Skip to main content

Low protein diets in patients with chronic kidney disease: a bridge between mainstream and complementary-alternative medicines?

Abstract

Dietary therapy represents an important tool in the management of chronic kidney disease (CKD), mainly through a balanced reduction of protein intake aimed at giving the remnant nephrons in damaged kidneys a “functional rest”. While dialysis, transplantation, and pharmacological therapies are usually seen as “high tech” medicine, non pharmacological interventions, including diets, are frequently considered lifestyle-complementary treatments. Diet is one of the oldest CKD treatments, and it is usually considered a part of “mainstream” management. In this narrative review we discuss how the lessons of complementary alternative medicines (CAMs) can be useful for the implementation and study of low-protein diets in CKD. While high tech medicine is mainly prescriptive, prescribing a “good” life-style change is usually not enough and comprehensive counselling is required; the empathic educational approach, on which CAMs are mainly, though not exclusively based, may support a successful personalized nutritional intervention.

There is no gold-standard, low-protein diet for all CKD patients: from among a relatively vast choice, the best compliance is probably obtained by personalization. This approach interferes with the traditional RCT-based analyses which are grounded upon an assumption of equal preference of treatments (ideally blinded). Whole system approaches and narrative medicine, that are widely used in the study of CAMs, may offer ways to integrate EBM and personalised medicine in the search for innovative solutions respecting individualization, but gaining sound data, such as with partially-randomised patient preference trials.

Peer Review reports

Background

Chronic kidney disease (CKD): an example of a highly complex, life-long disease

Dialysis and transplantation are life-long, life-sustaining treatments requiring multiple drug therapies, and a high technological level of “mainstream medicine” [13]. However, like all life-long, chronic diseases they require not only integration of complex therapies into everyday life (multiple drugs in the earlier phases of the diseases, and then drugs and dialysis or drugs and a kidney transplant, not necessarily in this order), but also a change in lifestyle, including diet.

In this regard, CKD treatments merge technology (dialysis, transplantation, multiple drug therapy), which belongs to/“mainstream medicine”, and lifestyle interventions (exercise, weight loss, low-protein diets) which are conversely often considered a part of the holistic approach attributed to “complementary and alternative medicine” (CAM).

While several comprehensive reviews have addressed the issue of the efficacy of various therapeutic approaches, including diet, to date, no reviews have been dedicated to the relationship between a mainstream and a CAM approach to low protein diets in CKD patients.

Indeed, nutritional treatments share these two facets: several recent papers aimed at a vast readership of family practitioners which assessed diverse diseases cite the addition of different foods or the use of specific diets as part of CAM approaches [47].

For at least a century chronic uraemia has been considered an example of “protein intoxication”. Thus, in the history of “renal medicine”, diets have been attempted as a way to correct the metabolic alterations of kidney failure as much as possible [8, 9]. Indeed, the first systematic studies on low-protein diets in uraemia patients started with the observation that a protein-restricted diet was effective in reducing the symptoms of “uraemic toxicity” and that it was even able to prolong life [1012]. This role of life-prolonging therapies was maintained in western countries until dialysis became widely available; availability of dialysis, no more a problem in Europe, is however non universal on a global scale [1221]. Reconsidering the goals and modalities of low-protein diets in progressive renal diseases and keeping in mind the lessons of CAMs may offer an interesting outlook in the context of “high-tech” CKD care [20, 2224]. At a time in which growing interest (and business) in CAMs may divert attention from high-tech medicine, “playing in the two fields” may also aid the physicians in helping patients find effective coping strategies.

Chronic kidney disease in the new millennium: why is it difficult to measure progression?

At the beginning of the new millennium, “renal insufficiency” was redefined and CKD became an umbrella term encompassing several affections having variable evolution rates towards end-stage kidney disease (ESRD) [2527]. The staging of CKD underlines the similarities of all advanced kidney diseases, despite different progression rates which depend upon race, age and underlying nephropathy [2535].

Therapies aimed at slowing CKD progression have to deal with high baseline heterogeneity that hinders the demonstration of their long-term advantages and drawbacks [3036]. Even the method that is used to measure progression rate is a matter of controversy. Furthermore, differences in the hard outcomes, namely start of dialysis or death, require trials with long observation times which are expensive and are often affected by many confounding factors [2836].

Several studies have focused on different therapeutic goals which may partially overlap: these goals include removing the cause of CKD, treating the metabolic derangements, correcting lifestyle habits that are not necessarily consequent to CKD but that may potentially worsen the diseases, and reducing the work-load on the remnant nephrons [20, 37, 38].

Dietary interventions in general, and low protein diets in particular may play a role at all these levels by, for example, treating obesity, correcting hypophosphataemia, avoiding processed foods, and most importantly, reducing the work-load on the remnant nephrons.

Furthermore, the outcome measure is non-univocal: slowing the progression of CKD is not synonymous of delaying dialysis [20].

Long-term follow-up of either homogeneous populations with similar baseline progression rates or of very large cohorts is ideally needed to demonstrate an effect of dietary interventions (and, indeed, one of the observations of the famous MDRD study was that it would have probably given different results over a longer follow-up [3941]). The initial GFR decrease, achieved by “renal rest”, or correction of the relative hyperfiltration may interfere with short-term analyses [42, 43].

Conversely, delaying dialysis requires attaining stable metabolic balance that is, at least partly, independent of GFR. However, the analysis of this short term goal is only apparently easier since it is deeply entangled with the pharmacological “mainstream approach” and reflects various policies of dialysis start which are not merely based upon (relatively) simple measures, such as GFR. The new Canadian guidelines on dialysis start clearly underline that whenever an “intent to defer” policy is chosen, wise clinical judgement cannot be replaced by formulae [44].

Heterogeneity of diseases, heterogeneity of progression, and heterogeneity of goals and measures add to the charm, but also to the complexity of the analysis of dietary approaches in CKD patients. Without a change in the approach, the issue will probably remain open forever.

Low-protein diets in CKD: why is the evidence not evident enough?

Many of the questions posed in the 1986 paper published in the Lancet entitled: “Dietary treatment for chronic renal failure, ten unanswered questions” are currently still unanswered. Among them, some highlight the complexity and heterogeneity of chronic kidney disease (Does chronic renal failure always progress?), while others underline the difficulties in standardization of low protein diets in clinical practice (When should a low-protein diet start? Which low-protein diet? How should we assess progression, nutritional status or compliance?) [45]. However, in the literature there are several evidence-based demonstrations of the possible role low protein diets may play in delaying ESRD, including several RCTs and a Cochrane review [4658]. Furthermore, we are not aware of any large studies demonstrating a higher progression rate in non-malnourished, on-diet patients; in addition, data on lower costs are concordant [48, 49, 51], and there is no evidence showing that being on the diet results in any survival disadvantage after the start of dialysis [51, 59, 60].

The risk of malnutrition is frequently cited, but the data are at best as inconclusive as those cited by the diet “advocates” [6168].

Low protein diets are however still underutilized [20].

Table 1 summarizes some of the reasons why even “best quality” evidence is often considered non conclusive or does not affect the clinical management of CKD patients. Many of these reasons underline how the prescriptive modality, which is typical of high-tech medicine, may be less suitable than the educational modality, which is typical of CAMs, for the management of diets in CKD patients.

Table 1 Some comments on the main RCTs con LPDs enrolling at least 50 patients per arm

The first reason why the treatment with the best cost-benefit ratio is underutilized in the expensive CKD scenario may be the difference between the amount of time it takes to prescribe a drug or define the parameters of a dialysis treatment (mainly requiring technical skills), and to recommend lifestyle changes (especially in the case of diet) which are deeply rooted in personal preferences and social habits. In this regard, the barriers for the implementation of LPDs may be the result of the difficulty in conciliating the prescription and follow-up of a diet with a classic “mainstream medicine” approach. Some comments regarding the MDRD study, the largest randomised controlled study on LPDs in CKD, are in line with this interpretation: some experts claimed that MDRD actually demonstrated that prescribing a diet is not enough, since patients tend to lean to the dietary habits of their choice [3943]. Hence, the results of the “intention to treat” analysis (diet as a “mainstream prescription”) are negative (no advantage of an LPD on CKD progression), while the results of the “per protocol” analysis (diet as an educational intervention) suggest a positive role for LPDs in slowing CKD progression (Table 1).

The outstanding results obtained in some centres with a great deal of experience in selecting and following-up patients on low protein diets have rarely been replicated in other settings [5159]. The selection issue is fundamental: randomization is felt to be unethical on dialysis: this is why peritoneal dialysis and hemodialysis have never been randomised and their results are acknowledged as a matter of prescription and therapeutic adherence. Strangely enough, the same caveats are not applied to diets. Diet, as well as dialysis, depends upon the patients’ choices, and the few RCTs that were performed on dialysis frequency (3 versus 6 dialysis sessions per week) and those carried out on very low protein diets share an extremely low enrolment rate (in the 10–30 % range) [5254, 59, 6971]. Accordingly, one of the main criticisms of the unique Brunori study on diet versus dialysis is that it enrols about 30 % of the population screened for recruitment (and the percentage of cases randomised in the Garneata trial on very low protein diets is about 10 %) (Table 1). Such a low prevalence demonstrates the presence of a strong patient preference and suggests that adapting the prescription to the individual may be more successful than randomizing therapies. These issues merge with those related to quality of life, as will be further discussed [7277].

