Dietary protein restriction in chronic kidney disease: one size does not fit all

Twenty-five years after the publication of the seminal Modification of Diet in Renal Disease (MDRD) Study, which suggested a small benefit of dietary protein restriction on the progression of chronic kidney disease (CKD) [1], there are considerable variations from one centre to another, even from one nephrologist to another, in the prescription of protein restriction for various matters. These are linked to scientific and medical considerations, but also to feasibility, acceptance by patients and the organization of health care. In this context, sharing of expertise by centres that have long-term experience with protein restriction might be useful to share, even in the perspective of reassessment of the effect of protein restriction in CKD in a properly designed randomized clinical trial (RCT) [2]. In this issue of Nephrology Dialysis Transplantation, Piccoli et al. [3] report the experience of the use of protein restriction in 422 patients with CKD Stages 1–5D in four centres in Italy. The study is focused on quality of life (QoL) and dietary satisfaction of these patients, i.e. objectives different from most studies that have evaluated the impact of protein restriction on CKD progression and other clinical endpoints, including end-stage kidney disease (ESKD).

As a matter of fact, the debate over the effectiveness of protein restriction is far from closed; in a recent Cochrane review, Palmer et al. [2] stated that ‘dietary interventions may prevent one person in every 3000 treated for one year avoiding ESKD, although the certainty in this effect was very low’. Nevertheless, there were significant beneficial effects of protein restriction on systolic and diastolic blood pressure, estimated glomerular filtration rate (eGFR) and low-density lipoprotein cholesterol. In an even more recent Cochrane review, it was found that very low protein intake compared with a low protein intake probably reduces the number of patients who reach ESKD (165 per 1000 fewer reached ESKD), but the evidence was of moderate certainty [4]. Both reviews conclude that large-scale pragmatic RCTs are needed to test the effects of dietary interventions on patient outcomes [2, 4]. This study contains important information to be taken into account if such RCTs are to be performed, given the experience of our Italian colleagues, with the present cohort being one of the largest reported so far.

The first information is that protein restriction may not be proposed to all patients with CKD, since it is not adapted to patients with high comorbidities, malnutrition or poor life expectancy and since patients may not want to limit their protein intake [3]. This latter aspect may depend on cultural background and habits. Global protein intake is two times higher in industrialized countries, with meat intake being three times higher. In consumers of Mediterranean diets, such as in Italy, an equilibrium exists between plant and animal protein, and it is easier to reduce protein intake than in meat eaters [5]. Protein restriction is therefore a relative concept [6], depending on regional and personal dietary protein consumption. In this respect, the authors are right to highlight the Mediterranean diet of these elderly patients, most of them being >70 years of age and used to eating such a diet. Protein intake in the Mediterranean diet is much lower than in the diets of Northern and Eastern Europe and of North America [6]: there are selection biases in this study, the first being that it was performed in Italy and the second being that patients were selected in the different centres. In our opinion, this selection may not be a bias, but a condition of feasibility.

The second important factor is that protein restriction may not be limited to two types of diets as in the MDRD study, in which moderate protein restriction at 0.58 g/kg body weight/day or a very low protein diet (VLPD) of 0.28 g/kg/day supplemented with keto acids were prescribed to patients according to their eGFR [1], in a quite rigid manner, which is mandatory in a properly conducted RCT. Here, various amounts and types of protein restriction were proposed to patients according to different parameters, including age, comorbidities and centre. Table 1 in Piccoli et al. [3] synthesizes these six types of protein restriction, one of them being ‘tailored solutions’, i.e. a diet tailored to patients’ needs and taste. Thus it is not surprising that diet satisfaction was best with these tailored diets, while VLPD was the least satisfactory, given its impact in terms of diet modification and social consequences and despite the possibility of having one unrestricted meal per week (the ‘blessed day’). It must be highlighted that vegan diets are well accepted by patients. This type of diet has many potential benefits that were recently reviewed by our team [7]. The authors do not detail the role of dieticians, who do not seem to be present in the centre with the lowest satisfaction scores. However, it might be hypothesized or hoped that dieticians’ interventions helped patients to enjoy their diet, or at least to be compliant with it, as suggested by a secondary analysis of the MDRD study [8].

An important aspect of this study is that it was performed in centres with long-term experience that allowed nephrologists and dieticians to further adapt diet prescriptions to patients’ needs. Examples of adaptations are, for instance, obese patients in whom an average between real and ideal body weight was used when body mass index was >40 kg/m², or older patients in whom prescribed caloric intake was lower than in other patients or the increase in protein intake over time from 0.59 to 0.70 g/kg/day [3]. How can these considerations be reconciled with the constraints of an RCT evaluating the effects of protein restriction? We believe that the only possibility would be to evaluate the impact of a restriction of protein intake relative to the usual intake of each patient.

The third factor is that protein restriction might be used in a wide range of CKD stages, as in this study, protein restriction was used from CKD Stage 1 in patients with proteinuria resistant to renin–angiotensin system inhibitors to CKD Stage 5D where patients were treated once weekly by dialysis. It should be noted that some patients were grafted pre-emptively, potentially because of their relatively stable renal function. Given the diversity of CKD stages and conditions in this study and the variety of protein-restricted diets used, the only parameters that made sense to be studied were QoL and patients’ satisfaction, i.e. patient-related outcome measures. The study by Piccoli et al. [3] clearly shows that these diets are accepted by (selected) patients and that they have a limited impact on QoL. One may consider that the issue of QoL is not marginal in the setting of CKD, since numerous studies have shown that patients treated by dialysis have the poorest QoL of patients with chronic illnesses [9]. QoL needs to be measured when the effect of protein restriction is evaluated; delaying the onset of ESKD through protein restriction or delaying dialysis initiation through an impact on uraemic symptoms will affect QoL.

In conclusion, the study by Piccoli et al. [3] shows that dietary restriction might be used in patients with CKD over long periods of time, provided that these patients are properly selected, that the prescribed diet is tailored to the patients’ needs, habits and taste and that patients are adequately followed by a team including at least a nephrologist and a dietician. These minimal conditions need to be considered in the design of RCTs evaluating the impact of protein restriction on clinical and patient-related outcomes in CKD, despite their complexity.

CONFLICT OF INTEREST STATEMENT

None declared.

(See related article by Piccoli et al. Dietary satisfaction and quality of life in chronic kidney disease patients on low-protein diets: a multicentre study with long-term outcome data (TOrino-Pisa study). Nephrol Dial Transplant 2020; 35: 790--802)

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