Moorthi, Ranjani N.

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Does an Apple (or Many) Each Day, Keep Mortality Away?

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Clin J Am Soc Nephrol. 2019 Feb 7; 14(2): 180–181.Published online 2019 Jan 31.doi: 10.2215/CJN.15001218: 10.2215/CJN.15001218PMCID: PMC6390917Does an Apple (or Many) Each Day, Keep Mortality Away?Ranjani N. MoorthiDivision of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IndianaCorresponding author.Correspondence: Dr. Ranjani N. Moorthi, Division of Nephrology, Department of Medicine, Indiana UniversitySchool of Medicine, 950 W. Walnut Street, R2-202, Indianapolis, IN 46202. Email: ude.ui@ihtroomrKeywords: Vegetables, Fruit, Cohort Studies, dialysis, Surveys and Questionnaires, Risk, cardiovascular diseaseCopyright © 2019 by the American Society of NephrologyIn this issue of the Clinical Journal of the American Society of Nephrology, Saglimbene et al. (1) highlightthe importance of fruit and vegetable intake in 9757 patients undergoing dialysis across 11 European andSouth American countries by demonstrating that a higher number of fruits and vegetables consumed perweek is associated with lower risk of all cause and noncardiovascular mortality. Assessment of intake wasby self-report by asking two questions that are part of the GA LEN questionnaire—“How often did you eatfresh fruit during the previous year?” and “How often did you eat any vegetables (excluding potatoes)during the previous year?”—at a single point in time. Patients were followed for a median 2.7 years and theprimary outcome of mortality was coded as “cardiovascular” and “noncardiovascular.” The authors showthat in comparison to two servings of fruits and vegetables per week, 17 servings per week are associatedwith a 20% lower hazard of all-cause mortality, the primary outcome (HR, 0.80; 95% CI, 0.71 to 0.91) anda 23% lower hazard of noncardiovascular mortality (HR, 0.77; 95% CI, 0.66 to 0.91), with no significantrelationship with cardiovascular mortality, which is surprising, given the purported benefits of fruits andvegetables, but mirrors findings in a large cohort study in the general population (2).The putative benefits of fruit and vegetable intake include benefits to BP, lipid control, and improvementsin endothelial function and insulin sensitivity. Despite these benefits, typical intakes of fruits andvegetables tend to fall far short of recommendations even in the general population. The Dietary Guidelinesfor Americans 2015–2020, as well as various European guidelines, recommend four to five servings offruits and vegetables daily (3). But, in a general population cohort of 135,335 adults from 18 countries,only 30% ate more than the recommended four servings a day (2). However, Saglimbene et al. show thatthis deficit is a far cry from that of patients on prevalent hemodialysis. In this study, only 4% of participantsate more than a median of four servings daily. As a result of this poor daily intake, overall fruit andvegetable consumption in patients on hemodialysis had to be expressed as servings per week in thisanalysis, to even be meaningful. The overall median combined fruit and vegetable intake was only amedian of eight servings per week, with variability across countries surveyed.Inadequate fruit and vegetable intake may be a lifelong habit in some individuals, but the findings from thisstudy demonstrate that it is dramatically lower in those on hemodialysis compared with the generalpopulation. As the authors point out, patients undergoing hemodialysis are routinely advised to eat a diet2Does an Apple (or Many) Each Day, Keep Mortality Away? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390917/?report=printable1 of 4 4/13/2020, 2:48 PMincluding 2 g potassium per day. Patient education materials often include food lists categorizingpotassium-containing foods. Foods listed as “high potassium” or >200 mg per serving, the majority ofwhich are fruits and vegetables, are labeled to avoid (4). There are also “low potassium vegetables andfruits” listed with the implicit “warning” that large portions (more than half a cup) of even the “low”potassium foods may contain excess potassium. Given the repeated advice patients on dialysis hear to avoidpotassium-containing foods (as well as for years in predialysis CKD clinics), it is plausible that manypatients just chose to avoid fruits and vegetables to limit potassium. The inadvertent consequence of thisavoidance is that they fail to derive benefits from fruits and vegetables such as the antioxidants, fiber, andother benefits. Despite this recommendation, there is actually little data to support that eating fruits andvegetables increases serum