Preventing Protein Energy Wasting In Patients On Maintenance Dialysis

Anita Saxena

Editor, Journal of Renal Nutrition & Metabolism

“Uremic malnutrition, renal cachexia or protein-energy wasting” (PEW), are strongest risk factor for adverse outcomes, hospitalization and death in patients on maintenance. Protein energy wasting most likely sets in chronic kidney disease (CKD) stage 3 (GFR<60ml/minute) or even earlier, which causes spontaneous diminished dietary protein and energy intake. The long journey between CKD stage 3 and stage CKD5D with intermittent infections and persistently inadequate energy and protein intake along with restricted diets is an important cause of malnutrition at initiation of dialysis. Studies by Chung et al have shown that survival and relative risk of death increases in patients who are malnourished compared to those have normal nutritional status. Low serum albumin concentration is a strong predictor of mortality and poor outcomes in dialysis patients when compared to any other risk factors although serum albumin is effected both by nutritional and non nutritional factors. A multitude of factors can affect the nutritional and metabolic status of patients with CKD, including uremia which causes decreased dietary nutrient intake, reduced essential amino acids, catabolic effects of renal replacement therapy, systemic inflammation response syndrome (SIRS), metabolic and hormonal derangements, acidemia and comorbid conditions such as diabetes, altered sleep pattern and depression. These conditions call for regular assessment of nutritional status in order to prevent progression of PEW.

Nutritional assessment must include periodic dietary interviews, anthropometry (to diagnose depletion of fat and muscle) iron profile (to ensure optimal ESA dose) and lipid profile (to treat hypocholestrolemia), to ensure patient is clinically stable and not losing muscle or fat mass.


Address for Correspondence

Dr Anita Saxena, Editor, JRNM Additional Professor,

Department Of Nephrology, SGPGIMS, Lucknow. 226014. INDIA


Hydration state of the patient is important because of four main factors: i)volume expansion is a major cause of hypertension in CKD patients, and nearly all CKD patients are hypertensive upon the initiation of dialysis.

ii) volume overload correlates with cardiovascular risk factors in patients with CKD iii) strong association between malnutrition–inflammation complex syndrome (MICS) and volume overload is documented, and iv) overhydration has a strong and positive association with proteinuria. With worsening cardiac status, gut hypoxia ensues and patient’s appetite worsens. Management of gastroparesis is important and should include correction of nutritional state, relief of symptoms, improvement of gastric emptying and, in diabetics, glycemic control. If oral intake is not adequate, then enteral nutrition via jejunostomy tube needs to be considered. Parenteral nutrition is required when hydration and nutritional state cannot be maintained. Medical treatment entails use of prokinetic and antiemetic therapies. Current approved treatment options, including metoclopramide and gastric electrical stimulation (GES, approved on a humanitarian device exemption), do not adequately address clinical need. Antiemetics have not been specifically tested in gastroparesis, but they may relieve nausea and vomiting. Other medications aimed at symptom relief include unapproved medications or off- label indications, and include domperidone, erythromycin (primarily over a short term), and centrally acting antidepressants used as symptom modulators.

Hence, nutritional intervention is of utmost importance in preventing PEW. Through dietary interviews, a dietician should evaluate whether patient is taking 1.2g/kg/d of protein if on maintenance hemodialysis and 1.3 g/kg/d of protein if on peritoneal dialysis (PD) and 30-35 kcal/kg/d of energy. Dedicated renal dieticians should follow patients through telephonic interviews and motivate patients to adhere to dietary advise.

Nutritional supplementation, administered orally, enterally, or parenterally, is effective in replenishing protein


and energy stores in patients in whom meals alone cannot help maintain adequate nutritional status. Oral nutritional supplements should be given in between two meals. Provision of intradialytic proteinrich snacks can help prevent dialysis induced muscle catabolism. A metabolic study has shown that oral protein intake during hemodialysis therapy is effective in opposing the catabolic effect of hemodialysis treatment that would otherwise last even hours after the therapy ended. Over the past few years increasing numbers of dialysis clinics are encourage oral nutritional supplements during the dialysis treatment. Recent pilot and non-randomized studies have indicated that provision of oral nutritional supplements with high protein content during hemodialysis improves serum albumin. In a controlled trial “Anti-Inflammatory and Anti-Oxidative Nutrition during Dialysis” (AIONID) Study, 84 adult hypoalbuminemic (albumin<4.0 g/dL) 84 hemodialysis patients were double-blindly randomized to receive 16 weeks of interventions including oral nutritional supplement (ONS), pentoxifylline, ONS with pentoxifylline, or placebos during hemodialysis treatments. In all the 4 groups improvement in serum albumin was observed. In another large randomized observational study “Fosrenol for Enhancing Dietary Protein Intake in Hypoalbuminemic Dialysis Patients” (FrEDI) Study, provision of high protein meals combined with a potent binder during hemodialysis treatment was safe and improved serum albumin while controlling serum phosphorus. Hence patients should be motivated to bring lunchbox with them which will also be an effective strategy against intradialytic hypertension. The meal should be followed by a phosphate binder. Multivitamins should be given after termination of dialysis treatment. Patients who are prone to going into intradialytic hypotension should not take antihypertensive medication prior to start of dialysis, their interdialytic weight gain should be monitored along with fluid intake and should avoid meal during dialysis. Such patients should be closely monitored for symptoms like, sweating, intradialytic cramping, nausea, vomiting, headache and chest discomfort.