Diet is not a drug: the “low-protein menu” in CKD

Wikipedia, the world’s largest source of on-line information, states “diet is the sum of food consumed by a person or other organism”; however, in clinical practice, the word “diet” is often interpreted with a restrictive (or even punitive) connotation, meaning the reduction of at least some foods [77, 78]. Limiting, reducing, and abolishing, are probably not the best slogans for a “marketing strategy” to improve compliance among CKD patients. Indeed, some authors presently prefer the terms “nutritional treatments” or “nutritional interventions” to define strategies aimed at changing dietary habits and not at restricting the use of some (many-most) foods [7780].

The concept of low-protein diets is presently undergoing a substantial change, mainly as a consequence of the changes in the definition of “adequate” protein intake which has shifted in recent years from 1–1.2 g/Kg/day to 0.8 g/Kg/day, according to the most recent FDA Reference Daily Intake or Recommended Daily Intake [81, 82]. The issue of dietary protein content in the overall population is complex, and is entangled with that of healthy lifestyle; the rediscovery of traditional and Mediterranean diets, and the attention to reducing additives and processed foods are two emerging aspects of this issue [8390].

A low protein diet is not necessarily a healthy diet; however, the cultural trend towards reducing proteins and canned, preserved and processed foods plays in favour of our patients, for whom the older “moderate” protein restriction (0.8 g/Kg/day) is now synonymous of a “biologically normal/adequate” protein intake, and who may choose a vegan-vegetarian or traditional diet (for example “Mediterranean”) with a lower risk of being “discriminated” in a carnivorous world [77].

Table 2 shows the main “menus” of low protein diets as defined according to; the daily protein intake relative to body weight, to the main foods, to the room for personalization and to the type of approach (“mainstream prescription” versus “CAM education”).

Table 2 The “LPD menu”: some reflections on compliance

Vegan-vegetarian diets

In the general population, veganism and vegetarianism are not only diets, they are integrated into a philosophy of life. This is a setting in which a mainstream approach (need to reduce proteins) finds a fertile ground in the growing attention to a “healthy” lifestyle and in a philosophy of life which ranges from respect for animals to avoiding diseases [9195]. Hence, such diets are often listed along with CAMs in the treatment of diseases other than CKD. Overall, the protein content in vegan diets is lower than in omnivorous diets, and it is roughly 0.7 g/Kg/day. However, they are usually considered together with the “0.6” omnivorous diets on account of the lower absorption and bioavailability of vegetable proteins and of their lower effect on renal filtration [96105].

Vegan-vegetarian diets are often discussed together since the distinction between them is relatively new. The term vegan was coined in 1944 by Donald Watson: “vegan” from the beginning and end of vegetarian “because veganism starts with vegetarianism and carries it through to its logical conclusion”. The two definitions were often used interchangeably in the past, however, these diets are different: vegan diets avoid any foods derived from an animal source, including eggs and dairy products [9195]. The list of variants is long and includes various combinations such as ovo-vegetarian (eggs only), lacto-vegetarian (milk and dairy products), pescetarian or pesco-vegetarian (fish is allowed). As for vegan diets, honey is excluded by some, and allowed by others and the same is true for shellfish. In a world of processed food, vegans-vegetarians try to avoid all animal-derived components, such as sugars that are whitened with bone char, cheeses that use animal rennet, or gelatine from collagen. The attitude of “no harm” is extreme in fruitarianism, which is based upon fruit, nuts, seeds, and food gathered without “harming the plant” [94, 95, 106].

It is thus clear that, beyond the CKD context, the differences are not related to “food” but also to the “concept of food” and, more extensively, to the concept of life [9195].

It is worth remembering a paper which signalled a new interest in LPDs in CKD patients which appeared about 30 years ago in the BMJ. It dealt with CKD in a group of Buddhist monks as compared with other subsets of Indian CKD patients. The very low protein content was indicated, together with the practice of meditation, as the putative cause of the very low progression rate in the monk population; at that time, the fact that Buddhist monks are vegetarians was not mentioned [107, 108]. Collaterally, we may also cite that prayer and meditation are presently considered the most widespread CAM worldwide [109, 110].

Regardless of the reason for making this choice, be it medical of personal, the preparation of vegan food is time consuming and attention must be paid to integrating different types of cereals, nuts and legumes into each meal to avoid nutritional deficits; however, provided deficits are avoided, these diets are safe in all phases of life, including pregnancy and lactation [111114].

Supplemented vegan diets

Vegan-vegetarian diets are the basis for further integration into different schemes: very low protein (or “0.3”) diets are basically vegan and are supplemented by protein-free foods to supply energy, and by a mixture of aminoacids and ketoacids; a “0.6” simplified scheme has also been developed, with promising results also in elderly, diabetic or pregnant CKD patients [115124]. Supplements are however “pills”; they may have an additive effect as scavengers of uraemic toxins, but they have to be prescribed, hence the educational and prescriptive approaches are combined. While different combinations of aminoacids and ketoacids were used in the past, in Europe two are available and are marketed by the same Company, the difference being the absence of tryptophan in the preparation that is available in Italy. The dose of the supplements is standardized in the “0.3” diet (1 pill every 5 Kg of body weight), while in the 0.6 diets a “compromise dose (1 pill/10 Kg) is chosen in an effort to find a balance between “too many pills” and the risk of malnutrition which is intrinsically linked to CKD and is enhanced by acidosis, depression, and possibly even by unbalanced diets [116, 125].

The role of supplements is different in “very low” and “low” protein diets: in the former they are needed to avoid protein malnutrition while in the latter, the addition of supplements allows to simplify the dietary scheme in previously omnivorous patients who are “forced” into a vegan regimen, or in patients who do not like protein-rich plant foods, namely legumes.

Omnivorous traditional diets

Hippocrates said that food is the first medicine.

Humankind has quickly shifted in the last century from relatively low food availability to a higher protein and energy supply. In many traditional diets, including Mediterranean diets or the extensively studied Okinawa diet (from one of the islands with the greatest longevity in the world), animal-derived food is a sort of “nutritional complement” on the basis of an otherwise vegan diet [126134]. As a consequence, moderate protein restriction may be feasible in the context of several “traditional diets”. This issue is coming of age in a moment in which attention is being placed on healthy food and on consuming food that is processed minimally or not at all, which is possible only if it is produced in the surrounding area (i.e., “zero Km” food), thus implicitly supporting a return to a more traditional cuisine.

Adaptation may be difficult in settings where the baseline diet is poor in vegetables, fruits, cereals and legumes; however it should be kept in mind that animal-derived protein content has only recently risen in the “rich” world and that most traditional or “poor” cuisines have a relatively low protein intake [134137]. Taking into account that CKD is mainly a disease of the elderly and that the sharp increase in protein intake occurred in most of the western world less than one century ago, designing tailored traditional diets in CKD may follow an “historical” educational approach in which patients are solicited to go back to their childhood to find adequate or adaptable dietary patterns.

0.6- diets with protein-free food

Protein-free food is an idea that was “made in Italy” and conceived in an era of limited dialysis availability: “protein-free pasta” was invented in the sixties in a search for calorie-rich, protein-poor food [138].

In fact, other natural protein-free, energy-rich foods (tapioca, butter, sugar, fruits, vegetables) could be combined only in very monotonous diets which were extremely difficult to follow especially by patients who were already experiencing the deleterious effects of uraemia and acidosis on both their appetite and on gastrointestinal motility. The systematic use of protein-free food is limited to Italy where these products are available free of charge to CKD patients and where up to half of the protein intake derives from bread and pasta (12 g of protein per 100 g). Replacing these foods allows patients to reach the target protein intake without making any substantial changes in dietary habits [138141]. In Italy, these diets are often well followed by elderly patients while, at least in our experience, younger patients prefer vegan approaches [142145]. A prescription approach focused on consuming bread and pasta “from the pharmacy” is usually enough. Since however they are less palatable than what people are used to, education, aimed at understanding the reasons and goals of the LPD and at suggesting specific ways of cooking food to improve taste, represents an important strategy for improving adherence and coping.

Mainstream, complementary medicine and CKD: where is the diet?

On Google, the term “mainstream medicine” retrieves over 3 million results and there are several different definitions among the first hits. Some of them are tautological and some are centred on “who” practices the medicine: “Medicine as practised by holders of M.D. or D.O. degrees and by their allied health professionals” [146]. Other definitions focus on the type of treatment “A system in which medical doctors and other healthcare professionals (…) treat symptoms and diseases using drugs, radiation, or surgery” [147]. Others are more complex and include an explanation of the pathogenesis of the diseases: a general term for conventional healthcare based on the “western model” of evidence-based practice for diagnosing and treating disease. Mainstream medicine assumes that all physiologic and pathological phenomena can be explained in concrete terms, and “best practice” is the final result of a stream of objective analyses. They begin with non-human model systems, evolve through blinded studies and a statistical analysis of the results, finally leading to guidelines to which doctors should adhere in order to achieve optimal patient outcomes [148]. In addition, they also include social elements: “The approach to healthcare as practised in developed nations is based on scientific data for diagnosing and treating disease; mainstream medicine assumes that all physiologic and pathological phenomena can be explained in concrete terms; the tools of mainstream medicine include non-human model systems, blinded studies, and statistical analysis to ensure reproducible results” [149].

