Tailoring Low-Protein Diets to Improve CKD Health Outcomes

Protein restriction has been used as a strategy for delaying disease progression in patients with chronic kidney disease (CKD) for more than 140 years, said the authors of a review article covering research on a low-protein diet in animal models and human patients with CKD.

Despite controversies, they concluded a low-protein diet “remains a valuable recommendation,” as excessive protein intake may lead to glomerular hyperfiltration, accumulation of nitrogenous waste products, and poorer clinical outcomes. They recommended a tailored approach to protein intake recommendations based on individual patient needs to optimize outcomes.

Although high-protein diets are promoted in popular media for weight loss, control of blood glucose, and muscle mass maintenance and growth, long-term high protein intake could have detrimental effects on renal function. The kidneys are “pivotal” in the process of breaking down and excreting proteins, the authors said. Although healthy individuals may not experience adverse effects of a high-protein diet, those with moderately reduced kidney function, those at risk of CKD, or those with CKD “may be more susceptible to harmful effects,” the reviewers said. In these cases, a high-protein diet may lead to an increase in blood levels of toxic metabolites that are typically cleared by healthy kidneys, as well as accelerated progression of CKD.

The US recommended daily allowance (RDA) for protein is currently set at 0.8 g/kg/day for healthy adults. More than 1.5 g protein/kg/day or protein intake exceeding 25% of total calories is considered a high-protein diet, while a low-protein diet, as recommended to patients with CKD, refers to 0.6 g protein/kg/day, 25% lower than the RDA. The authors also commented that the average protein intake among adults in Western countries is much higher than the RDA, approximately 1.3 g/kg/day.

The review discussed several randomized controlled trials and observational studies evaluating a low-protein diet in patients with CKD. Notably, “despite a significant number of epidemiological and clinical trials,” the authors commented that few studies evaluated glomerular filtration rate as an outcome. Some trials have found that a low-protein diet slowed CKD progression, reduced the need for dialysis, increased survival, or improved markers of renal function. Others found no or minimal differences between control and low-protein diet groups; however, poor adherence to the low-protein diet was a limitation in some of these studies.

The authors cited one meta-analysis of 16 randomized controlled trials (RCTs) of protein restriction (less than 0.8 g protein/kg/day) in clinical management of patients with CKD that reported higher serum bicarbonate, lower phosphorus, and a lower rate of progression to kidney replacement therapy, as well as a lower rate of all-cause mortality compared to no protein restriction. Several observational studies also reported that a low-protein diet delayed the progression to kidney replacement. However, another meta-analysis of RCTs found “little or no difference” between a low-protein diet and a normal-protein diet in progression to kidney replacement therapy in patients with stage 3 CKD.

The authors concluded from their review of the literature that although there is no consensus on the effectiveness of a low-protein diet on slowing the progression of CKD, it remains a well‐established strategy for improving health outcomes, with notable benefits on phosphate metabolism, cardiovascular outcomes, intestinal dysbiosis, and metabolic acidosis.

In older adults with CKD, protein requirements may be somewhat higher due to age‐related sarcopenia and changes in protein metabolism. Older adults with CKD not on dialysis may require up to 0.8 g protein/kg/day, “depending on disease progression and nutritional status,” the authors said. Similarly, in critically ill patients, higher protein intake is often considered beneficial, although they noted this has been challenged by recent clinical trials.

A low-protein diet is recommended for non‐dialysis patients with CKD, regardless of whether the protein is derived from animal or plant sources. The reviewers added that consuming predominantly plant protein sources could be beneficial in CKD, as higher intake of dietary fiber could lead to reduced production of uremic toxins through increased synthesis of short‐chain fatty acids and reduced production of toxins by intestinal bacteria.

According to the authors, some clinicians are concerned about patients’ quality of life on a low-protein diet; however, they wrote, “Studies have shown that a decrease in quality of life is related to comorbidities associated with CKD, disease progression, and age, regardless of the amount of dietary protein consumed.” They added that delaying the initiation of dialysis by months or years, as may be achieved by a low-protein diet, is also a major benefit to quality of life. A low-protein diet remains “a fundamental approach to the management of CKD,” and it should be tailored to a patient’s overall health, age, nutritional status, and comorbidities to optimize outcomes, the authors recommended.

Reference

Mafra D, Brum I, Borges NA, Leal VO, Fouque D. Low-protein diet for chronic kidney disease: Evidence, controversies, and practical guidelines. J Intern Med. 2025;298(4):319-335. doi:10.1111/joim.20117