potassium. A recent study in 140 patients undergoing dialysis showed nosignificant correlations between reported mean potassium intake and predialysis serum potassium level (4).Consistent with this, Saglimbene et al. (1) reports that predialysis potassium was not significantly differentacross tertiles of potassium intake. In our study of patients with CKD stage 4, we similarly did not see anincrease in serum potassium levels after switching to a 70% plant-based diet (5). Although hyperkalemia isindisputably an important health risk in those with CKD, it may be that avoiding fruits and vegetables isnot the best answer (4). Potassium intake and fruit/vegetable goals may need to be to individualized inthose on dialysis, taking into account that multifactorial nature of hyperkalemia, with muscle breakdown,systemic pH, insulin-mediated tissue distribution, and dialysis adequacy all playing a role.A recent set of semistructured interviews regarding diet in patients on dialysis shows that they believe thatdiets would improve their disease symptoms but that they are frustrated with confusing advice they receivewith respect to their diets (6). A word search of the term “diet” through each of the Kidney DiseaseImproving Global Outcomes (KDIGO) Guideline Statements reveals a few references. The KDIGO 2012Clinical Practice Guideline for the Evaluation and Management of CKD recommends “that individualswith CKD receive expert dietary advice and information in the context of an education program, tailored toseverity of CKD and the need to intervene on salt, phosphate, potassium, and protein intake whereindicated” (1B) as well as recommendations for level of protein intake (2C) and lowering salt intake (1C)(7), whereas the 2017 revised KDIGO CKD mineral bone disorder recommendations has a statement “toconsider phosphate source (e.g., animal, vegetable, additives) in making dietary recommendations” that isnot graded (8). The 2013 Lipid Guidelines discuss dietary changes to reduce serum triglycerides, with thecaveat that it is a weak recommendation, made on the basis of very low-quality evidence (9). In summary,patients on hemodialysis want dietary advice, but evidence regarding specific aspects of diets (includingfruit and vegetable intake) as well as a “unified” approach to prescribe eating patterns across nutrients inCKD stage 5D is currently lacking and, when available, extrapolated from the general population. Thismakes it difficult for clinicians to tailor dietary recommendations to patients on hemodialysis.How might the study by Saglimbene et al. (1) fit into the current literature for dietary management forpatients undergoing dialysis? In observational studies, larger magnitudes of effect sizes, a dose–responsegradient, and freedom from bias allow some upward rating of the quality of a study during a formalevidence review process (10). This study showed a 10% lower hazard of mortality with higher fruit andvegetable serving size from two to eight per week, and a 20% lower hazard ratio with 17 servings per week(compared with two per week), suggesting a dose–response gradient associated with the median number ofservings of fruits and vegetables and all-cause mortality. This dose–response relationship increases ourconfidence on the effect of fruit and vegetable intake in this study population. In this study, selection biaswas likely low, the primary outcome is a definitive clinical outcome (mortality), and exposure assessment(fruit and vegetable intake) is available in the majority of participants (83%). These are all strengths of thestudy. There are, however, limitations, the most important of which is that asking a question on food intakefor the previous year at a single point in time leads to significant potential for recall bias. The design of thestudy also limited the authors’ ability to adjust for some prognostic variables that could be responsible forDoes an Apple (or Many) Each Day, Keep Mortality Away? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390917/?report=printable2 of 4 4/13/2020, 2:48 PMresidual confounding, such as dialysis bath potassium, residual kidney function, seasonal variability in fruitand vegetable intake, and whether vegetables were eaten cooked or raw. The manner of cooking vegetablesmay affect level of dietary fat and advanced glycation end products and thereby outcomes (11). Theseunaccounted-for details in fruit and vegetable intake could explain the lack of relationship withcardiovascular mortality. However, these limitations do not minimize the importance of the study bySaglimbene et al. (1), as the impressive 20% reduction in all-cause mortality with higher fruit andvegetable intake will hopefully spur future studies