Diet or nutritional approaches are never cited within these definitions of mainstream medicine. Conversely, on Medline plus, along with a general definition of Complementary and alternative medicines, CAM is the term for medical products and practices that are not part of standard care. Standard care is what medical doctors, doctors of osteopathy, and allied health professionals, such as nurses and physical therapists, practice. Dietary supplements are cited, while natural products are in first place in the classification of CAMs in the National Institute of health website [150, 151].

Diet prescription in mainstream medicine and CAMs

The concept of diet may however be different in mainstream and complementary medicine: in the first case, it is usually based upon specific, measurable prescriptions, while in the second case it is more commonly part of a lifestyle, often with emphasis on disease prevention [7]. The limits are elusive, and no wonder, therefore, if a broad search strategy on Medline, combining the terms “Chronic kidney disease” and “alternative” or “complementary” or “allied” medicine retrieves, along with papers on CAMs, several studies on diets which are often defined as “alternative” to early dialysis, or “complementary” to pharmacological treatments. Thus, even if diet in CKD is not strictly considered a CAM, the terms currently employed for defining CAMs (complementary or alternative) identify many relevant recent papers on the dietary treatment of CKD [152157].

The use of these terms is probably not only a semantic exercise: diet is often cited as an alternative to early dialysis or as a treatment that is complementary to ACE-inhibition or to other drug therapy (for instance, diuretics) [20, 158161]. In this regard, a critical observation from the CAM point of view may offer some insights for a better understanding of the limits of applying “conventional” evidence-based medicine (EBM) analysis to low-protein diets in CKD, as well as into the possible role for a “whole system” analysis and for a narrative, personalized approach to maximize compliance (or, perhaps better stated as “concordance”) to low-protein diets in CKD patients [162165].

Personalised medicine, or RCTs? The lesson of the holistic, whole system approach

In the era of personalised medicine, we might wonder whether a randomised controlled trial is the best way to demonstrate the effects of changes in dietary habits and, more than this, if it is ethically sound to randomise such an intrusive lifestyle change [166169].

In this regard, mainstream medicine should reflect on the lesson learned from CAMs and the focus might shift from proving the superiority of a single treatment (diet vs no diet; moderately- versus severely-restricted diets etc.) to an observational multidimensional “whole system” approach [7, 170177].

A very interesting health technology assessment on the role of the preferences of professionals and patients in randomised controlled trials states that “All RCTs in which participants and/or professionals cannot be masked to treatment arms should attempt to estimate the participants’ preferences….” [178]). Current approaches may not be fit to highlight differences, and other study designs, in particular the new “partially randomized patient preference (PRPP) trial model”, which was developed for the analysis of CAMs, have already been applied to several fields of mainstream medicine [179186].

No study is without pitfalls, and there are sound criticisms to virtually every study design [187]. However, according to an educational report in the BMJ: “when the effectiveness of the intervention depends on the subject’s active participation (…) a randomised trial may be inappropriate because the very act of random allocation may reduce the effectiveness of the intervention” [173].

If the focus on diets has to shift from issues regarding effectiveness to those of feasibility, then the implementation strategy should probably be personalized and should take into account the features of each patient [142]. This “narrative” approach may be seen as the other side of the moon as compared to a randomised trial approach. However, evidence-based medicine is fully compatible with narrative, individualized approaches provided that flexible, comprehensive and innovative study designs are chosen [188190]. Paraphrasing a JAMA paper “Scientific reports (or RCTs) are genuinely dispassionate, characterless, and ahistorical. But their translation and dissemination (implementation in clinical practice) should not be” [191]. Dealing with personalized medicine, we should probably learn from patients’ preferences, and be happy with the fact that a treatment may have positive results, at least in experienced centres, in the absence of sound evidence on severe drawbacks and side effects. In this regard, the lessons learned from dialysis, which is chosen on the basis of the patients’ preference in the setting of an overall equivalence of side effects, may be extended to the diet, which is probably wrongly considered less intrusive in daily life than the choice of the different types of renal replacement therapy [6971].

What we did not discuss, but should not forget

Talking about diet, broadly defined on Wikipedia as “everything we eat”, is extremely complex and no review of a single issue, such as protein intake, can be exhaustive without touching upon other aspects, such as caloric intake, vitamins and oligo-elements, additives and contaminants. In particular, this is crucial in CKD where the presence of kidney disease impairs the activation of vitamin D, leading to a deficient absorption of calcium and to hyperphosphataemia; low-protein diets are usually deficient in vitamin B12, vitamin D, and iron. Conversely, hyper-vitaminosis may be a threat, in particular for vitamin D [192194]. The toxicity of additive and trace elements, such as pesticides, has only recently been studied; negative effects are likely to be enhanced by reduced renal depuration [194196]. We know less about individual elements, such as selenium, which is important in the oxidative pathway; furthermore, the network of saturated-unsaturated fatty acids is extremely complex and only partly known, and bicarbonate supplementation is still an open issue, while the discussion on all these items is beyond the scope of this review [197199]. Again, a flexible holistic approach, which is more common in CAMs than in mainstream medicine, may be of interest. Allowing at least one (and in our experience up to three) free meals per week may help avoid deficits, generically speaking by enriching the diet, but the idea that “body wisdom” can help identify which foods the body needs is appealing [24, 200]. A holistic approach not only to the patient, whose diet is an important part of daily life, but also to the diet as a whole and not only as a “reduction of” may reduce the risk of focusing on single elements, and thus losing sight of the whole problem.

Tips for counselling

There is probably at present no best low-protein diet, but, in the absence of contraindications, the best approach is probably to offer the patients a choice of diets with different options and protein content, bearing in mind that the most important issue is not the optimal prescription, but the optimal compliance and target achievement (Table 2).

In this regard, the prescriptive approach that deals with low protein diets as it does with drug therapies may be combined with the educational approach that is typical of CAMs by integrating dietary habits into daily life [201203].

Patients should be aware that there is a high degree of uncertainty with regard to the choice of their dietary treatment and that its aim is to reduce the signs, symptoms and complications of renal failure and then to delay the need for dialysis. Furthermore, even if this is beyond the scope of this review, they should be warned that a low-protein diet is not necessarily a healthy diet, and that several other factors, such as type of renal disease, type of proteins, salt and phosphate intake, use of canned and processed food, and effective energy intake can modulate the risks and the clinical success [194196].

Suggestions for research

Long-term interventions that require a profound change in everyday life are difficult to assess, at least with the current study strategies. Clinical research needs long-term observations and long term follow-up, whenever possible even after the start of dialysis, to check for carry-over effects and for attrition biases. Since the report and publication biases suggest that only experienced centres with sound, positive data should publish their series and studies, efforts should be made to build large multi-centre series involving centres with different types of experience on low-protein diets. Multi-centre studies should take into account the important cultural differences in eating habits and cuisine which are often present even within the same country. Both “per protocol” and “intention to treat” analyses may be relevant in chronic interventions and both should probably be analysed [203, 204].

Since it is somewhere between a mainstream prescription and a complementary therapy, the study of diet in chronic kidney disease should merge the suggestions of both approaches. Integration among various study designs that take into account patients’ preferences (observational, randomised, partially randomised, etc.) is more promising than focussing on a single type of analysis, be it randomised or observational.

Conclusions

There is no ideal low-protein diet for all CKD patients.

However, on the basis of the present evidence which shows an advantage in terms of dialysis-free follow-up, and a lack of advantage (or even a disadvantage) in early dialysis start, all CKD patients should be offered a “good diet”, or better, an option among various “good diets” since the best one is the one that is truly followed by the patient. The methodological flaws and limitations of the present evidence are probably also linked to the fact that “traditional” RCTs are based upon an assumption of equal preferences that is not applicable to low-protein diets.

A diet is not a drug.

Diet integration into daily life is highly dependent upon preferences and personal choices, and in this regard, the experience of CAMs may be important for integrating this potentially precious tool into the life of our patients, shifting our efforts from standardization to adaptation, as per the lesson of narrative medicine.

These approaches do not clash with classic, evidence-based medicine; on the contrary, they need solid EBM support, integrating the conventional, more rigid study designs, such as RCTs, with new ones, such as whole-systems approaches or partially randomised patient preference trials.

References

  1. Eknoyan G. Artificial kidneys: progress and promise. Lancet. 2007;370:1977–8.

    Article  PubMed  Google Scholar 

  2. Sinnakirouchenan R, Holley JL. Peritoneal dialysis versus hemodialysis: risks, benefits, and access issues. Adv Chronic Kidney Dis. 2011;18:428–32.

    Article  PubMed  Google Scholar 

  3. Remuzzi G, Benigni A, Finkelstein FO, et al. Kidney failure: aims for the next 10 years and barriers to success. Lancet. 2013;3(82):353–62.

