Very Low Protein Intake Tied to Higher Kidney Failure Risk in CKD

Strict dietary protein restriction may do more harm than good for some patients with chronic kidney disease (CKD), according to a prospective cohort study published in JAMA Network Open. Patients with nondialysis CKD whose daily protein intake (DPI) fell below 0.6 g/kg/d had an approximately 42% higher risk of kidney failure requiring replacement therapy (KFRT) and more than double the risk of all-cause mortality compared with those consuming 1.2 g/kg/d or more, a finding pharmacists may want to keep in mind when patients describe aggressive self-directed diet changes.¹

The authors noted that protein restriction has long been a cornerstone of CKD management, but its long-term benefits remain unclear in Asian populations, who often have lower body mass and muscle reserves. A key concern is protein-energy wasting (PEW), a condition highly prevalent in patients with CKD that leads to muscle loss and nutritional imbalance.¹

Study Design

Investigators analyzed data from the Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD), which enrolled patients with CKD stages 1 to predialysis 5 from 9 tertiary hospitals in South Korea between 2011 and 2016. DPI was estimated objectively from 24-hour urinary urea nitrogen excretion at baseline, and participants were grouped into 5 categories, from less than 0.6 g/kg/d to 1.2 g/kg/d or greater. The primary outcome was KFRT, and Fine-Gray models accounted for the competing risk of death.¹

A total of 1861 participants (mean [SD] age, 53.7 [12.0] years) were followed for a median of 9.3 years.¹

Kidney Failure and Mortality Risk

In the fully adjusted model, the lowest DPI group had a significantly higher risk of KFRT than the highest group (subdistribution HR [sHR], 1.42; 95% CI, 1.09-1.85). All-cause mortality was also higher (sHR, 2.17; 95% CI, 1.17-4.03), whereas the risk of major adverse cardiovascular events did not differ significantly across groups. A spline analysis showed a nonlinear association, with KFRT risk increasing sharply as DPI decreased below the cohort median of 0.945 g/kg/d.¹

The association held in sensitivity analyses that excluded participants who reached KFRT within 1 year and those with markers of PEW, such as serum albumin below 3.5 g/dL or total cholesterol below 115 mg/dL. In a propensity score-matched cohort balanced for CKD stage and albuminuria, the lowest DPI group again showed higher KFRT risk (sHR, 1.52; 95% CI, 1.11-2.08). Results were consistent across subgroups, including by diabetes status.¹

How the Findings Fit Current Guidance

Guidance on protein intake in CKD has diverged. The 2020 Kidney Disease Outcomes Quality Initiative nutrition guideline recommends a low-protein diet of 0.55 to 0.60 g/kg/d for metabolically stable adults with CKD stages 3 to 5 without diabetes. The 2024 Kidney Disease: Improving Global Outcomes guideline suggests 0.8 g/kg/d for adults with CKD G3 to G5 and advises avoiding intake above 1.3 g/kg/d in adults with CKD at risk of progression.^2,3 The study authors said their results support this move toward normalized protein intake and argued for individualized dietary management that weighs nutritional status and body composition alongside reducing kidney workload.¹

For pharmacists, the data reinforce the value of asking patients with CKD about their eating habits, particularly those who may be cutting protein on their own. Signs of declining nutritional status warrant referral to a renal dietitian or the patient's nephrology team rather than reinforcement of further restriction.

Limitations

The study was observational and cannot establish causation, and the cohort was entirely Korean, which may limit generalizability. DPI was measured from a single baseline urine collection, total caloric intake and plant versus animal protein sources could not be assessed, and baseline enrollment predated widespread use of kidney-protective agents such as sodium-glucose cotransporter 2 inhibitors.¹

REFERENCES

1. Suh SH, Choi HS, Kim CS, et al; KNOW-CKD Investigators. Low daily protein intake and risk of kidney failure and mortality in chronic kidney disease. JAMA Netw Open. 2026;9(10):e2634568. doi:10.1001/jamanetworkopen.2026.34568

2. Ikizler TA, Burrowes JD, Byham-Gray LD, et al. KDOQI clinical practice guideline for nutrition in CKD: 2020 update. Am J Kidney Dis. 2020;76(3)(suppl 1):S1-S107. doi:10.1053/j.ajkd.2020.05.006

3. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117-S314. doi:10.1016/j.kint.2023.10.018