COMMENTARY reasonable to consider P source Feasible Low-Phosphorus (e.g., animal, vegetable, additives) Dietary Patterns when making dietary recommen- dations (not graded, opinion). in Maintenance Because the level of evidence for Hemodialysis Patients: these interventions is still surpris- ingly disputed,2,4 firm dogmatic Need for Original Research conclusions do not yet seem possi- ble.S7 Furthermore, the optimal Jordi Bover1, Pablo Molina2, Pablo Ureña-Torres3,4 and María- target for serum P in CKD Dolores Arenas5 remains to be defined, and we 1 Department of Nephrology, Fundació Puigvert and Universitat Autònoma, IIB Sant Pau, now know that the priority REDinREN, Barcelona, Catalonia, Spain; 2Department of Nephrology, Hospital Universitari assigned to lowering serum P Dr Peset, FISABIO, University of Valencia, Valencia, Spain; 3Department of Dialysis, AURA should be individualized and may Nord Saint Ouen, University of Paris Descartes, Paris, France; 4Department of Renal Physiology, Necker Hospital, University of Paris Descartes, Paris, France; and 5Department differ depending on many factors.5 of Nephrology, Hospital del Mar and Pompeu Fabra University, IMIM, Barcelona, Catalonia, Nevertheless, all guidelines concur Spain that randomized clinical trials (RCTs) are needed to unequivo- Kidney Int Rep (2020) 5, 1845–1847; https://doi.org/10.1016/j.ekir.2020.09.008 cally demonstrate that treatments ª 2020 International Society of Nephrology. Published by Elsevier Inc. This is an open aimed at lowering serum P will access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ improve hard- or patient-centered by-nc-nd/4.0/). outcomes.4,S2–S4 See Clinical Research on Page 1945 A few short-term RCTs, some very old and relatively small, have evaluated the effect of lowering P utritional management has calcification, and aging—via both N classically been regarded as an integral part of therapy for chronic direct and indirect effects—is sup- ported by compelling epidemiologic intake or in combination with a low protein diet in CKD 3‒5D.S8–S11 Ac- cording to a recent Cochrane re- kidney disease (CKD).1,2,S1–S4 Various and experimental evidence, and view,6 there is limited interventional dietary constituents are consid- biologic plausibility.3,S5,S6 evidence that these dietary in- ered, 1,2 but, in the case of CKD‒ The 2017 Kidney Disease: terventions may positively affect mineral and bone disorders Improving Global Outcomes clinical CKD-MBD,6 and low certainty that (CKD-MBD), phosphorus (P) load practice guideline update for CKD- dietary modification makes any dif- and hyperphosphatemia have MBD4 suggested lowering elevated ference to clinical outcomes such as frequently been the focus of P levels “toward” the normal range quality of life, fractures, cardiovas- attention. Higher plasma P levels (Evidence 2C), and proposed that cular events, or mortality. Similarly, (even within the normal range) have decisions about P-lowering treat- in large observational cohorts, di- been associated with increased risk ment should be based on progres- etary intake or modification led to of incident CKD, vascular calcifica- sively or persistently elevated reduced urinary P excretion but did tion, and cardiovascular morbidity serum P (not graded). Importantly, not significantly change either and mortality.3 Moreover, the role of and in marked contrast to the level serum P or serum fibroblast growth P load and/or hyperphosphatemia in of evidence provided by the factor 23 (FGF23) levels, and it the pathophysiology of secondary recently published National Kidney remained unknown whether there hyperparathyroidism, renal osteo- Foundation (NKF) guidelines for were beneficial clinical oucom- dystrophy, left ventricular hyper- nutrition in CKD,2 the Kidney Dis- es.4,S12–S14 Somewhat surprisingly, trophy, accelerated progression ease: Improving Global Outcomes the recent NKF guidelines2 recom- of CKD, cardiovascular damage/ also suggested limiting dietary mend (Evidence 1B) adjusting di- P intake in the treatment of etary P intake to maintain serum P hyperphosphatemia alone or in in the normal range in adults with Correspondence: Jordi Bover, Department combination with other treatments CKD 3‒5D. Thus, there is a of Nephrology, Fundació Puigvert, C. Cartagena 340-350, 08025 Barcelona, (Evidence 2D). Moreover, in both remarkable disparity in evidence Spain. E-mail: jbover@fundacio-puigvert.es guidelines it was considered level (Evidence 1B vs 2D) compared Kidney International Reports (2020) 5, 1845–1847 1845 COMMENTARY J Bover et al.: Dietary Patterns in CKD with the Kidney Disease: Improving that some of the changes would absorption, increased magnesium Global Outcomes