    Article  Google Scholar 

  4. Zoorob R, Chakrabarty S, O’Hara H, Kihlberg C. Which CAM modalities are worth considering? J Fam Pract. 2014;63:585–90.

    PubMed  PubMed Central  Google Scholar 

  5. Snyder J, Brown P. Complementary and alternative medicine in children: an analysis of the recent literature. Curr Opin Pediatr. 2012;24:539–46.

    Article  CAS  PubMed  Google Scholar 

  6. Huebner J, Marienfeld S, Abbenhardt C, et al. Counseling patients on cancer diets: a review of the literature and recommendations for clinical practice. Anticancer Res. 2014;34:39–48.

    PubMed  Google Scholar 

  7. Zander ME, Wargovich MJ, Hebert JR. Methodologic considerations in the study of diet as part of complementary and alternative medicine modalities. Altern Ther Health Med. 2004;10:56–61.

    PubMed  Google Scholar 

  8. Lewis DS. On the Influence of a Diet with High Protein Content on the Kidney. Can Med Assoc J. 1921;11:682–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Addis T, Lew W. Diet and death in acute uremia. J Clin Invest. 1939;18:773–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Addis T. Glomerular nephritis: Diagnosis and treatment. London, UK: Macmillan; 1949.

  11. Piccoli GB. Patient-based continuum of care in nephrology: why read Thomas Addis’ “Glomerular Nephritis” in 2010? J Nephrol. 2010;23:164–7.

    PubMed  Google Scholar 

  12. Borst JG. Protein katabolism in uraemia; effects of protein-free diet, infections, and blood-transfusions. Lancet. 1948;1:824–9.

    Article  CAS  PubMed  Google Scholar 

  13. Giovannetti S, Maggiore Q. A low-nitrogen diet with proteins of high biological value for severe chronic uraemia. Lancet. 1964;1:1000–3.

    Article  CAS  PubMed  Google Scholar 

  14. Kerr ND, Robson A, Ashcroft R. Diet in chronic renal failure. Proc R Soc Med. 1967;60:115–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Berlyne GM, Janabi KM, Shaw AB. Dietary treatment of chronic renal failure. Proc R Soc Med. 1966;59:665–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Wright PL, Brereton PJ, Snell DEM. Effectiveness of modified Giovannetti diet compared with mixed low-protein diet. Metabolism. 1970;19:201–13.

    Article  CAS  PubMed  Google Scholar 

  17. Hood CEA, Beale DJ, Housley J, Hardwicke J. Dialysed egg as nitrogen source in dietray control of chronic renal failure. Lancet. 1969;293:479–82.

    Article  Google Scholar 

  18. Franklin SS, Gordon A, Kleeman CR, Maxwell MH. Use of a balanced low-protein diet in chronic renal failure. JAMA. 1967;202:477–84.

    Article  CAS  PubMed  Google Scholar 

  19. Berlyne GM, Gaan D, Ginks WR. Dietary treatment of chronic renal failure. Am J Clin Nutr. 1968;21:547–52.

    CAS  PubMed  Google Scholar 

  20. Mitch WE, Remuzzi G. Diets for patients with chronic kidney disease, still worth prescribing. J Am Soc Nephrol. 2004;15:234–7.

    Article  PubMed  Google Scholar 

  21. Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, Saran R, Wang AY, Yang CW. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382:260–72.

    Article  PubMed  Google Scholar 

  22. Bergstrom J. Discovery and rediscovery of low protein diet. Clin Nephrol. 1984;21:29–35.

    CAS  PubMed  Google Scholar 

  23. Walser M, Mitch WE, Maroni BJ, Kopple JD. Should protein intake be restricted in predialysis patients? Kidney Int. 1999;55:771–7.

    Article  CAS  PubMed  Google Scholar 

  24. Piccoli GB, Ferraresi M, Deagostini MC, et al. Vegetarian low-protein diets supplemented with keto analogues: a niche for the few or an option for many? Nephrol Dial Transplant. 2013;28:2295–305.

    Article  CAS  PubMed  Google Scholar 

  25. Foundation NK. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 Suppl 1):S1–266.

    Google Scholar 

  26. Eckardt KU, Berns JS, Rocco MV, Kasiske BL. Definition and classification of CKD: the debate should be about patient prognosis--a position statement from KDOQI and KDIGO. Am J Kidney Dis. 2009;53:915–20.

    Article  PubMed  Google Scholar 

  27. López-Novoa JM, Rodríguez-Peña AB, Ortiz A, Martínez-Salgado C, López Hernández FJ. Etiopathology of chronic tubular, glomerular and renovascular nephropathies: clinical implications. J Transl Med. 2011;9:13–30.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Burns A, Carson R. Maximum conservative management: a worthwhile treatment for elderly patients with renal failure who choose not to undergo dialysis. J Palliat Med. 2007;10:1245–7.

    Article  PubMed  Google Scholar 

  29. Murtagh FE, Sheerin NS, Addington-Hall J, Higginson IJ. Trajectories of illness in stage 5 chronic kidney disease: a longitudinal study of patient symptoms and concerns in the last year of life. Clin J Am Soc Nephrol. 2011;6:1580–90.

    Article  PubMed  Google Scholar 

  30. O’Hare AM, Batten A, Burrows NR, et al. Trajectories of kidney function decline in the 2 years before initiation of long-term dialysis. Am J Kidney Dis. 2012;59:513–22.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Peralta CA, Vittinghoff E, Bansal N, et al. Trajectories of kidney function decline in young black and white adults with preserved GFR: results from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Am J Kidney Dis. 2013;62:261–6.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Li L, Chang A, Rostand SG, et al. A within-patient analysis for time-varying risk factors of CKD progression. J Am Soc Nephrol. 2014;25:606–13.

    Article  CAS  PubMed  Google Scholar 

  33. Li L, Astor BC, Lewis J, et al. Longitudinal progression trajectory of GFR among patients with CKD. Am J Kidney Dis. 2012;59:504–12.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Levey AS, Inker LA, Matsushita K, et al. GFR decline as an end point for clinical trials in CKD: a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration. Am J Kidney Dis. 2014;64:821–35.

    Article  PubMed  Google Scholar 

  35. Lambers Heerspink HJ, Tighiouart H, et al. GFR decline and subsequent risk of established kidney outcomes: a meta-analysis of 37 randomized controlled trials. Am J Kidney Dis. 2014;64:860–6.

    Article  PubMed  Google Scholar 

  36. Greene T, Teng CC, Inker LA, et al. Utility and validity of estimated GFR-based surrogate time-to-event end points in CKD: a simulation study. Am J Kidney Dis. 2014;64:867–79.

    Article  PubMed  Google Scholar 

  37. Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol. 1981;241:F85–93.

    CAS  PubMed  Google Scholar 

  38. Brenner BM. Nephron adaptation to renal injury or ablation. Am J Physiol. 1985;249(3 Pt 2):F324–37.

    CAS  PubMed  Google Scholar 

  39. Klahr S, Levey AS, Beck GJ, et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med. 1994;330:877–84.

    Article  CAS  PubMed  Google Scholar 

  40. Levey AS, Greene T, Beck GJ, Caggiula AW, Kusek JW, Hunsicker LG, Klahr S. Dietary protein restriction and the progression of chronic renal disease: What have all of the results of the MDRD study shown? J Am Soc Nephrol. 1999;10:2426–39.

    CAS  PubMed  Google Scholar 

  41. Kopple JD, Greene T, Chumlea WC, et al. Relationship between nutritional status and the glomerular filtration rate: results from the MDRD study. Kidney Int. 2000;57:1688–703.

    Article  CAS  PubMed  Google Scholar 

  42. Viberti G, Bognetti E, Wiseman MJ, Dodds R, Gross JL, Keen H. Effect of protein-restricted diet on renal response to a meat meal in humans. Am J Physiol. 1987;253(3 Pt 2):F388–93.

    CAS  PubMed  Google Scholar 

  43. Bernhard J, Beaufrere B, Laville M, Fouque D. Adaptive response to a low-protein diet in predialysis chronic renal failure patients. J Am Soc Nephrol. 2001;12(6):1249–54.

    CAS  PubMed  Google Scholar 

  44. Nesrallah GE, Mustafa RA, Clark WF, et al. Canadian Society of Nephrology 2014 clinical practice guideline for timing the initiation of chronic dialysis. CMAJ. 2014;186(2):112–7.

    Article  PubMed  PubMed Central  Google Scholar 

  45. el Nahas AM, Coles GA. Dietary treatment of chronic renal failure: ten unanswered questions. Lancet. 1986;1:597–600.

    Article  PubMed  Google Scholar 

  46. Fouque D, Laville M. Low protein diets for chronic kidney disease in non diabetic adults. Cochrane Database Syst Rev. 2009;(3).

  47. Fouque D, Mitch WE. Low-protein diets in chronic kidney disease: are we finally reaching a consensus? Nephrol Dial Transplant. 2015;30:6–8.

    Article  PubMed  Google Scholar 

  48. Mennini F, Russo S, Marcellusi A, Quintaliani G, Fouque D. Economic effects of treatment of chronic kidney disease with low-protein diet. J Ren Nutr. 2014;24:313–21.

