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Let Them Eat During Dialysis: An Overlooked Opportunity to Improve Outcomes in Maintenance Hemodialysis Patients

2013; Elsevier BV; Volume: 23; Issue: 3 Linguagem: Inglês

10.1053/j.jrn.2012.11.001

1532-8503

Kamyar Kalantar‐Zadeh, T. Alp İkizler,

Muscle and Compartmental Disorders

In individuals with chronic kidney disease, surrogates of protein-energy wasting, including a relatively low serum albumin and fat or muscle wasting, are by far the strongest death risk factor compared with any other condition. There are data to indicate that hypoalbuminemia responds to nutritional interventions, which may save lives in the long run. Monitored, in-center provision of high-protein meals and/or oral nutritional supplements during hemodialysis is a feasible, inexpensive, and patient-friendly strategy despite concerns such as postprandial hypotension, aspiration risk, infection control and hygiene, dialysis staff burden, diabetes and phosphorus control, and financial constraints. Adjunct pharmacologic therapies can be added, including appetite stimulators (megesterol, ghrelin, and mirtazapine), anabolic hormones (testosterone and growth factors), antimyostatin agents, and antioxidative and anti-inflammatory agents (pentoxiphylline and cytokine modulators), to increase efficiency of intradialytic food and oral supplementation, although adequate evidence is still lacking. If more severe hypoalbuminemia (<3.0 g/dL) not amenable to oral interventions prevails, or if a patient is not capable of enteral interventions (e.g., because of swallowing problems), then parenteral interventions such as intradialytic parenteral nutrition can be considered. Given the fact that meals and supplements during hemodialysis would require only a small fraction of the funds currently used for dialysis patients this is also an economically feasible strategy. In individuals with chronic kidney disease, surrogates of protein-energy wasting, including a relatively low serum albumin and fat or muscle wasting, are by far the strongest death risk factor compared with any other condition. There are data to indicate that hypoalbuminemia responds to nutritional interventions, which may save lives in the long run. Monitored, in-center provision of high-protein meals and/or oral nutritional supplements during hemodialysis is a feasible, inexpensive, and patient-friendly strategy despite concerns such as postprandial hypotension, aspiration risk, infection control and hygiene, dialysis staff burden, diabetes and phosphorus control, and financial constraints. Adjunct pharmacologic therapies can be added, including appetite stimulators (megesterol, ghrelin, and mirtazapine), anabolic hormones (testosterone and growth factors), antimyostatin agents, and antioxidative and anti-inflammatory agents (pentoxiphylline and cytokine modulators), to increase efficiency of intradialytic food and oral supplementation, although adequate evidence is still lacking. If more severe hypoalbuminemia (<3.0 g/dL) not amenable to oral interventions prevails, or if a patient is not capable of enteral interventions (e.g., because of swallowing problems), then parenteral interventions such as intradialytic parenteral nutrition can be considered. Given the fact that meals and supplements during hemodialysis would require only a small fraction of the funds currently used for dialysis patients this is also an economically feasible strategy. This article has an online CPE activity available at www.kidney.org/professionals/CRN/ceuMain.cfmIntroductionOvernutrition is a major problem in the general population and a serious risk of metabolic syndrome, cardiovascular disease, and chronic kidney disease (CKD), with subsequent increased death risk. However, in CKD patients, this relationship may be different, especially in those who undergo maintenance dialysis treatment. In the latter patient population, so-called "uremic malnutrition"1Pupim L.B. Caglar K. Hakim R.M. et al.Uremic malnutrition is a predictor of death independent of inflammatory status.Kidney Int. 2004; 66: 2054-2060Crossref PubMed Scopus (144) Google Scholar (or "malnutrition-inflammation complex"2Kalantar-Zadeh K. Ikizler T.A. Block G. et al.Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences.Am J Kidney Dis. 2003; 42: 864-881Abstract Full Text Full Text PDF PubMed Scopus (729) Google Scholar or "renal cachexia"3Mak R.H. Ikizler A.T. Kovesdy C.P. et al.Wasting in chronic kidney disease.J Cachexia Sarcopenia Muscle. 2011; 2: 9-25Crossref PubMed Scopus (4) Google Scholar), which is recently also referred to as "protein-energy wasting" (PEW),4Fouque 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: 391-398Crossref PubMed Scopus (1246) Google Scholar is by far the strongest risk factor for adverse outcomes and death,5Kovesdy C.P. Kalantar-Zadeh K. Why is protein-energy wasting associated with mortality in chronic kidney disease?.Semin Nephrol. 2009; 29: 3-14Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar whereas surrogates of overnutrition such as obesity or hyperlipidemia appear counterintuitively protective.6Kalantar-Zadeh K. Kovesdy C.P. Derose S.F. et al.Racial and survival paradoxes in chronic kidney disease.Nat Clin Pract Nephrol. 2007; 3: 493-506Crossref PubMed Scopus (92) Google Scholar Similar associations have been described in individuals with other chronic disease states such as heart failure7Oreopoulos A. Padwal R. Kalantar-Zadeh K. et al.Body mass index and mortality in heart failure: a meta-analysis.Am Heart J. 2008; 156: 13-22Abstract Full Text Full Text PDF PubMed Scopus (606) Google Scholar or in the geriatric populations.8Oreopoulos A. Kalantar-Zadeh K. Sharma A.M. et al.The obesity paradox in the elderly: potential mechanisms and clinical implications.Clin Geriatr Med. 2009; 25 (viii): 643-659Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar It is believed that in CKD and other chronic diseases that are associated with wasting syndrome, pathophysiologic pathways related to malnutrition act as short-term killers and render such long-term killers as obesity or hypertension practically irrelevant. In other words, dialysis patients die much faster of short-term consequences of PEW so that they do not live long enough to die of the long-term consequences of overnutrition. This so-called time-discrepancy hypothesis9Kalantar-Zadeh K. Block G. Horwich T. et al.Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure.J Am Coll Cardiol. 2004; 43: 1439-1444Abstract Full Text Full Text PDF PubMed Scopus (529) Google Scholar suggests that in CKD patients whose short-term mortality is high, interventions that can improve their nutritional status and prevent or correct wasting and sarcopenia have the potential to save lives.10Kalantar-Zadeh K. Abbott K.C. Salahudeen A.K. et al.Survival advantages of obesity in dialysis patients.Am J Clin Nutr. 2005; 81: 543-554PubMed Google Scholar In addition to longevity, nutritional status is a strong predictor of better health-related quality of life in dialysis patients.11Feroze U. Noori N. Kovesdy C.P. et al.Quality-of-life and mortality in hemodialysis patients: roles of race and nutritional status.Clin J Am Soc Nephrol. 2011; 6: 1100-1111Crossref PubMed Scopus (88) Google ScholarPEW and MortalityIf the PEW is such as strong death risk factor, one would expect that the PEW surrogates such as low serum albumin or lower protein intake correlate with mortality. Indeed, evidence suggests that they do. A low serum albumin concentration is by far the strongest predictor of mortality and poor outcomes in dialysis patients when compared with any other risk factors,12Lacson Jr., E. Wang W. Hakim R.M. et al.Associates of mortality and hospitalization in hemodialysis: potentially actionable laboratory variables and vascular access.Am J Kidney Dis. 2009; 53: 79-90Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar, 13Beddhu S. Kaysen G.A. Yan G. et al.Association of serum albumin and atherosclerosis in chronic hemodialysis patients.Am J Kidney Dis. 2002; 40: 721-727Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar be it the traditional risk factors (hypertension, hypercholesterolemia, diabetes, obesity) or nonconventional ones (anemia measures, minerals and bone surrogates, dialysis treatment and technique).5Kovesdy C.P. Kalantar-Zadeh K. Why is protein-energy wasting associated with mortality in chronic kidney disease?.Semin Nephrol. 