"Unconditionally Cutting Protein Backfires"... CKD Death Risk Rises 2.2-Fold

Chonnam National University Medical School nephrology team publishes findings in official journal
"Intake should be determined based on each patient's kidney function and nutritional status"

A study has found that when patients with chronic kidney disease (CKD) excessively restrict their protein intake to avoid uremic symptoms, they may need dialysis sooner and face more than twice the risk of death.

A research team from the Division of Nephrology at Chonnam National University Medical School (Professors Seo Sangheon, Ma Seonggwon, and Kim Suwan) said on November 10 that its analysis of data from the Korea National Institute of Health's KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) found that an excessively protein-restricted diet sharply increases the risk of progression to end-stage kidney disease and patient mortality.

The findings have received final approval for publication in JAMA Network Open (impact factor: 11.7), an official journal of the American Medical Association and one of the world's most prestigious medical journals.

Since protein restriction for patients with CKD was established in the late 19th century as a conservative treatment to reduce uremic symptoms, it has been accepted as a standard practice for more than 100 years. However, concerns have persisted in clinical practice that excessive protein restriction can cause protein-energy wasting (PEW), accompanied by malnutrition and muscle wasting, with potentially fatal effects on survival.

The research team conducted a long-term follow-up study of 1,861 nondialysis patients with CKD at nine university hospitals in South Korea over a median of 8.4 years. Instead of relying on patients' subjective survey responses, the researchers used 24-hour urinary urea nitrogen tests to precisely estimate actual protein metabolism in the body, substantially increasing the reliability of the analysis.

The analysis found that, compared with the reference group consuming at least 1.2 g of protein per kilogram of body weight per day, the group on an extremely restricted diet consuming less than 0.6 g/kg per day had a 42% higher risk of progressing to end-stage kidney disease requiring dialysis or a kidney transplant. The risk of death from any cause rose by a striking 117% (about 2.2-fold).

The study has drawn attention for clearly highlighting the limitations of a treatment paradigm that uniformly required patients with CKD to follow low-protein diets. The 2024 clinical practice guidelines of the Kidney Disease: Improving Global Outcomes (KDIGO) organization also recommend that most adults with CKD maintain an appropriate protein intake of about 0.8 g per kilogram of body weight per day. The study is considered key evidence, based on long-term data from Asian patients, demonstrating the importance of maintaining an appropriate intake.

Professor Seo Sangheon of the Division of Nephrology at Chonnam National University, who led the study, said, "We have shown that unconditionally reducing protein intake does not benefit every patient." He added, "These findings are by no means a recommendation for a high-protein diet that could burden kidney function. Appropriate intake should be determined after a comprehensive assessment of each patient's kidney function, nutritional status, and muscle mass."

The study was supported by the KNOW-CKD research project of the Korea Disease Control and Prevention Agency's Korea National Institute of Health (principal investigator: Professor Oh Gukhwan); the Regional Leading Research Center (RLRC) project of the Ministry of Science and ICT and the National Research Foundation of Korea (center director: Professor Kim Suwan); a mid-career researcher grant from the National Research Foundation of Korea (Professor Seo Sangheon); and an academic research project of the Biomedical Research Institute at Hwasun Chonnam National University Hospital (Professor Seo Sangheon).

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