    Article  PubMed  Google Scholar 

  49. Scalone L, Borghetti F, Brunori G, et al. Cost-benefit analysis of supplemented very low-protein diet versus dialysis in elderly CKD5 patients. Nephrol Dial Transplant. 2010;25:907–13.

    Article  PubMed  Google Scholar 

  50. Giovannetti S. Dietary treatment of chronic renal failure: why is it not used more frequently? Nephron. 1985;40:1–12.

    Article  CAS  PubMed  Google Scholar 

  51. Piccoli GB, Deagostini MC, Vigotti FN, et al. Which low-protein diet for which CKD patient? An observational, personalized approach. Nutrition. 2014;30:992–9.

    Article  PubMed  Google Scholar 

  52. Maiorca R, Brunori G, Viola BF, Zubani R, Cancarini G, Parrinello G, De Carli A. Diet or dialysis in the elderly? The DODE study: a prospective randomized multicenter trial. J Nephrol. 2000;13:267–70.

    CAS  PubMed  Google Scholar 

  53. Brunori G, Viola BF, Parrinello G, et al. Efficacy and safety of a very-low-protein diet when postponing dialysis in the elderly: a prospective randomized multicenter controlled study. Am J Kidney Dis. 2007;49:569–80.

    Article  CAS  PubMed  Google Scholar 

  54. Garneata L, Mircescu G. Effect of low-protein diet supplemented with keto acids on progression of chronic kidney disease. J Ren Nutr. 2013;23:210–3.

    Article  CAS  PubMed  Google Scholar 

  55. Teplan V. Effect of keto acids on asymmetric dimethylarginine, muscle, and fat tissue in chronic kidney disease and after kidney transplantation. J Ren Nutr. 2009;19(5 Suppl):S27–9.

    Article  CAS  PubMed  Google Scholar 

  56. Teplan V, Schück O, Knotek A, Hajný J, Horácková M, Skibová J. Malý J Effects of low-protein diet supplemented with ketoacids and erythropoietin in chronic renal failure: a long-term metabolic study. Ann Transplant. 2001;6:47–53.

    CAS  PubMed  Google Scholar 

  57. Cianciaruso B, Pota A, Pisani A, et al. Metabolic effects of two low protein diets in chronic kidney disease stage 4-5--a randomized controlled trial. Nephrol Dial Transplant. 2008;23:636–44.

    Article  CAS  PubMed  Google Scholar 

  58. Bellizzi V, Chiodini P, Cupisti A, et al. Very low-protein diet plus ketoacids in chronic kidney disease and risk of death during end-stage renal disease: a historical cohort controlled study. Nephrol Dial Transplant. 2015;30:71–7.

    Article  PubMed  Google Scholar 

  59. Garneata L, Stancu A, Dragomir D, Stefan G, Mircescu G. Ketoanalogue-Supplemented Vegetarian Very Low-Protein Diet and CKD Progression. J Am Soc Nephrol. 2016. [Epub ahead of print].

  60. Giovannetti S, on behalf of the Steering Committee of the European Study Groups for the conservative treatment of chronic renal failure. Answers to ten questions on the dietary treatment of chronic renal failure. Lancet. 1986;328:1140–2.

    Article  Google Scholar 

  61. Fouque D, Aparicio M. Eleven reasons to control the protein intake of patients with chronic kidney disease. Nat Clin Pract Nephrol. 2007;3:383–92.

    Article  CAS  PubMed  Google Scholar 

  62. Aparicio M, Chauveau P, Combe C. Low protein diets and outcome of renal patients. J Nephrol. 2001;14(6):433–9.

    CAS  PubMed  Google Scholar 

  63. Chen LI, Guh JY, Wu KD, Chen YM, Kuo MC, Hwang SJ, Chen TH, Chen HC. Modification of diet in renal disease (MDRD) study and CKD epidemiology collaboration (CKD-EPI) equations for Taiwanese adults. PLoS One. 2014;9:e99645.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. McCullough ML, Feskanich D, Stampfer MJ, et al. Diet quality and major chronic disease risk in men and women: moving toward improved dietary guidance. Am J Clin Nutr. 2002;76:1261–71.

    CAS  PubMed  Google Scholar 

  65. Johnson DW. Dietary protein restriction as a treatment for slowing chronic kidney disease progression: the case against. Nephrology (Carlton). 2006;11:58–62.

    Article  CAS  Google Scholar 

  66. Maroni BJ. Protein restriction and malnutrition in renal disease: fact or fiction? Miner Electrolyte Metab. 1997;23:225–8.

    CAS  PubMed  Google Scholar 

  67. Combe C, Deforges-Lasseur C, Caix J, Pommereau A, Marot D, Aparicio M. Compliance and effects of nutritional treatment on progression and metabolic disorders of chronic renal failure. Nephrol Dial Transplant. 1993;8:412–8.

    CAS  PubMed  Google Scholar 

  68. Maroni BJ. Protein restriction in the pre-end-stage renal disease (ESRD) patient: who, when, how, and the effect on subsequent ESRD outcome. J Am Soc Nephrol. 1998;9(12 Suppl):S100–6.

    CAS  PubMed  Google Scholar 

  69. Piccoli GB. The never-ending search for the perfect dialysis. Should we move from the best treatment to the best system? Nephrol Dial Transplant. 2011;26:1128–31.

    Article  PubMed  Google Scholar 

  70. The FHN Trial Group. In-center hemodialysis six times per week versus three times per week. N Engl J Med. 2010;363:2287–300.

    Article  PubMed Central  CAS  Google Scholar 

  71. Twardowski ZJ, Misra M. “Daily” Dialysis—Lessons from a randomized, controlled trial. N Engl J Med. 2010;363:2363–4.

    Article  CAS  PubMed  Google Scholar 

  72. Milas NC, Nowalk MP, Akpele L, et al. Factors associated with adherence to the dietary protein intervention in the Modification of Diet in Renal Disease Study. J Am Diet Assoc. 1995;95:1295–300.

    Article  CAS  PubMed  Google Scholar 

  73. Coyne T, Olson M, Bradham K, Garcon M, Gregory P, Scherch L. Dietary satisfaction correlated with adherence in the Modification of Diet in Renal Disease Study. J Am Diet Assoc. 1995;95:1301–6.

    Article  CAS  PubMed  Google Scholar 

  74. Ciarambino T, Castellino P, Paolisso G, et al. Long term effects of low protein diet on depressive symptoms and quality of life in elderly Type 2 diabetic patients. Clin Nephrol. 2012;78:122–8.

    Article  CAS  PubMed  Google Scholar 

  75. Sánchez C, Aranda P, Planells E, et al. Influence of low-protein dietetic foods consumption on quality of life and levels of B vitamins and homocysteine in patients with chronic renal failure. Nutr Hosp. 2010;25:238–44.

    PubMed  Google Scholar 

  76. Kanazawa Y, Nakao T, Ohya Y, Shimomitsu T. Association of socio-psychological factors with the effects of low protein diet for the prevention of the progression of chronic renal failure. Intern Med. 2006;45:199–206.

    Article  PubMed  Google Scholar 

  77. Piccoli GB, Vigotti FN, Leone F, et al. Low-protein diets in CKD: how can we achieve them? A narrative, pragmatic review. Clin Kidney J. 2015;8:61–70.

    Article  PubMed  Google Scholar 

  78. Bellizzi V. Low-protein diet or nutritional therapy in chronic kidney disease? Blood Purif. 2013;36:41–6.

    Article  CAS  PubMed  Google Scholar 

  79. Chauveau P, Aparicio M. Benefits in nutritional interventions in patients with CKD stage 3–4. J Ren Nutr. 2011;21:20–2.

    Article  PubMed  Google Scholar 

  80. Montemurno E, Cosola C, Dalfino G, et al. What would you like to eat, Mr CKD Microbiota? A Mediterranean Diet, please! Kidney Blood Press Res. 2014;39:114–23.

    Article  CAS  PubMed  Google Scholar 

  81. Millward DJ, Jackson AA. Protein/energy ratios of current diets in developed and developing countries compared with a safe protein/energy ratio: implications for recommended protein and amino acid intakes. Public Health Nutr. 2004;7:387–405.

    Article  PubMed  Google Scholar 

  82. Volpi E, Campbell WW, Dwyer JT, et al. Is the optimal level of protein intake for older adults greater than the recommended dietary allowance? J Gerontol A Biol Sci Med Sci. 2013;68:677–81.

    Article  CAS  PubMed  Google Scholar 

  83. Keys A, Aravanis C, Buchem FSP, Blackburn H. The diet and all-causes death rate in the Seven Countries Study. Lancet. 1981;2:58–61.

  84. Trichopoulou A, Lagiou P. Healthy traditional Mediterranean diet: an expression of culture, history, and lifestyle. Nutr Rev. 1997;55:383–9.

    Article  CAS  PubMed  Google Scholar 

  85. Estruch R, Ros E, Salas-Salvadó J, et al. PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368:1279–90.

    Article  CAS  PubMed  Google Scholar 

  86. Trichopoulou A, Martínez-González MA, Tong TY, et al. Definitions and potential health benefits of the Mediterranean diet: views from experts around the world. BMC Med. 2014;12:112.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Larsson SC, Orsini N. Red meat and processed meat consumption and all-cause mortality: a meta-analysis. Am J Epidemiol. 2014;179:282–9.