2009; 29: 3-14Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar The sensitivity of serum albumin to predict CKD patient outcomes is relatively high with such a granularity of as little as 0.2 g/dL or even smaller.14Kalantar-Zadeh K. Kilpatrick R.D. Kuwae N. et al.Revisiting mortality predictability of serum albumin in the dialysis population: time dependency, longitudinal changes and population-attributable fraction.Nephrol Dial Transplant. 2005; 20: 1880-1888Crossref PubMed Scopus (285) Google Scholar, 15Lacson Jr., E. Ikizler T.A. Lazarus J.M. et al.Potential impact of nutritional intervention on end-stage renal disease hospitalization, death, and treatment costs.J Ren Nutr. 2007; 17: 363-371Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar, 16Mehrotra R. Duong U. Jiwakanon S. et al.Serum albumin as a predictor of mortality in peritoneal dialysis: comparisons with hemodialysis.Am J Kidney Dis. 2011; 58: 418-428Abstract Full Text Full Text PDF PubMed Scopus (173) Google Scholar, 17Molnar M.Z. Kovesdy C.P. Bunnapradist S. et al.Associations of pretransplant serum albumin with post-transplant outcomes in kidney transplant recipients.Am J Transplant. 2011; 11: 1006-1015Crossref PubMed Scopus (65) Google Scholar In other words, a dialysis patient with a baseline serum albumin of even 0.2 g/dL higher or lower than another patient with similar demographic and comorbidity constellations has a significantly lower or higher death risk, respectively. The albumin-death association is highly incremental and linear with virtually no cutoff level below or above which the association with survival would cease or reverse.14Kalantar-Zadeh K. Kilpatrick R.D. Kuwae N. et al.Revisiting mortality predictability of serum albumin in the dialysis population: time dependency, longitudinal changes and population-attributable fraction.Nephrol Dial Transplant. 2005; 20: 1880-1888Crossref PubMed Scopus (285) Google Scholar, 15Lacson Jr., E. Ikizler T.A. Lazarus J.M. et al.Potential impact of nutritional intervention on end-stage renal disease hospitalization, death, and treatment costs.J Ren Nutr. 2007; 17: 363-371Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar This is in sharp contradistinction to most other outcome predictors in CKD with U- or J-shape survival associations. Even more important to note is that changes in serum albumin over time are associated with proportional and reciprocal alterations in subsequent death risk in that a rise or drop in serum albumin by as little as 0.1 g/dL over a few month period is associated with improving or worsening survival, respectively.14Kalantar-Zadeh K. Kilpatrick R.D. Kuwae N. et al.Revisiting mortality predictability of serum albumin in the dialysis population: time dependency, longitudinal changes and population-attributable fraction.Nephrol Dial Transplant. 2005; 20: 1880-1888Crossref PubMed Scopus (285) Google Scholar Similar mortality predictabilities have also been reported with other nutritional markers such as serum prealbumin18Rambod M. Kovesdy C.P. Bross R. et al.Association of serum prealbumin and its changes over time with clinical outcomes and survival in patients receiving hemodialysis.Am J Clin Nutr. 2008; 88: 1485-1494Crossref PubMed Scopus (106) Google Scholar (e.g., <30 mg/dL) and the "malnutrition-inflammation score" (MIS ≥ 5).19Rambod M. Bross R. Zitterkoph J. et al.Association of Malnutrition-Inflammation Score with quality of life and mortality in hemodialysis patients: a 5-year prospective cohort study.Am J Kidney Dis. 2009; 53: 298-309Abstract Full Text Full Text PDF PubMed Scopus (246) Google Scholar Nevertheless, serum albumin remains the simple single test that is readily available ubiquitously and has been recommended by most nutritional societies as a first-line nutritional marker. Hence, as shown in Table 1, a diverse array of nutritional and dietary interventions are often considered for maintenance hemodialysis patients