Clinical Question

In patients without diabetes mellitus who have chronic kidney disease (CKD), is a low-protein diet effective at preventing progression to end-stage renal disease (ESRD) or the need for dialysis?

Evidence-Based Answer

There is moderate-quality evidence that compared with low-protein diets (0.5 to 0.6 g per kg per day) or normal-protein diets (0.8 g per kg per day or more), very low-protein diets (0.3 to 0.4 g per kg per day) reduce the number of patients with advanced kidney disease (CKD stage 4 or 5) who progress to ESRD (i.e., the need for dialysis or transplant; relative risk [RR] = 0.65; 95% CI, 0.49 to 0.85). However, in patients with less advanced disease (CKD stage 3 or lower), low-protein diets do not appear to reduce the progression to ESRD compared with normal-protein diets (RR = 1.05; 95% CI, 0.73 to 1.53; low-certainty evidence).¹ (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

CKD is defined as abnormalities of the structure or function of the kidneys present for three months or more, often diagnosed initially by a glomerular filtration rate of less than 60 mL per minute per 1.73 m^2.2 In 2016, an estimated 37 million adults in the United States had CKD, representing 15% of all U.S. adults.³ CKD is associated with a number of adverse health outcomes, including increased all-cause and cardiovascular-related mortality.² Identifying interventions that may halt the progression of CKD to ESRD may lead to improved clinical outcomes and lower costs. Protein-restricted diets are thought to have nutritional benefits in patients with CKD, particularly in correcting metabolic acidosis and reducing the adverse effects of phosphate and sodium retention. This Cochrane review aimed to investigate whether low-protein or very low-protein diets were effective in preventing the progression of CKD and delaying the need for dialysis and/or transplant.¹

This updated review included 17 randomized and quasi-randomized controlled trials.¹ The total number of participants was 2,996 adults without diabetes who had moderate to severe CKD (stage 3 or higher). Participants were 15 to 75 years of age, and the study duration ranged from 12 to 50 months. The review found no difference in the number of patients reaching ESRD when comparing a low-protein diet with a normal-protein diet (RR = 1.05; 95% CI, 0.73 to 1.53; low-certainty evidence). However, when comparing a very low-protein diet to a normal- or low-protein diet, there appeared to be moderate-quality evidence demonstrating a reduction in the number of people reaching ESRD (RR = 0.65; 95% CI, 0.49 to 0.85). It was unclear whether very low-protein diets impacted or changed the glomerular filtration rate compared with normal- or low-protein diets (very low-certainty evidence). There were no significant differences in death rates among participants who followed a low-protein diet (five studies, 1,680 participants; RR = 0.77; 95% CI, 0.51 to 1.18) or very low-protein diet (six studies, 681 participants; RR = 1.26; 95% CI, 0.62 to 2.54).

Adherence to the protein-restrictive diet was measured at regular intervals in all studies and largely reported to be satisfactory. However, no study formally assessed the impact of the dietary restriction on quality of life. Data on adverse effects were limited. Three studies reported that body weight declined during the first few months of the low-protein diet, but then stabilized. Of the 15 studies that assessed for protein energy wasting (malnutrition), 12 found no evidence of malnutrition, and three showed small amounts of wasting.

Current clinical guidelines do not support restricting protein intake to less than 0.8 g per kg per day, the recommended daily intake for the general population, as part of standard treatment to slow the progression of CKD.^2,4 Further studies are needed to better understand the potential benefits of reduced protein intake, as well as adverse effects and impact on quality of life. A 2009 Cochrane review found that very low- or low-protein diets reduced the composite outcome of death and ESRD.⁵ This review provides low- to moderate-certainty evidence that for patients with advanced CKD, clinicians should assess dietary protein intake and engage in shared decision-making regarding dietary protein restriction.

The practice recommendations in this activity are available at http://www.cochrane.org/CD001892.