guidelines,2,4 but have increased total P intake. and vitamin K, and even the latter nevertheless still consider However, beyond offering helpful improvement in gut dysbiosis and dietary P restriction to be an methodologic contributions rele- reductions in inflammation and important standard of practice to vant to the design of future RCTs, oxidative stress, have been lower elevated P levels, as several this pragmatic study underlines observed with vegetarian diets lines of evidence suggest that this the possibility of a significantly (and adequate cooking tech- strategy may be effective at least in wider food choice (even including niques).S24 In their study,8 the hyperphosphatemic advanced CKD or previously “prohibited” products), authors somewhat altered their maintenance hemodialysis (MHD) without a resultant increase in P or standard renal diet toward a patients.4,7 For this reason, a “cease- K levels in an era when patient- locally adapted Mediterranean di- fire” in the war on dietary P has centered approaches to treatments etary pattern, retaining the ability been considered premature,7 and the must be considered. This greater to individualize nutrient re- need for RCTs to address the effects choice may also improve adher- strictions without affecting serum of various dietary interventions for ence.S15 Moreover, the modified K. Considering that, on a global patients with CKD-MBD has been diet provides the advantages and scale, there are quite significant emphasized.4,7 potential pleiotropic beneficial ef- differences in diet compositions In this issue of the journal, fects of an effective higher dietary and food availability, such pattern Byrne et al.8 analyze, in a pilot fiber intake (a significant increase modifications seem of great inter- RCT, the short-term (1-month) ef- in bowel movements was est. Similarly, some modifications ficacy, safety, and tolerability of an reported).S16 have recently been made to the Irish national standard versus As the authors point out, New Nordic diet in order to modified low-P diet in 74 MHD nutrition science is moving toward decrease its P content and absorp- adults, with an average serum P of dietary patterns instead of indi- tion, although these have been >5 mg/dl over the last 3 months vidual food nutrients.S17–S21 In tested for only 1 week in non- (mean baseline of 5.92 and 6.13 particular, the Mediterranean, dialysis CKD patients.9 mg/dl, respectively). Of note, New Nordic, and the Dietary Ap- Another important piece of in- because of the pragmatic nature of proaches to Stop Hypertension di- formation provided is the infre- the study, fasting and nonfasting ets have shown beneficial effects in quently reported phytate-bound P blood samples were collected, preventing and managing renal (significantly higher in the modi- likely influencing these P levels disease, at least in selected fied diet). Thus, dietary P sources and masking the basal effect of the adherent individuals.S18–S21 Both were divided into foods with P standard low P diet. The standard the Mediterranean and the Dietary that is or is not bound to phytate. diet restricted pulses, nuts, whole Approaches to Stop Hypertension Estimates of dietary P from food grains, and other high P foods, diets overlap in nutritional composition tables likely underes- whereas the modified diet replaced composition, encouraging whole timate the P content because they some meat with plant-based vege- foods such as fruits, vegetables, mostly reflect the “natural” P tarian proteins and unsalted pea- pulses, whole grains, and nuts.S17 content of foods, but composition nuts, increased the use of whole- In addition, these diets restrict and absorption may differ accord- grain breads and cereals, included animal protein consumption and ing to food processing. Moreover, egg whites (very low ratio of P/ limit processed and fast foods.S17 especially in patients lacking kid- protein), and had an increased However, in later CKD stages and ney function, it is very important focus on the avoidance of P in patients on MHD, the pre- to consider the bioavailability of P additives. scribed dietary pattern needs to be based on its sources (organic vs. At first glance, the results of more carefully individualized for inorganic).S25 Nephrologists this small study may seem some- specific nutrients (i.e., P, K, and/or should be aware of the almost what disappointing with regard to protein content). For instance, 100% bioavailability of inorganic the primary goal of reducing P traditional dietary CKD recom- P (such as in additives) and the and/or FGF23 levels. The non‒ mendations limit the intake of reduced bioavailability of organic statistically significant