with serum albumin less than 4.0 g/dL or other signs of PEW.Table 1Suggested Intervention for Maintenance Hemodialysis Patients With Serum Albumin <4.0 g/dL or Other Signs of PEWOral Nutritional InterventionsIn-Center, Intradialytic AdministrationAdvantagesDisadvantagesMeals during dialysis treatmentPreferred as routine for all hemodialysis patientsSee Table 2See Table 2ONSPreferred especially if meals not effectiveSee Table 2See Table 2Tube feeding (via temporary nasogastric tubing or PEG)In- and off-center if oral nutrition not possibleConvenient accessCan only be used for fluid supplementsParenteral IDPNPreferred especially if albumin is <3.0 g/dLConvenientOffered only 3 times/wk Total parenteral nutritionUsually administered off-dialysis clinicCan be used more frequently than IDPNRequires an extra access line (e.g., PICC line)Pharmacologic Appetite stimulatorsTo improve adherence∗Not clear whether intradialytic (in-center) administration can offer any benefit beyond improving adherence to high-protein diet and supplements, including during hemodialysis therapy.Enhances protein/energy intakeMay aggravate obesity; more fat accumulation than muscle? AntidepressantTo improve adherence∗Not clear whether intradialytic (in-center) administration can offer any benefit beyond improving adherence to high-protein diet and supplements, including during hemodialysis therapy.May improve appetiteKnown side effects Anti-inflammatory and/or antioxidativeTo improve adherence∗Not clear whether intradialytic (in-center) administration can offer any benefit beyond improving adherence to high-protein diet and supplements, including during hemodialysis therapy.May improve inflammatory/oxidative profileLimited studies; unknown side effects Anabolic hormonesTo improve adherence∗Not clear whether intradialytic (in-center) administration can offer any benefit beyond improving adherence to high-protein diet and supplements, including during hemodialysis therapy.May enhance muscle accretion rather than fatAdverse events associated with anabolic steroid Antimyostatin and/or other muscle-enhancing agentsTo improve adherence∗Not clear whether intradialytic (in-center) administration can offer any benefit beyond improving adherence to high-protein diet and supplements, including during hemodialysis therapy.May enhance muscle accretionLimited human studies, unknown side effect profileOther Interventions Dialysis techniqueNAImplemented as a part of routine treatment renovationMay cost more when compared with older techniques Dialysis treatment factorsNAImplemented during routine treatmentCosts/benefits should be weighed Intradialytic exercisePreferredImproves muscle mass and functionRequires instrument provision and maintenance; technically might be challengingNA, not applicable; PEG, percutaneous endoscopic gastrostromy; PICC, peripherally inserted central catheter.∗ Not clear whether intradialytic (in-center) administration can offer any benefit beyond improving adherence to high-protein diet and supplements, including during hemodialysis therapy. Open table in a new tab Meals and Oral Supplements During Hemodialysis TreatmentGiven the exceptionally high dietary protein requirement of dialysis patients (∼1.2 g/kg/day), and given the observation that most dialysis patients eat less than 1.0 g/kg/day of protein,20Shinaberger C.S. Greenland S. Kopple J.D. et al.Is controlling phosphorus by decreasing dietary protein intake beneficial or harmful in persons with chronic kidney disease?.Am J Clin Nutr. 2008; 88: 1511-1518Crossref PubMed Scopus (256) Google Scholar an average dialysis patient needs an additional 0.2 to 0.4 g/kg/day of protein supplement21Kalantar-Zadeh K. Cano N.J. Budde K. et al.Diets and enteral supplements for improving outcomes in chronic kidney disease.Nat Rev Nephrol. 