible for an increase in serum concentrations of transthyretin. Elevated serum transthyretin during renal insufficiency is secondary to the lack of retinol-binding protein degradation in renal tubules and to the subsequent increase in the fraction of transthyretin bound to retinol-binding protein. In both hemodialysis and peritoneal dialysis patients, serum transthyretin was demonstrated to be a reliable marker of nutritional status, exhibiting significant relationships with energy and protein intakes as well as with fat stores and lean body mass. Serum transthyretin levels less than 300 mg/l were shown to be associated with an increased risk of morbidity and mortality in dialysis patients. The predictive value of transthyretin was shown to be independent of serum albumin. Regular measurements of both serum albumin and transthyretin make it possible to detect patients whose prognosis is compromised by malnutrition and in whom an active nutritional therapy must be undertaken. Simultaneous measurements of inflammatory markers such as serum C-reactive protein are required to evaluate the role of inflammation in serum albumin and transthyretin variations. These low-cost protein parameters should be incorporated in the regular assessment of dialysis patients and measured every 1 to 3 months.

Malnutrition in hemodialysis diabetic patients: evaluation and prognostic influence.

BACKGROUND: This work aimed to evaluate the role of malnutrition in the increased mortality rate of hemodialysis diabetic patients from a French cooperative series. METHODS: Body mass index (BMI), serum albumin, prealbumin, cholesterol, and pre-dialysis creatinine, normalized protein catabolic rate and lean body mass (LBM) were measured in 734 diabetic and 6389 non-diabetic patients (aged 63.4 +/- 12.2 and 62.0 +/- 15.9 years; 1.01 male to 1.40 female ratio). The outcome of 1610 of these patients, including 170 diabetics, was assessed during a 30-month follow-up. RESULTS: Diabetic as compared to non-diabetic patients showed a significant (P < 10-4) increased BMI (25.9 +/- 5.2 vs. 23.1 +/- 4.3) and cholesterol (5.5 +/- 1.6 vs. 5.3 +/- 1.5 mmol/L), and decreased albumin (37.8 +/- 5.4 vs. 38.9 +/- 5.3 g/L), prealbumin (317 +/- 91 vs. 340 +/- 94 mg/L), creatinine (711 +/- 184 vs. 816 +/- 217 micromol/L) and LBM (76 +/- 18 vs. 87 +/- 21%). Normalized protein catabolic rate was similar in the two groups (1.11 +/- 0.31 vs. 1.13 +/- 0.32 g/kg/L). One and two-year survival was 83.7 +/- 2.9% and 65.5 +/- 3.8% in diabetic patients versus 90.3 +/- 0.8% and 79.9 +/- 1.1% in non-diabetics (relative risk 1.26, P < 0.01). Independent predictors of survival were age, albumin and prealbumin in non-diabetics and only age in diabetics. CONCLUSION: Diabetic patients compared to non-diabetics were characterized by an increased incidence of protein malnutrition and decreased survival. However, the higher death risk associated with diabetes was not related to malnutrition.