Health & Medical Kidney & Urinary System

Vegetarian Low-Protein Diets Supplemented With Keto Analogues

Vegetarian Low-Protein Diets Supplemented With Keto Analogues

Abstract and Introduction


Background. Low-protein diets are often mentioned but seldom used to slow chronic kidney disease (CKD) progression. The aim of the study was to investigate the potential for implementation of a simplified low-protein diet supplemented with alpha-keto analogues (LPD-KA) as part of the routine work-up in CKD patients.

Methods. In an implementation study (December 2007–November 2011), all patients with CKD Stages IV–V not on dialysis, rapidly progressive Stage III and/or refractory proteinuria, were offered either a simplified LPD-KA, or commercially available low-protein food. LPD-KA consisted of proteins 0.6 g/kg/day, supplementation with Ketosteril 1 pill/10 Kg, 1–3 free-choice meals/week and a simplified schema based on 'allowed' and 'forbidden' foods. 'Success' was defined as at least 6 months on LPD-KA. Progression was defined as reduction in glomerular filtration rate (GFR)[(Chronic Kidney Disease Epidemiology Collaboration) formula CKD-EPI] in patients with at least 6 months of follow-up.

Results. Of about 2500 patients referred (8% CKD Stages IV–V), 139 started LPD-KA; median age (70 years) and prevalence of comorbidity (79%) were in line with the dialysis population. Start of dialysis was the main reason for discontinuation (40 cases, unplanned in 7); clinical reasons were recorded in 7, personal preference in 14 and improvement and death in 8 each. The low gross mortality (4% per year) and the progression rate (from −8 to 0 mL/min/year at 6 months) are reassuring concerning safety. None of the baseline conditions, including age, educational level, comorbidity or kidney function, discriminated the patients who followed the diet for at least 6 months.

Conclusions. Our data suggest a wider offer of LPD-KA to patients with severe and progressive CKD. The promising results in terms of mortality and progression need confirmation with different study designs.


Chronic kidney disease (CKD) is a major health care problem, and retarding its evolution to end-stage renal disease (ESRD) has obvious clinical and economic implications. The first attempts to modulate kidney function via the diet date back to over a century ago, and the systematic studies of Thomas Addis, on which low-protein diets are still extensively based, were published over 60 years ago. In spite of several trials conducted during the last decade, the role of low-protein diets remains controversial with discrepancies between results in intention-to-treat analysis and those in per-protocol analysis. However, it is now usually held that the effect of a low-protein diet on the progression of CKD becomes evident only when protein intake is <0.8 g of proteins/kg/day. Milder regimens may have an effect as 'metabolic stabilizers', a new concept that underlines the clinical and economical advantages of even relatively small 'gains' in a pre-dialysis phase.

A regimen with 0.6 g/kg/day of proteins is often difficult, unless either a vegan diet (usually supplemented with essential amino acids and keto acids) is proposed or 'non-proteic' (commercially available) carbohydrates are employed; the combination of both approaches allows protein intakes as low as 0.3 g/kg/day. In spite of these problems, a few fundamental systematic reviews have concluded that the experience with low-protein diets is generally positive, at least in selected settings.

However, low-protein diets are still under-employed and the main concerns regard their safety and implementation in clinical practice. The comment appearing in The Lancet almost 30 years ago still holds true: 'The practical implications of these ideas are enormous, but the time is not yet ripe for generalized, uncontrolled, application of restricted and unpleasant diets to patients with renal disease'. Indeed, several barriers hinder the application of low-protein diets in CKD patients: they are often 'unpleasant and restricted', impairing long-term compliance; they are difficult to study and they are rather expensive if they employ 'non-proteic' commercial food or keto-acid supplementation.

Nevertheless, at least three main reasons suggest that the time is 'ripe' for a systematic integration of diet in the clinical treatment of CKD: the cost of dialysis, the clinical advantages and the failure of early dialysis to prolong survival. The global world crisis is challenging all health care systems, and the high costs of dialysis are central to cost containment. Recent studies suggest that the 'early dialysis' approaches do not add to survival, thus underlining the advantages of low-protein diets not only in slowing the progression of renal failure, but also as metabolic stabilizers, allowing prolongation of the 'pre-dialysis phase' and ensuring equivalent survival at lower costs.

Therefore, the present study was designed to investigate the potential for implementation of a simplified approach to a low-protein diet supplemented with alpha-keto analogues (LPD-KA), with a protein intake of 0.6 g/kg/day, as part of the routine clinical work-up in non-selected populations of CKD patients. The study was aimed at answering the question whether it was possible to identify a profile of 'ideal patients' to be prescribed an LPD-KA diet, in keeping with the suggestions in the literature (young, educated and compliant); the absence of a specific profile would suggest offering a diet trial to all CKD patients willing to try it.

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