2011; 7: 369-384Crossref PubMed Scopus (128) Google Scholar (see Fig. 1). Inadequate food intake, especially during hemodialysis treatment days, is a common practice among U.S. dialysis patients, whereas in many other countries meals are routinely served during the hemodialysis treatment sessions. Table 2 summarizes some of the pros and cons pertaining to in-center (in the dialysis clinic) monitored eating and the provision of meals during hemodialysis treatments. In a recent online survey, when we asked nephrologists and dialysis centers in the United States as to why meal trays for patients do not exist during hemodialysis treatment, the common stated concerns include (1) postprandial hypotension; (2) risk of choking or aspiration; (3) infection control and hygiene issues, including fear of fecal-oral transmission of such diseases as hepatitis A; (4) staff burden and distraction; and (5) diabetes and phosphorus control (see Table 2).21Kalantar-Zadeh K. Cano N.J. Budde K. et al.Diets and enteral supplements for improving outcomes in chronic kidney disease.Nat Rev Nephrol. 2011; 7: 369-384Crossref PubMed Scopus (128) Google Scholar It is not unusual to hear statements such as "They get food everywhere and this is not fair to the next patient that has to sit in their crumbs," "I don't want another lawsuit for choking while eating on dialysis" and "Having a full stomach might complicate their management."22Kalantar-Zadeh K. Why not meals during dialysis?.Ren Urol News. 2009; 9: 4Google Scholar On the other hand, meals are routinely given to dialysis outpatients in most European and Southeast Asian countries. German dialysis patients invariably eat during their hemodialysis treatments and have higher serum albumin and greater survival than their U.S. counterparts.23Wizemann V. Regular dialysis treatment in Germany: the role of non-profit organisations.J Nephrol. 2000; 13: S16-S19PubMed Google Scholar In the past, meals on dialysis were also routine in the United States. Indeed, a few Veteran Administration hospitals still provide meal trays, including breakfast, lunch, or supper, during all dialysis shifts, be it inpatient or outpatient.Table 2Pros and Cons of In-Center (in the Dialysis Clinic) Monitored Eating and Provision of Meals During Hemodialysis TreatmentsProsConsImpact on nutritional status and clinical outcomes•Meals during HD are practiced routinely in many industrialized nations including Europe and Southeast Asia•Excellent survival in most countries where meals are served during HD•No major unfavorable outcomes reported in countries offering meals during HDLow blood pressure and labile circulation during food ingestion•Blood pressure may be lowered during and after eating because of splanchnic circulation expansion even with new dialysis treatment and techniques•Hypotensive episode may lead to shortening dialysis treatment or less efficient fluid removalMitigates/corrects intra- and postdialysis catabolism•HD treatment exerts catabolic effects that can be avoided by eating during HD•Muscle wasting may be mitigated•Effectively increases the frequency of daily meal intakesRisk of aspiration and other respiratory complications•Risk of choking is likely higher in patients with a history of neurologic disorders, swallowing problems, or other disabilities•Even in sitting position aspiration may happen in patient who cannot feed themselves at homeBetter control of dietary phosphorus, potassium, salt, and fluid•In-center meals and supplements can be more optimally prepared for the specific needs of CKD patients•In-center meals may improve adherence to restricted salt and fluid intake•Intake of phosphorus binder can be monitored•Improved patient education can be achieved by simultaneous interaction with dietitian and nephrologist while eatingInfectious control and hygiene issues•Fecal–oral transmission of infection including hepatitis A possible•Food crumbs may lead to infestation•Risk if ingestion of rotten food and food poisoning is possible•Meal tray delivery and storage may pose additional hygiene challengesIncreased adherence with HD treatment•Increases the likelihood of attending HD treatment•May mitigate the likelihood of HD treatment shortening by hungry patients•Enhances communication among patients, dietitians, and other clinic staffBurden on dialysis staff and logistics constraints•Overworked dialysis staff faced with additional responsibilities•Providing nutrition may not be regarded as an