    Article  PubMed  Google Scholar 

  88. Jacobson MF, Havas S, McCarter R. Changes in sodium levels in processed and restaurant foods, 2005 to 2011. JAMA Intern Med. 2013;173:1285–91.

    Article  CAS  PubMed  Google Scholar 

  89. Sylvetsky AC, Dietz WH. Nutrient-content claims--guidance or cause for confusion? N Engl J Med. 2014;371:195–8.

    Article  PubMed  Google Scholar 

  90. World Health Organization. Evaluation of certain food additives. World Health Organ Tech Rep Ser. 2012;974:1–183.

    Google Scholar 

  91. Watson D. Vegan News, No. 1, November 1944.

  92. Orlich MJ, Singh PN, Sabaté J, et al. Vegetarian Dietary Patterns and the Risk of Colorectal Cancers. JAMA Intern Med. 2015. doi: 10.1001/jamainternmed.2015.59. [Epub ahead of print].

  93. Le LT, Sabaté J. Beyond meatless, the health effects of vegan diets: findings from the Adventist cohorts. Nutrients. 2014;6:2131–47.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Gilsing AM, Weijenberg MP, Goldbohm RA, Dagnelie PC, van den Brandt PA, Schouten LJ. The Netherlands Cohort Study − Meat Investigation Cohort; a population-based cohort over-represented with vegetarians, pescetarians and low meat consumers. Nutr J. 2013;12:156.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Tonstad S, Butler T, Yan R, Fraser GE. Type of vegetarian diet, body weight, and prevalence of type 2 diabetes. Diabetes Care. 2009;32:791–6.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Barsotti G, Morelli E, Cupisti A, Meola M, Dani L, Giovannetti S. A low-nitrogen low-phosphorus Vegan diet for patients with chronic renal failure. Nephron. 1996;74:390–4.

    Article  CAS  PubMed  Google Scholar 

  97. Anderson JW, Blake JE, Turner J, Smith BM. Effects of soy protein on renal function and proteinuria in patients with type 2 diabetes. Am J Clin Nutr. 1998;68(6 Suppl):1347S–53.

    CAS  PubMed  Google Scholar 

  98. Azadbakht L, Esmaillzadeh A. Soy-protein consumption and kidney-related biomarkers among type 2 diabetics: a crossover, randomized clinical trial. J Ren Nutr. 2009;19(6):479–86. doi:10.1053/j.jrn.2009.06.002.

    Article  CAS  PubMed  Google Scholar 

  99. Cupisti A, Ghiadoni L, D’Alessandro C, et al. Soy protein diet improves endothelial dysfunction in renal transplant patients. Nephrol Dial Transplant. 2007;22:229–34.

    Article  CAS  PubMed  Google Scholar 

  100. Moe SM, Zidehsarai MP, Chambers MA, et al. Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. Clin J Am Soc Nephrol. 2011;6:257–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Soroka N, Silverberg DS, Greemland M, Birk Y, Blum M, Peer G, Iaina A. Comparison of a vegetable-based (soya) and an animal-based low-protein diet in predialysis chronic renal failure patients. Nephron. 1998;79:173–80.

    Article  CAS  PubMed  Google Scholar 

  102. Buzio C, Mutti A, Perazzoli F, Alinovi R, Arisi L, Negro A. Protein-induced changes in kidney function depend on the time of administration but not on the dietary source. Nephron. 1990;56:234–40.

    Article  CAS  PubMed  Google Scholar 

  103. King AJ, Levey AS. Dietary protein and renal function. J Am Soc Nephrol. 1993;3:1723–37.

    CAS  PubMed  Google Scholar 

  104. Chauveau P, Combe C, Fouque D, Aparicio M. Vegetarianism: advantages and drawbacks in patients with chronic kidney diseases. J Ren Nutr. 2013;23:399–405.

    Article  PubMed  Google Scholar 

  105. Zhang J, Liu J, Su J, Tian F. The effects of soy protein on chronic kidney disease: a meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2014;68:987–93.

    Article  CAS  PubMed  Google Scholar 

  106. Causso C, Arrieta F, Hernández J, et al. Severe ketoacidosis secondary to starvation in a frutarian patient. Nutr Hosp. 2010;25:1049–52.

    CAS  PubMed  Google Scholar 

  107. Sitprija V, Suvanpha R. Low protein diet and chronic renal failure in Buddhist monks. Br Med J (Clin Res Ed). 1983;287(6390):469–71.

    Article  CAS  Google Scholar 

  108. Krucoff MW, Crater SW, Gallup D, et al. Music, imagery, touch, and prayer as adjuncts to interventional cardiac care: the Monitoring and Actualisation of Noetic Trainings (MANTRA) II randomised study. Lancet. 2005;366(9481):211–7.

    Article  PubMed  Google Scholar 

  109. Black DS, Slavich GM. Mindfulness meditation and the immune system: a systematic review of randomized controlled trials. Ann N Y Acad Sci. 2016. doi:10.1111/nyas.12998 [Epub ahead of print].

    PubMed  Google Scholar 

  110. Craig WJ, Mangels AR, Association AD. Position of the American Dietetic Association: vegetarian diets. J Am Diet Assoc. 2009;109:1266–82.

    Article  CAS  PubMed  Google Scholar 

  111. American Dietetic Association; Dietitians of Canada. Position of the American Dietetic Association and Dietitians of Canada: vegetarian diets. Can J Diet Pract Res. 2003;64:62–81.

    Article  Google Scholar 

  112. Craig WJ. Nutrition concerns and health effects of vegetarian diets. Nutr Clin Pract. 2010;25:613–20.

    Article  PubMed  Google Scholar 

  113. Piccoli GB, Clari R, Vigotti FN, et al. Vegan-vegetarian diets in pregnancy: danger or panacea? A systematic narrative review. BJOG. 2015;122:623–33.

    Article  CAS  PubMed  Google Scholar 

  114. Walser M, Mitch WE, Abras E. Supplements containing amino acids and keto acids in the treatment of chronic uremia. Kidney Int Suppl. 1983;16:S285–9.

    CAS  PubMed  Google Scholar 

  115. Aparicio M, Bellizzi V, Chauveau P, et al. Keto acid therapy in predialysis chronic kidney disease patients: final consensus. J Ren Nutr. 2012;22(2 Suppl):S22–4.

    Article  PubMed  Google Scholar 

  116. Liou HH. What can a keto acid/amino acid-supplemented protein-restricted diet do for the “butterfly effect” in chronic kidney disease patients? J Ren Nutr. 2009;19(5 Suppl):S15–8.

    Article  CAS  PubMed  Google Scholar 

  117. Shah AP, Kalantar-Zadeh K, Kopple JD. Is There a Role for Ketoacid Supplements in the Management of CKD? Am J Kidney Dis. 2015.

  118. Piccoli GB, Attini R, Vasario E, et al. Vegetarian supplemented low-protein diets. A safe option for pregnant CKD patients: report of 12 pregnancies in 11 patients. Nephrol Dial Transplant. 2011;26:196–205.

    Article  CAS  PubMed  Google Scholar 

  119. Piccoli GB, Leone F, Attini R, et al. Association of low-protein supplemented diets with fetal growth in pregnant women with CKD. Clin J Am Soc Nephrol. 2014;9:864–73.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Piccoli GB, Motta D, Martina G, et al. Low-protein vegetarian diet with alpha-chetoanalogues prior to pre-emptive pancreas-kidney transplantation. Rev Diabet Stud. 2004;1:95–102.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Piccoli GB, Guzzo G, Vigotti FN, et al. Tailoring dialysis and resuming low-protein diets may favor chronic dialysis discontinuation: Report on three cases. Hemodial Int. 2014;18(3):590–5.

    Article  PubMed  Google Scholar 

  122. Schefold JC, Zeden JP, Fotopoulou C, et al. Increased indoleamine 2, 3-dioxygenase (IDO) activity and elevated serum levels of tryptophan catabolites in patients with chronic kidney disease: a possible link between chronic inflammation and uraemic symptoms. Nephrol Dial Transplant. 2009;24:1901–8.

    Article  CAS  PubMed  Google Scholar 

  123. Sallée M, Dou L, Cerini C, Poitevin S, Brunet P, Burtey S. The aryl hydrocarbon receptor-activating effect of uremic toxins from tryptophan metabolism: a new concept to understand cardiovascular complications of chronic kidney disease. Toxins (Basel). 2014;6:934–49.

    Article  CAS  Google Scholar 

  124. Aparicio M, Cano NJ, Cupisti A, et al. Keto-acid therapy in predialysis chronic kidney disease patients: consensus statements. J Ren Nutr. 2009;19(5 Suppl):S33–5.

    Article  PubMed  Google Scholar 

  125. Willcox DC, Willcox BJ, Todoriki H, Suzuki M. The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load. J Am Coll Nutr. 2009;28(Suppl):500S–16.

