Historical background of low-protein diets for renal diseases
Dietary protein restriction is the mainstay of the nutritional therapy for CKD. Since the 19
th century it had been realized that uremic syndrome derives from the retention of molecules and toxins resulting from the catabolism of exogenous proteins, usually excreted with the urine. However, it was only in the 1960s, that Giovannetti and Maggiore suggested the low-protein diet as a therapy for advanced CKD [
1]. At that time dialysis was still in the experimental stage and only a small number of patients could benefit. A protein restricted diet providing adequate amounts of aminoacids and energy supply was therefore the only widespread means to alleviate uremic symptoms and to prolong survival [
1].
Thereafter, dialysis techniques and facilities, as well as kidney transplantation, rapidly developed as replacement therapies for ESRD. Although these therapies came to represent milestones in the history of modern medicine, at the same time they reduced interest in the low-protein diet as a treatment for advanced CKD. Nonetheless, with the aid of the Brenner theory and its central aim of reducing protein-related glomerular hyperfiltration and hypertrophy, the low-protein diet was seen as a means to protect residual renal function and to slow down the CKD progression to ESRD [
2]. Later, the availability of renoprotective and anti-proteinuric drugs (RAS inhibitors) again limited the implementation of dietary intervention in CKD. However, the low-protein diet still remains a viable means in the prevention or treatment of several metabolic and clinical abnormalities during CKD, as well as in the reduction of proteinuria, either in association with RAS inhibitors or in patients who cannot be treated with these drugs [
3].
It is noteworthy that urea (as a marker of uremic toxins) reduction is not the only aim of the low protein diet. Indeed, in the early 1980s Maschio and Barsotti highlighted the importance of protein restriction in the reduction of phosphorus intake in moderate to advanced CKD [
4,
5]. This aspect, neglected for many years, now enjoys significant renewed interest stimulated by the evidence of the key role of phosphorus retention in the pathogenesis of the so-called CKD-MBD and in the progression of renal disease [
6,
7].
Dietary sodium restriction is another aspect of the nutritional therapy for CKD, as it allows better management of sodium and water retention, blood pressure control, and reduction of proteinuria [
8].
Last but not least, it is of paramount importance to underline that the renal diet is not only a matter of restriction. It is also essential to ensure that the full energy requirement is met in CKD patients (whether on low-protein or following autonomous diets), in order to prevent protein catabolism, maintain neutral nitrogen balance, and to maintain adequate nutritional status and body composition [
9]. Contrary to just prescribing a low-protein diet, a comprehensive nutritional approach for CKD patients is to be considered mandatory.
An important improvement in the dietary treatment for advanced CKD was the availability of protein-free foods [
10]. These products consist of carbohydrates (starch) and are virtually free of nitrogen, potassium, phosphorus and are also low in salt content. They effectively replace analogous staple foods (bread, pasta, biscuits) making it possible to reduce the intake of protein of low biological value, and thereby allowing adequate intake of animal proteins whilst ensuring a high energy intake. Such protein-free products have been widely available in Italy for some time and, nowadays, can also be obtained in other countries around the world. In the early years, protein-free products were far less palatable than corresponding foods, thus limiting patient adherence. In the last few years, however, these foods were further developed and their palatability much improved. It is in fact notable that the risk of “malnutrition” associated with a low-protein diet is usually the result of an insufficient energy intake rather than of a low protein supply. Hence, when protein-free products are refused by patients or are unavailable, a vegan diet can be offered as an alternative, providing low protein (0.7/kg/dayay), low-phosphorus and an adequate support of essential aminoacids derived from a strict combination of cereals and legumes [
11]. At the same total protein content, the vegan diet allows more favourable effects including a lesser net acid production, a greater anti-proteinuric effect and a lower net intestinal absorption of phosphorus [
12]. The observation that the vegan diet has effects similar to that of a conventional low-protein diet also permits an alternation between the two, thereby increasing the choice of foods and, consequently, the patients’ adherence [
13].
Finally, when a modest restriction of protein and phosphorus is not enough (as in the case of severe reduction of renal function), a very low-protein (0.3 g/kg/day), very low-phosphorus diet supplemented with calcium, folates, group B vitamins and mixtures of essential aminoacids and ketoacids, can be prescribed [
14,
15].
Though low
-protein diets supply low amounts of proteins they are high in carbohydrates, which are contraindicated for patients with nephrotic syndrome or diabetes mellitus. However, in the late 1980s the beneficial effects of protein restriction on glucose metabolism [
16‐
18], and also proteinuria [
19‐
22] were proven. Hence, the change in the quantity and quality of dietary proteins is indicated even in diabetic and proteinuric renal diseases.
In summary, protein restriction, including reduction of phosphorus and salt, together with adequacy of energy intake, represent the general characteristics of the nutritional therapy for CKD patients. Moreover, the severity of restrictions and the amount and quality of food and supplements should be defined in accordance with the advancement of CKD and the clinical conditions under which it is observed.
Epidemiological data show that CKD is very common, particularly in elderly patients with comorbidities, including cardiovascular diseases, diabetes and hypertension. At the present time, the CKD population is much older in comparison to previous decades [
23,
24], a factor that introduces psychological and socio-economic elements that must be dealt with. Thus, the nutritional management of renal patients becomes more and more complicated and far removed from a simple schematic dietary plan solely related to the degree of renal impairment [
14]. Nutritional treatment must be increasingly focused and adapted to patient characteristics as well as to clinical and extra-clinical needs. This is in order to obtain the maximum benefits whilst minimizing the risks, as well as to achieve satisfactory patient adherence to dietary prescriptions [
25].
Although the effect on lowering the GFR decline rate seems small [
26,
27], protein restriction appears capable of reducing by 31 % the relative risk of initiating dialysis [
28]. In addition, in patients with ESRD, a low protein regimen can also allow a reduction in the frequency of dialysis [
29‐
31]. Ultimately, these results are of great interest to the patient, nephrologist and health care system alike.