a justifiable part of patient care in dialysis clinicsImproved patient satisfaction and quality of life•In-center meals may make patients more content with dialysis treatment lifestyle•Improved quality of life by means of in-center meal may improve survivalOnly a fraction of required meals are provided•Thrice-weekly meals account for 15% of all meals•The evidence that catabolic effect of HD can be mitigated or reversed by intradialytic nutrition is not convincingRelatively low costs of meals on HD•The costs of providing in-center meals is a small fraction of expensive medications used in end-stage renal disease•Dialysis organizations can adapt this in the form of efficient and economical approachesAdded expenses to dialysis treatment•The costs of meals during dialysis may be small but still not negligible•If costs of meals are factored in by the insurance company or in the bundling equation, this may be at the cost of other more critical treatment components and medicationsHD, hemodialysis. Open table in a new tab Despite the traditional concerns of North American nephrologists and dialysis care providers, the positive development is that over the past few years increasing numbers of dialysis clinics have allowed and even encourage oral nutritional supplementation during the treatment. Indeed, several recent pilot and nonrandomized studies have indicated that provision of oral nutritional supplements with high protein content during hemodialysis has improved serum albumin.24Pupim L.B. Majchrzak K.M. Flakoll P.J. et al.Intradialytic oral nutrition improves protein homeostasis in chronic hemodialysis patients with deranged nutritional status.J Am Soc Nephrol. 2006; 17: 3149-3157Crossref PubMed Scopus (127) Google Scholar, 25Caglar K. Fedje L. Dimmitt R. et al.Therapeutic effects of oral nutritional supplementation during hemodialysis.Kidney Int. 2002; 62: 1054-1059Crossref PubMed Scopus (146) Google Scholar, 26Sundell M.B. Cavanaugh K.L. Wu P. et al.Oral protein supplementation alone improves anabolism in a dose-dependent manner in chronic hemodialysis patients.J Ren Nutr. 2009; 19: 412-421Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 27Kovesdy C.P. Kalantar-Zadeh K. Oral bicarbonate: renoprotective in CKD?.Nat Rev Nephrol. 2010; 6: 15-17Crossref PubMed Scopus (8) Google Scholar Indeed, an elaborate metabolic study showed 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 (Fig. 2).24Pupim L.B. Majchrzak K.M. Flakoll P.J. et al.Intradialytic oral nutrition improves protein homeostasis in chronic hemodialysis patients with deranged nutritional status.J Am Soc Nephrol. 2006; 17: 3149-3157Crossref PubMed Scopus (127) Google Scholar We would also argue that in addition to improving nutritional status, providing in-center meals and/or oral nutritional supplements during hemodialysis treatment would improve patient compliance and satisfaction (Table 2). Patients may be more motivated to attend the treatments when they know that a lunchbox is awaiting them. Although in Europe meals on dialysis rarely lead to hypotension, we would argue that it can be considered as an effective strategy against intradialytic hypertension. Many patients may already ignore the eating-prohibitory regulations of some dialysis clinics and still bring in their own foods, including ones with high phosphorus content and super-sized soft drinks. Hence, we are in the position to offer them a better and more appropriate food or supplement with higher protein content, lower phosphorus-to-protein ratio,28Noori N. Kalantar-Zadeh K. Kovesdy C.P. et al.Association of dietary phosphorus intake and phosphorus to protein ratio with mortality in hemodialysis patients.Clin J Am Soc Nephrol. 2010; 5: 683-692Crossref PubMed Scopus (155) Google Scholar and lower potassium content.29Noori N. Kalantar-Zadeh K. Kovesdy C.P. et al.Dietary potassium intake and mortality in long-term hemodialysis patients.Am J Kidney Dis. 2010; 56: 338-347Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar The in-center food can be offered along with directly observed administration of phosphorus binder regimen and the required multivitamins at the time of meal or supplement intake.Figure 2Anabolic effects of oral versus parenteral nutrition during hemodialysis treatment to justify preference for meals and oral supplements during hemodialysis treatment.Adapted from Kalantar-Zadeh et al.21Kalantar-Zadeh K. Cano N.J. Budde K. et al.Diets and enteral supplements for improving outcomes in chronic kidney disease.Nat Rev Nephrol. 