Appetite stimulants (megesterol ghrelin, and mirtazapine), anti-inflammatory interventions (pentoxiphylline and cytokine modulatory agents, or omega-3 fatty acid), and neweranabolicagents(testosteroneandgrowthfactors) along with exercise are emerging as novel therapies in combination with nutritional supplementation. These interventions have been shown to improve protein stores and are being considered as potential approaches for the treatment of PEW. Chronic inflammation can predispose advanced CKD patients to a catabolic state leading to worsening of protein- energy wasting by both increasing protein breakdown and decreasing protein synthesis. Routine administration of


nutritional supplementation, both parenterally and orally, improves nutritional status even in inflamed hemodialysis patients.

However, if patient is not capable of enteral interventions, then intra-dialytic parenteral nutrition (IDPN) should be considered on every dialysis treatment. In PD patients IDAA canbeused. Severalstudieshaveshownthat IDPNisespecially effective in hypoalbuminimic patients. Refer to two articles on IDPN in this issue. Non-nutritional interventions such as dialysis treatment modalities and techniques that lead to less inflammation or protein loss should be considered.



  1. Pupim LB, Caglar K, Hakim RM, et al. Uremic malnutrition is a predictor of death independent of inflammatory status. Kidney Int. 2004;66:2054–2060.

  2. Kalantar-Zadeh K, Ikizler TA, Block G, et al. Malnutrition- inflammation complex syndrome in dialysis patients: Causes and consequences. Am J Kidney Dis. 2003;42:864–881.

  3. Mak RH, Ikizler AT, Kovesdy CP, et al. Wasting in chronic kidney disease. J Cachex Sarcopenia Muscle. 2011;2:9–25.

  4. Fouque D, Kalantar-Zadeh K, Kopple J, et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int. 2008;73:391–398.

  5. Collins AJ, Foley RN, Herzog C et al. United States Renal Data System 2008 Annual Data Report. Am J Kidney Dis 2009; 53: S1–S374 Kidney International (2014) 85, 703–709; doi:10.1038/ki.2013.336; published online 11 September 2013

  6. Szu-Chun Hung, Ko-Lin Kuo, Ching-Hsiu Peng, Che-Hsiung Wu etal Volume overload correlates with cardiovascular risk factors in patients with chronic kidney disease Kidney International (2014) 85, 703–709

  7. Pupim LB, Majchrzak KM, Flakoll PJ, et al. Intradialytic oral nutrition improves protein homeostasis in chronic hemodialysis patients with deranged nutritional status. J Am Soc Nephrol. 2006;17:3149–3157.

  8. Caglar K, Fedje L, Dimmitt R, et al. Therapeutic effects of oral nutritional supplementation during hemodialysis. Kidney Int. 2002;62:1054–1059.

  9. Sundell MB, Cavanaugh KL, Wu P, et al. Oral protein supplementation alone improves anabolism in a dose-dependent manner in chronic hemodialysis patients. J Ren Nutr. 2009;19:412–421.

  10. Kovesdy CP, Kalantar-Zadeh K. Oral bicarbonate: renoprotective in CKD? Nat Rev Nephrol. 2010;6:15–17

  11. Koontz T, Balikian S, Bross R, et al. Fosrenol for Enhancing Dietary Protein Intake in Hypoalbuminemic Dialysis Patients (FrEDI) Study. Kidney Research and Clinical Practice. 2012;31:A68

  12. Rattanasompattikul M, Molnar MZ, Lee ML, et al. Anti-Inflammatory and Anti-Oxidative Nutrition in Hypoalbuminemic Dialysis Patients (AIONID) Study: Results of the Pilot-Feasibility Double-Blind Randomized Placebo-Controlled Trial. J Cachexia Sarcopenia Muscle. 2013