Study Questions Safety of Strict Protein Restriction in Chronic Kidney Disease

— Consuming less than 0.6 g/kg a day correlated with higher risks of kidney failure, death

DENVER -- Strict dietary protein restriction was associated with worse clinical outcomes in patients with chronic kidney disease (CKD) who were not dependent on dialysis, a South Korean prospective cohort study suggested.

Compared with patients consuming the highest amount of daily protein (≥1.2 g/kg), those consuming the least (<0.6 g/kg) had a 42% greater risk of kidney failure requiring long-term maintenance hemodialysis, peritoneal dialysis, or kidney transplantation (subdistribution hazard ratio [sHR] 1.42, 95% CI 1.09-1.85).

As for secondary endpoints, the lowest protein intake category was associated with more than double the risk of all-cause mortality (sHR 2.17, 95% CI 1.17-4.03), though was not linked to more major adverse cardiovascular events, Soo Wan Kim, MD, PhD, of Chonnam National University Medical School in Gwangju, South Korea, and colleagues reported in JAMA Network Openopens in a new tab or window.

The findings were simultaneously presented at the American Society of Nephrology Kidney Weekopens in a new tab or window annual meeting.

The authors noted that "maintaining adequate nutritional status and preventing protein-energy wasting may be as critical as reducing the kidney workload," emphasizing that nephrologists should prioritize preserving nutritional status and muscle mass alongside workload reduction.

In 2024, KDIGO guidelinesopens in a new tab or window shifted toward a more moderate protein intake for CKD, departing from prior guidance favoring thresholds near 0.6 g/kg per day. For CKD stages 3-5, guidelines now recommend approximately 0.8 g/kg a day, which the authors noted is "a level consistent with the recommended daily allowance for the general population."

The biological rationale for protein restriction "is centered on the premise that protein intake serves as a primary source of uremic toxins and metabolic acidosis, which together drive intraglomerular hypertension and accelerate the progression of kidney injury," Kim's team explained.

"Our findings provide robust longitudinal evidence to support this normalization of protein intake," they added, and suggest that risks of the traditional 0.6 g/kg per day threshold "may outweigh the marginal benefits of kidney workload reduction."

George Bonifant, MD, training program director for the nephrology fellowship at Northwell Staten Island University Hospital in New York City, who was not involved with the study, noted that while clinicians have prescribed low-protein diets for decades, "this strict advice has been debated."

"We typically try to focus on kidney patients' body weight and provide a recommendation in terms of mg of the amount of protein they should be eating every day," he said. "Classically, we have recommended anywhere from 60-80% of their total body weight in kg in terms of the mg of proteins that they should take in," which is usually "how much fits in the palm of your hand."

Patients who keep daily protein intake below 0.6 g/kg face substantial risks of protein-energy wasting, Bonifant warned. This condition is detrimental because patients enter "more of a catabolic state," he told MedPage Today. "In terms of muscle loss, the products that start accumulating in the bloodstream as a result of increased protein muscle metabolism, like urea nitrogen and hydrogen ion, can be detrimental to kidney health and accelerate kidney failure."

These metabolites generate oxygen free radicals, Bonifant said, and "lead to increased scarring or fibrosis of the tubules of your kidney, and they can lead to accelerated kidney failure just by virtue of you just not eating enough protein to begin with."

He suggested CKD patients consider plant-based protein over animal sources, as plant protein profiles can be gentler on renal hemodynamics, while curtailing foods high in saturated fat, cholesterol, and refined sugars.

For the KNOW-CKD study, investigators analyzed 1,861 ethnically Korean patients with CKD stages 1 to predialysis 5 across nine tertiary hospitals from 2011 to 2016, following them for a median of 9.3 years. Mean participant age was 53.7 years, and 60.6% were male. Daily protein intake was objectively estimated using baseline 24-hour urinary urea nitrogen excretion.

Participants in the lowest daily protein intake category tended to have higher body mass index and systolic blood pressure, alongside lower baseline serum albumin, hemoglobin, and estimated glomerular filtration rates. Diabetes was also more prevalent in this group.

The link between severe protein restriction and kidney failure requiring replacement therapy held across sensitivity analyses, such as excluding patients reaching that stage within 1 year or those with protein-energy wasting markers (albumin <3.5 g/dL or cholesterol <115 mg/dL) and adjusting for echocardiographic parameters.

Because the study was observational, causality could not be definitively established, the authors acknowledged. Other limitations included lack of adjustment for total caloric intake, lack of differentiation between plant and animal protein, and reliance on a single baseline urine collection.