small de- fruits and vegetables because of P in plant foods due to the limited creases in serum P ( 0.336 their high K content. Nevertheless, absorption of phytate-based P in and 0.295, respectively) may be this paradigm is rapidly chang- the human gastrointestinal tract attributable to not only high indi- ing.S22–S24 A higher fiber content, (owing to the lack of the enzyme vidual variability but also the fact acidosis neutralization, decreased P phytase, necessary to degrade 1846 Kidney International Reports (2020) 5, 1845–1847 J Bover et al.: Dietary Patterns in CKD COMMENTARY dietary phytate and release P).S25 upcoming studies it would be most acknowledges advisory and/or lec- Therefore, many of the foods helpful to closely follow up body ture fees from Amgen, Sanofi- traditionally labeled as containing composition and other nutritional Genzyme, Shire, and Vifor-Frese- high amounts of P (e.g., beans and parameters.2 Hopefully, these di- nius-Pharma. nuts) may be acceptable as protein etary regimens will be used, at sources in view of their low ab- least in selected MHD patients, SUPPLEMENTARY sorption rate (K permitting). The over long periods, and it must be MATERIAL potential importance of considering demonstrated that the prescribed Supplementary File (PDF) phytate-bound P is stressed by our diet is sustainably tailored to pa- Supplementary References. recent study demonstrating that an tients’ needs and habits. Finally, it intravenous formulation of phytate remains to be proven whether the REFERENCES (SNF472) significantly attenuated addition of P- or K-binders may 1. Kalantar Zadeh K, Fouque D. Nutritional the progression of coronary artery improve results without signifi- management of chronic kidney disease. and aortic valve calcification in cantly interacting with other N Engl J Med. 2017;377:1765‒1776. MHD patients.S26 Dietary regimens drugs, the absorption of other nu- 2. Ikizler TA, Burrowes JD, Byham- prescribed for MHD patients trients, or the intestinal Gray LD, et al. KDOQI Clinical practice reduce the intake of many of the flora.S24,S28,S29 guideline for nutrition in CKD: 2020 main phytate-containing foods.S27 Although the differing ap- update. Am J Kidney Dis. 2020;76(Suppl. 1):S1‒S107. In experimental and some human proaches and opinions of medical studies (mostly observational), societies and national guidelines2,4 3. Covic A, Vervloet V, Massy ZA, et al. Bone and mineral disorders in chronic phytate has been associated with are puzzling, the need to under- kidney disease: implications for car- several beneficial properties.S27 take challenging RCTs is always diovascular health and ageing in the Beyond the many strengths and acknowledged. In this context, we general population. Lancet Diabetes certain weaknesses of the study welcome any information, such as Endocrinol. 2018;6:319‒331. (i.e., short-term, heterogeneity of P that derived from this pilot RCT, 4. 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Although the apparent comes, or at least patient-related terventions for mineral and bone dis- reduced protein intake may be due outcomes. order in people with chronic kidney disease. Cochrane Database Syst Rev. to underreporting, and is unlikely 2015;9:CD010350. to be of a different magnitude when comparing both arms, it may DISCLOSURE 7. Evenepoel P, Vervloet MG. Dietary phosphorus restriction in predialysis represent a safety signal that JB acknowledges advisory and/or chronic kidney disease: time for a should be closely followed. In fact, lecture fees from Amgen, Abbvie, cease-fire? Kidney Int. 2016;89:21‒23. there is general agreement that, Sanofi-Genzyme, Shire, Vifor- 8. Byrne FN, Gillman BA, Kiely M, et al. when targeting dietary P restric- Fresenius-Pharma, and Sanifit. PM Pilot randomized controlled trial of a tion for MHD patients, the focus acknowledges consultation or standard versus a modified low-phos- should clearly be on P additives speaker honoraria from Abbott phorus diet in hemodialysis patients. Kidney Int Rep. 2020;5:1945–1955. and not protein.7 Therefore, Nutrition, Amgen, Nutricia, Palex, although the authors describe no and ViforPharma. PU-T acknowl- 9. Salomo L, Rix M, Kamper A-L, Thomassen JQ, Sloth JJ, Astrup A. Short- significant differences in protein edges advisory, lecture fees, and/or term effect of the New Nordic Renal Diet intakes, weight, predialysis travel funding from Abbvie, Amgen, on phosphorus homoeostasis in chronic urea, or baseline urea reduction Astellas, Medici, Sanofi, Vifor- kidney disease stages 3 and 4. Nephrol ratio between the 2 groups, in Pharma FMC, and Hémotech. M-DA Dial Transplant. 2018;34:1691–1699. Kidney International Reports (2020) 5, 1845–1847 1847