2011; 7: 369-384Crossref PubMed Scopus (128) Google Scholar and Pupim et al.24Pupim L.B. Majchrzak K.M. Flakoll P.J. et al.Intradialytic oral nutrition improves protein homeostasis in chronic hemodialysis patients with deranged nutritional status.J Am Soc Nephrol. 2006; 17: 3149-3157Crossref PubMed Scopus (127) Google ScholarView Large Image Figure ViewerDownload Hi-res image Download (PPT)There are several studies in which oral nutrition has been provided during hemodialysis treatment, including studies by Szklarek-Kubicka et al.30Szklarek-Kubicka M. Fijalkowska-Morawska J. Zaremba-Drobnik D. et al.Effect of intradialytic intravenous administration of omega-3 fatty acids on nutritional status and inflammatory response in hemodialysis patients: a pilot study.J Ren Nutr. 2009; 19: 487-493Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar and Moreira et al.31Moreira A.C. Gaspar A. Serra M.A. et al.Effect of a sardine supplement on C-reactive protein in patients receiving hemodialysis.J Ren Nutr. 2007; 17: 205-213Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar In a more recent controlled trial known as the Anti-Inflammatory and Anti-Oxidative Nutrition during Dialysis (AIONID) study,32Rattanasompattikul M. Molnar M.Z. Lee M.L. 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; ([in press])PubMed Google Scholar 84 adult hypoalbuminemic (albumin < 4.0 g/dL) 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; these 4 groups were associated with an average change in serum albumin of +0.21 (P = .004), +0.14 (P = .008), +0.18 (P = .001), and +0.03 g/dL (P = .59), respectively. However, in a predetermined intention-to-treat regression analysis, only ONS during hemodialysis without pentoxifylline was associated with a significant albumin rise (+0.17 ± 0.07 g/dL, P = .018).32Rattanasompattikul M. Molnar M.Z. Lee M.L. 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; ([in press])PubMed Google Scholar In two recent large observational studies, ONS during hemodialysis was associated with improved survival33Lacson Jr., E. Wang W. Zebrowski B. et al.Outcomes associated with intradialytic oral nutritional supplements in patients undergoing maintenance hemodialysis: a quality improvement report.Am J Kidney Dis. 2012; 60: 591-600Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar and improved hospitalization.34Cheu C. Pearson J. Dahlerus C. et al.Association between oral nutritional supplementation and clinical outcomes among patients with ESRD.Clin J Am Soc Nephrol. 2012 Oct 18; ([Epub ahead of print])PubMed Google Scholar In another recent randomized controlled trial, the Fosrenol for Enhancing Dietary Protein Intake in Hypoalbuminemic Dialysis Patients (FrEDI) study35Koontz T. Balikian S. Bross R. et al.Fosrenol for Enhancing Dietary Protein Intake in Hypoalbuminemic Dialysis Patients (FrEDI) study.Kidney Res Clin Pract. 2012; 31 ([abstract]): A68Abstract Full Text PDF Google Scholar (ClinicalTrials.gov # NCT0111694110), in which 110 hypoalbuminemic (<4.0 mg/dL) hemodialysis patients received meals during hemodialysis for 8 weeks, the intervention group received high-protein meals as prepared meal boxes (50 g protein, 850 Cal, phosphorus-to-protein ratio < 10 mg/g) along with 0.5 to 1.5 g lanthanum carbonate (Fosrenol) titrated as needed to control phosphorus burden from the high-protein meals, whereas the control group received low-calorie (<50 Cal) meal boxes containing almost no protein (<1 g, such as salads) during each hemodialysis treatment. Among the 51 intervention and 55 control subjects who qualified for the intention-to-treat analyses, the combined rise in albumin of 0.2 g/dL or greater while maintaining phosphorus in the range of 3.5 to less than 5.5 mg/dL was achieve