by this group and others. The hope is this excellentcohort study will form the basis of well designed, randomized, controlled trials to test the effect of fruitsand vegetables in patients undergoing hemodialysis, so we, as their nephrologists, along with dieticians,can provide the details of dietary guidance they deserve.DisclosuresNone.AcknowledgmentsR.N.M. was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK102824-01A).FootnotesPublished online ahead of print. Publication date available at www.cjasn.org.See related article, “Fruit and Vegetable Intake and Mortality in Adults undergoing Maintenance Hemodialysis,” onpages 250–260.References1. Saglimbene VW, Germaine W, Ruospo M; Palmer S; Garcia-Larsen V, Natale P, Teixeira-Pinto A;Campbell K, Carrero J, Stenvinkel P, Gargano L, Murgo A, Johnson D, Tonelli M, Gelfman R, Celia E,Ecder T, Bernat A, Del Castillo D, Timofte D, Torok M, Bednarek-Skublewska A, Dulawa J, Stroumza P,Hoischen S, Hansis M, Fabricius E, Felaco P, Wollheim C, Hegbrant J, Craig J, Strippoli G: Fruit andvegetable intake and mortality in adults undergoing hemodialysis. Clin J Am Soc Nephrol 14: 250–260,20192. Miller V, Mente A, Dehghan M, Rangarajan S, Zhang X, Swaminathan S, Dagenais G, Gupta R, MohanV, Lear S, Bangdiwala SI, Schutte AE, Wentzel-Viljoen E, Avezum A, Altuntas Y, Yusoff K, Ismail N, PeerN, Chifamba J, Diaz R, Rahman O, Mohammadifard N, Lana F, Zatonska K, Wielgosz A, Yusufali A, IqbalR, Lopez-Jaramillo P, Khatib R, Rosengren A, Kutty VR, Li W, Liu J, Liu X, Yin L, Teo K, Anand S, YusufS; Prospective Urban Rural Epidemiology (PURE) Study Investigators : Fruit, vegetable, and legumeintake, and cardiovascular disease and deaths in 18 countries (PURE): A prospective cohort study. Lancet390: 2037–2049, 2017 [PubMed: 28864331]3. Health promotion and disease prevention knowledge gateway. The European Commission’s science andknowledge service, 2018. Available at: https://ec.europa.eu/jrc/en/health-knowledge-gateway/promotion-prevention/nutrition/fruit-vegetables. Accessed December 30, 20184. St-Jules DE, Goldfarb DS, Sevick MA: Nutrient non-equivalence: Does restricting high-potassium plantfoods help to prevent hyperkalemia in hemodialysis patients? J Ren Nutr 26: 282–287, 2016[PMCID: PMC5986180] [PubMed: 26975777]5. Moorthi RN, Armstrong CL, Janda K, Ponsler-Sipes K, Asplin JR, Moe SM: The effect of a dietDoes an Apple (or Many) Each Day, Keep Mortality Away? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390917/?report=printable3 of 4 4/13/2020, 2:48 PMcontaining 70% protein from plants on mineral metabolism and musculoskeletal health in chronic kidneydisease. Am J Nephrol 40: 582–591, 2014 [PMCID: PMC4374343] [PubMed: 25613675]6. Stevenson J, Tong A, Gutman T, Campbell KL, Craig JC, Brown MA, Lee VW: Experiences andperspectives of dietary management among patients on hemodialysis: An interview study. J Ren Nutr 28:411–421, 2018 [PubMed: 29691161]7. KDIGO CKD Work Group : KDIGO 2012 clinical practice guideline for the evaluation and managementof chronic kidney disease. Kidney Int Suppl 3: 1–150, 20138. Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, Moe SM, Shroff R, TonelliMA, Toussaint ND, Vervloet MG, Leonard MB: Executive summary of the 2017 KDIGO Chronic KidneyDisease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: What’s changed and why it matters.Kidney Int 92: 26–36, 2017 [PubMed: 28646995]9. Wanner C, Tonelli M; Kidney Disease: Improving Global Outcomes Lipid Guideline Development WorkGroup Members : KDIGO Clinical Practice Guideline for Lipid Management in CKD: Summary ofrecommendation statements and clinical approach to the patient. Kidney Int 85: 1303–1309, 2014[PubMed: 24552851]10. Guyatt GH, Oxman AD, Sultan S, Glasziou P, Akl EA, Alonso-Coello P, Atkins D, Kunz R, Brozek J,Montori V, Jaeschke R, Rind D, Dahm P, Meerpohl J, Vist G, Berliner E, Norris S, Falck-Ytter Y, MuradMH, Schünemann HJ; GRADE Working Group : GRADE guidelines: 9. Rating up the quality of evidence.J Clin Epidemiol 64: 1311–1316, 2011 [PubMed: 21802902]11. Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, Yong A, Striker GE, Vlassara H:Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am DietAssoc 110: 911–916.e12, 2010 [PMCID: PMC3704564] [PubMed: 20497781]Articles from Clinical Journal of the American Society of Nephrology : CJASN are provided here courtesy ofAmerican Society of NephrologyDoes an Apple (or Many) Each Day, Keep Mortality Away? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390917/?report=printable4 of 4 4/13/2020, 2:48 PM

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Does an Apple (or Many) Each Day, Keep Mortality Away?

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