    Article  CAS  PubMed  Google Scholar 

  126. Miyagi S, Iwama N, Kawabata T, Hasegawa K. Longevity and diet in Okinawa, Japan: the past, present and future. Asia Pac J Public Health. 2003;15(Suppl):S3–9.

    Article  PubMed  Google Scholar 

  127. Gavrilova NS, Gavrilov LA. Comments on dietary restriction, Okinawa diet and longevity. Gerontology. 2012;58:221–3. discussion 224–6.

    Article  PubMed  Google Scholar 

  128. Willcox BJ, Willcox DC, Todoriki H, et al. Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world’s longest-lived people and its potential impact on morbidity and life span. Ann N Y Acad Sci. 2007;1114:434–55.

    Article  CAS  PubMed  Google Scholar 

  129. Sotos-Prieto M, Moreno-Franco B, Ordovás JM, León M, Casasnovas JA, Peñalvo JL. Design and development of an instrument to measure overall lifestyle habits for epidemiological research: the Mediterranean Lifestyle (MEDLIFE) index. Public Health Nutr. 2015;18:959–67.

    Article  PubMed  Google Scholar 

  130. Fujita R, Braun KL, Hughes CK. The traditional Hawaiian diet: a review of the literature. Pac Health Dialog. 2004;11:250–9.

    PubMed  Google Scholar 

  131. McKerchar C, Bowers S, Heta C, Signal L, Matoe L. Enhancing Māori food security using traditional kai. Glob Health Promot. 2014 Aug 1. pii: 1757975914543573. [Epub ahead of print].

  132. Laird BD, Goncharov AB, Egeland GM, Chan HM. Dietary advice on Inuit traditional food use needs to balance benefits and risks of mercury, selenium, and n3 fatty acids. J Nutr. 2013;143:923–30.

    Article  CAS  PubMed  Google Scholar 

  133. Li JR, Hsieh YH. Traditional Chinese food technology and cuisine. Asia Pac J Clin Nutr. 2004;13:147–55.

    PubMed  Google Scholar 

  134. Chen C. Eating patterns-- a prognosis for China. Asia Pac J Clin Nutr. 1995;4 Suppl 1:24–8.

    PubMed  Google Scholar 

  135. Mahadevan M, Blair D, Raines ER. Changing food habits in a South Indian Hindu Brahmin community: a case of transitioning gender roles and family dynamics. Ecol Food Nutr. 2014;53:596–617.

    Article  PubMed  Google Scholar 

  136. Ethan D, Basch CH, Rajan S, Samuel L, Hammond RN. A comparison of the nutritional quality of food products advertised in grocery store circulars of high-versus low-income New York City zip codes. Int J Environ Res Public Health. 2013;11:537–47.

    Article  PubMed  PubMed Central  Google Scholar 

  137. D’Alessandro C, Rossi A, Innocenti M, et al. Dietary protein restriction for renal patients: don’t forget protein-free foods. J Ren Nutr. 2013;23:367–71.

    Article  PubMed  CAS  Google Scholar 

  138. Giovannetti S. Low protein diet in chronic uremia: a historical survey. Contrib Nephrol. 1986;53:1–6.

    Article  CAS  PubMed  Google Scholar 

  139. Van Duyn MA. Acceptability of selected low-protein products for use in a potential diet therapy for chronic renal failure. J Am Diet Assoc. 1987;87:909–14.

    PubMed  Google Scholar 

  140. Giordano M, Ciarambino T, Castellino P, Paolisso G. Light and shadows of dietary protein restriction in elderly with chronic kidney disease. Nutrition. 2013;29:1090–3.

    Article  CAS  PubMed  Google Scholar 

  141. Thilly N. Low-protein diet in chronic kidney disease: from questions of effectiveness to those of feasibility. Nephrol Dial Transplant. 2013;28:2203–5.

    Article  CAS  PubMed  Google Scholar 

  142. Cianciaruso B, Capuano A, D’Amaro E, et al. Dietary compliance to a low protein and phosphate diet in patients with chronic renal failure. Kidney Int Suppl. 1989;27:S173–6.

    CAS  PubMed  Google Scholar 

  143. Giordano M, Ciarambino T, Castellino P, et al. Long-term effects of moderate protein diet on renal function and low-grade inflammation in older adults with type 2 diabetes and chronic kidney disease. Nutrition. 2014;30:1045–9.

    Article  CAS  PubMed  Google Scholar 

  144. Cupisti A, Morelli E, Meola M, Barsotti M, Barsotti G. Vegetarian diet alternated with conventional low-protein diet for patients with chronic renal failure. J Ren Nutr. 2002;12:32–7.

    Article  PubMed  Google Scholar 

  145. http://www.medicinenet.com/script/main/art.asp?articlekey=33619 (last accessed 5th/04/2015).

  146. http://www.cancer.gov/dictionary?cdrid=454747 (last accessed 5th/04/2015).

  147. Segen’s Medical Dictionary. © 2012 Farlex, Inc.

  148. The McGraw-Hill Dictionary of Scientific and Technical Terms. Seventh Edition: Mc Graw-Hill, New York;2012.

  149. http://www.nlm.nih.gov/medlineplus/complementaryandalternativemedicine.html (last accessed 5th/04/2015).

  150. https://nccih.nih.gov/health/whatiscam (last accessed 5th/04/2015).

  151. Moorthi RN, Armstrong CL, Janda K, Ponsler-Sipes K, Asplin JR, Moe SM. The effect of a diet containing 70 % protein from plants on mineral metabolism and musculoskeletal health in chronic kidney disease. Am J Nephrol. 2014;40:582–91.

    Article  CAS  PubMed  Google Scholar 

  152. Jones L, Moschonis G, Oliveira A, et al. The influence of early feeding practices on healthy diet variety score among pre-school children in four European birth cohorts. Public Health Nutr. 2014;20:1–11.

    Google Scholar 

  153. Di Daniele N, Di Renzo L, Noce A, et al. Effects of Italian Mediterranean organic diet vs. low-protein diet in nephropathic patients according to MTHFR genotypes. J Nephrol. 2014;27:529–36.

    Article  PubMed  CAS  Google Scholar 

  154. Kovesdy CP. Traditional and novel dietary interventions for preventing progression of chronic kidney disease. J Ren Nutr. 2013;23:241–5.

    Article  PubMed  Google Scholar 

  155. Willingham F. The dietary management of patients with diabetes and renal disease: challenges and practicalities. J Ren Care. 2012;38 Suppl 1:40–51.

    Article  PubMed  Google Scholar 

  156. Ikizler TA. Protein and energy intake in advanced chronic kidney disease: how much is too much? Semin Dial. 2007;20:5–11.

    Article  PubMed  Google Scholar 

  157. Walser M, Hill S. Can renal replacement be deferred by a supplemented very low protein diet? J Am Soc Nephrol. 1999;10:110–6.

    CAS  PubMed  Google Scholar 

  158. Sidorenkov G, Navis G. Safety of ACE inhibitor therapies in patients with chronic kidney disease. Expert Opin Drug Saf. 2014;13:1383–95.

    Article  CAS  PubMed  Google Scholar 

  159. Mitch WE. Beneficial responses to modified diets in treating patients with chronic kidney disease. Kidney Int Suppl. 2005;94:S133–5.

    Article  PubMed  Google Scholar 

  160. Friedman AN. New evidence for an old strategy to help delay the need for dialysis. Am J Kidney Dis. 2007;49:563–5.

    Article  PubMed  Google Scholar 

  161. De las Cuevas C. Towards a clarification of terminology in medicine taking behavior: compliance, adherence and concordance are related although different terms with different uses. Curr Clin Pharmacol. 2011;6:74–7.

    Article  PubMed  Google Scholar 

  162. Khair K. Compliance, concordance and adherence: what are we talking about? Haemophilia. 2014;20:601–3.

    Article  CAS  PubMed  Google Scholar 

  163. Chakrabarti S. What’s in a name? Compliance, adherence and concordance in chronic psychiatric disorders. World J Psychiatry. 2014;4:30–6.

    Article  PubMed  PubMed Central  Google Scholar 

  164. Patwardhan B, Ayurveda GCP. Guidelines: Need for freedom from RCT ascendancy in favor of whole system approach. J Ayurveda Integr Med. 2011;22:1–4.

    Article  Google Scholar 

  165. Gray JA. The shift to personalised and population medicine. Lancet. 2013;382:200–1.

    Article  PubMed  Google Scholar 

  166. Kitsios GD, Kent DM. Personalised medicine: not just in our genes. BMJ 2012;e2161

  167. Basch E. Toward patient-centered drug development in oncology. N Engl J Med. 2013;369:397–400.

    Article  CAS  PubMed  Google Scholar 

  168. Lin GA. Patient education: one size does not fit all. JAMA Intern Med. 2013;173:1376.

    Article  PubMed  Google Scholar 

  169. Black N. Why we need observational studies to evaluate the effectiveness of health care. BMJ. 1996;312:1215–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Benson K, Hartz AJ. A comparison of observational studies and randomized, controlled trials. N Engl J Med. 2000;342:1878–86.

