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

Patients with nondialysis chronic kidney disease (CKD) whose estimated daily protein intake (DPI) fell below 0.6 grams of protein per kilogram of body weight per day (g/kg/d) had a higher risk of progressing to kidney failure and of dying than those with the highest intake, according to a cohort study published in JAMA Network Open.¹

“In this cohort study of 1861 patients with nondialysis CKD, low protein intake was not associated with significant nephroprotection and was associated with a higher risk of KFRT [kidney failure with replacement therapy] and all-cause mortality,” wrote the researchers of the study. “These findings suggest that rigid protein restriction should be balanced with nutritional monitoring to prevent protein-energy wasting, particularly in populations with lower muscle mass, and a more individualized approach to dietary protein management in CKD may be warranted.”

Protein restriction has long been a cornerstone of conservative CKD care, on the rationale that dietary protein generates uremic toxins and metabolic acidosis that drive intraglomerular hypertension and kidney injury. Current guidance has moved toward a more moderate target. The Kidney Disease: Improving Global Outcomes (KDIGO) 2024 guideline suggests a protein intake of 0.8 g/kg/d for adults with CKD stages G3 to G5 and, as a practice point, advises against intake above 1.3 g/kg/d in adults at risk of progression.² For a 68-kg (about 150-lb) adult, that 0.8 g/kg/d target works out to roughly 54 g of protein per day.

Lowest Protein Group Faced Higher Risk of Kidney Failure and Death

The researchers analyzed 1861 participants from the Korean Cohort Study for Outcomes in Patients With CKD (KNOW-CKD), which enrolled patients with CKD stages 1 to predialysis 5 from 9 tertiary hospitals in South Korea between 2011 and 2016.¹ DPI was estimated from 24-hour urinary nitrogen excretion at baseline, and patients were grouped into 5 categories: less than 0.6 g/kg/d (n = 132), 0.6 to less than 0.8 (n = 403), 0.8 to less than 1.0 (n = 555), 1.0 to less than 1.2 (n = 406), and 1.2 g/kg/d or greater (n = 365), the reference group. Mean age was 53.7 years, and median follow-up was 9.3 years.

During follow-up, 726 participants progressed to kidney failure with replacement therapy (KFRT). KFRT occurred in 61 of 132 patients (46.2%) in the lowest intake group vs 93 of 365 (25.5%) in the highest. In the fully adjusted model, the lowest intake group had a significantly higher risk of KFRT (subdistribution HR [sHR], 1.42; 95% CI, 1.09-1.85; P = .01).

All-cause mortality was also higher in the lowest intake group: 23 of 132 patients (17.4%) died vs 33 of 365 (9.0%) in the highest group (sHR, 2.17; 95% CI, 1.17-4.03; P = .01). Rates of major adverse cardiovascular events did not differ significantly across groups.

The relationship was nonlinear, with KFRT risk rising sharply as DPI dropped below the reference median. At baseline, patients in the lowest intake group tended to have lower serum albumin, hemoglobin, and estimated glomerular filtration rate, and diabetes was more common in that group.

Results Held Across Sensitivity and Subgroup Analyses

The link between low intake and KFRT persisted after the researchers excluded patients who reached KFRT within the first year, as well as those with markers of potential protein-energy wasting (serum albumin < 3.5 g/dL or total cholesterol < 115 mg/dL). It also held after adjustment for echocardiographic parameters and in a propensity score–matched cohort balanced for CKD stage and albuminuria (sHR, 1.52; 95% CI, 1.11-2.08). The association was consistent across subgroups, including by diabetes status (P for interaction = .35).

The authors wrote that their results support KDIGO's shift toward normalizing protein intake and suggest that the risks of the traditional 0.6 g/kg/d threshold may outweigh its marginal benefits, particularly in Asian populations. They suggested the excess risk likely reflects protein-energy wasting and sarcopenia, conditions to which Asian populations with lower body mass index and muscle reserves are particularly vulnerable.

Because the study was observational, it cannot establish causation, and residual confounding cannot be ruled out. All participants were Korean; the researchers could not adjust for total caloric intake or distinguish animal from plant protein, and data on newer kidney-protective agents such as SGLT2 inhibitors were unavailable.

“Our findings challenge the one-size-fits-all application of strict low-protein diets across all ethnic groups,” wrote the researchers. “From a clinical perspective, nephrologists should prioritize the preservation of nutritional status and muscle mass alongside kidney workload reduction. Future guidelines should incorporate more nuanced, individualized dietary recommendations that consider the patient’s nutritional integrity and body composition to optimize long-term survival and kidney outcomes.”

References

1. Suh SH, Choi HS, Kim CS, et al. 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. 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