    Article  CAS  PubMed  Google Scholar 

  171. Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med. 2000;342:1887–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Barton S. Which clinical studies provide the best evidence? The best RCT still trumps the best observational study. BMJ. 2000;321:255–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Verhoef MJ, Lewith G, Ritenbaugh C, Boon H, Fleishman S, Leis A. Complementary and alternative medicine whole systems research: beyond identification of inadequacies of the RCT. Complement Ther Med. 2005;13:206–12.

    Article  PubMed  Google Scholar 

  174. Verhoef MJ, Casebeer AL, Hilsden RJ. Assessing efficacy of complementary medicine: adding qualitative research methods to the “Gold Standard”. J Altern Complement Med. 2002;8:275–81.

    Article  PubMed  Google Scholar 

  175. Ritenbaugh C, Verhoef M, Fleishman S, Boon H, Leis A. Whole systems research: a discipline for studying complementary and alternative medicine. Altern Ther Health Med. 2003;9:32–6.

    PubMed  Google Scholar 

  176. Bell IR, Koithan M. Models for the study of whole systems. Integr Cancer Ther. 2006;5:293–307.

    Article  PubMed  Google Scholar 

  177. King M, Nazareth I, Lampe F, et al. Conceptual framework and systematic review of the effects of participants’ and professionals’ preferences in randomised controlled trials. Health Technol Assess. 2005;9:1–186. iii-iv.

    Article  CAS  PubMed  Google Scholar 

  178. Cao HJ, Liu JP, Hu H, Wang NS. Using a partially randomized patient preference study design to evaluate the therapeutic effect of acupuncture and cupping therapy for fibromyalgia: study protocol for a partially randomized controlled trial. Trials. 2014;15:280.

    Article  PubMed  PubMed Central  Google Scholar 

  179. Hubacher D, Spector H, Monteith C, Chen PL, Hart C. Rationale and enrollment results for a partially randomized patient preference trial to compare continuation rates of short-acting and long-acting reversible contraception. Contraception. 2015;91:185–92.

    Article  PubMed  Google Scholar 

  180. Leiva-Fernández F, Leiva-Fernández J, Zubeldia-Santoyo F, García-Ruiz A, Prados-Torres D, Barnestein-Fonseca P. Efficacy of two educational interventions about inhalation techniques in patients with chronic obstructive pulmonary disease (COPD). TECEPOC: study protocol for a partially randomized controlled trial (preference trial). Trials. 2012;13:64.

    Article  PubMed  PubMed Central  Google Scholar 

  181. Klein S, Cumming GP, Lee AJ, Alexander DA, Bolsover D. Evaluating the effectiveness of a web-based intervention to promote mental wellbeing in women and partners following miscarriage, using a modified patient preference trial design: an external pilot. BJOG. 2012;119:762–7.

    Article  CAS  PubMed  Google Scholar 

  182. Halpern SD. Evaluating preference effects in partially unblinded, randomized clinical trials. J Clin Epidemiol. 2003;56:109–15.

    Article  PubMed  Google Scholar 

  183. Mu W, Shang H. Understanding patient values and the manifestations in clinical research with traditional chinese medicine-with practical suggestions for trial design and implementation. Evid Based Complement Alternat Med. 2013;2013:847273.

    Article  PubMed  PubMed Central  Google Scholar 

  184. Borradaile KE, Halpern SD, Wyatt HR, et al. Relationship between treatment preference and weight loss in the context of a randomized controlled trial. Obesity (Silver Spring). 2012;20:1218–22.

    Article  Google Scholar 

  185. Preference Collaborative Review Group. Patients’ preferences within randomised trials: systematic review and patient level meta-analysis. BMJ. 2008;337:a1864.

    Article  PubMed Central  Google Scholar 

  186. Gemmell I, Dunn G. The statistical pitfalls of the partially randomized preference design in non-blinded trials of psychological interventions. Int J Methods Psychiatr Res. 2011;20:1–9.

    Article  PubMed  Google Scholar 

  187. Charon R. The patient-physician relationship. Narrative medicine: a model for empathy, reflection, profession, and trust. JAMA. 2001;286:1897–902.

    Article  CAS  PubMed  Google Scholar 

  188. Charon R. What to do with stories: the sciences of narrative medicine. Can Fam Physician. 2007;53:1265–7.

    PubMed  PubMed Central  Google Scholar 

  189. Charon R, Wyer P, Working Group NEBM. Narrative evidence based medicine. Lancet. 2008;371:296–7.

    Article  PubMed  Google Scholar 

  190. Meisel ZF, Karlawish J. Narrative vs evidence-based medicine--and, not or. JAMA. 2011;306:2022–3.

    Article  CAS  PubMed  Google Scholar 

  191. Spiegel DM, Brady K. Calcium balance in normal individuals and in patients with chronic kidney disease on low-and high-calcium diets. Kidney Int. 2012;81(11):1116–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Filipowicz R, Beddhu S. Optimal nutrition for predialysis chronic kidney disease. Adv Chronic Kidney Dis. 2013;20(2):175–80.

    Article  PubMed  Google Scholar 

  193. Cupisti A, Kalantar-Zadeh K. Management of natural and added dietary phosphorus burden in kidney disease. Semin Nephrol. 2013;33:180–90.

    Article  CAS  PubMed  Google Scholar 

  194. Sarathy S, Sullivan C, Leon JB, Sehgal AR. Fast food, phosphorus-containing additives, and the renal diet. J Ren Nutr. 2008;18:466–70.

    Article  PubMed  Google Scholar 

  195. D’Alessandro C, Piccoli GB, Cupisti A. The “phosphorus pyramid”: a visual tool for dietary phosphate management in dialysis and CKD patients. BMC Nephrol. 2015;16:9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  196. Girelli D, Olivieri O, Stanzial AM, et al. Low platelet glutathione peroxidase activity and serum selenium concentration in patients with chronic renal failure: relations to dialysis treatments, diet and cardiovascular complications. Clin Sci (Lond). 1993;84(6):611–7.

    Article  CAS  Google Scholar 

  197. Huang X, Sjögren P, Ärnlöv J, et al. Serum fatty acid patterns, insulin sensitivity and the metabolic syndrome in individuals with chronic kidney disease. J Intern Med. 2014;275(1):71–83.

    Article  CAS  PubMed  Google Scholar 

  198. Saikumar JH, Kovesdy CP. Bicarbonate Therapy in End-Stage Renal Disease: Current Practice Trends and Implications. Semin Dial. 2015. doi: 10.1111/sdi.12373. [Epub ahead of print].

  199. Ciarambino T, Ferrara N, Castellino P, Paolisso G, Coppola L, Giordano M. Effects of a 6-days-a-week low protein diet regimen on depressive symptoms in young-old type 2 diabetic patients. Nutrition. 2011;27(1):46–9.

    Article  CAS  PubMed  Google Scholar 

  200. Paes-Barreto JG, Silva MI, Qureshi AR, Bregman R, Cervante VF, Carrero JJ, Avesani CM. Can renal nutrition education improve adherence to a low-protein diet in patients with stages 3 to 5 chronic kidney disease? J Ren Nutr. 2013;23:164–71.

    Article  PubMed  Google Scholar 

  201. Pisani A, Riccio E, Bellizzi V, et al. 6-tips diet: a simplified dietary approach in patients with chronic renal disease. Clin Exp Nephrol: A clinical randomized trial; 2015 [Epub ahead of print].

    Google Scholar 

  202. Kalantar-Zadeh K. Patient education for phosphorus management in chronic kidney disease. Patient Prefer Adherence. 2013;7:379–90.

    Article  PubMed  PubMed Central  Google Scholar 

  203. Porta N, Bonet C, Cobo E. Discordance between reported intention-to-treat and per protocol analyses. J Clin Epidemiol. 2007;60(7):663–9.

    Article  PubMed  Google Scholar 

  204. Sedgwick P. What is intention to treat analysis? BMJ. 2013;346:f3662.

    Article  Google Scholar 

Download references

Acknowledgement

Valerie Perricone for her language editing.

Funding

No specific funding was employed for this study; the general expenses were from an ex-60 % grant to Giorgina Piccoli.

Authors’ contributions

GBP designed and drafted the study; FVN (MD, master in CAMs), SR (MD), IC, FL, CDA (dietetitians) reviewed and added to the draft, where appropriate; DG and MN (MDs) worked on the methodological part, and retrieved and discussed the EBM papers; NC, GM, NC (University library): carried out the searches on diets and CAMs and retrieved the papers; AC and PA (MD) reviewed and discussed the final draft, from the point of view of the nephrologist (CA) and of the nutritionist (AP). All authors read and approved the final manuscript.

Competing interests

GB Piccoli and A Cupisti belongs to the Ketosteril advisory board (Fresenus Kabi); Federica Neve Vigotti received a Fresenus Kabi research fellowship through a University grant to GB Piccoli (University of Torino).

The other Authors have no potential competing interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Giorgina Barbara Piccoli.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Piccoli, G.B., Capizzi, I., Vigotti, F.N. et al. Low protein diets in patients with chronic kidney disease: a bridge between mainstream and complementary-alternative medicines?. BMC Nephrol 17, 76 (2016). https://doi.org/10.1186/s12882-016-0275-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12882-016-0275-x

Keywords