Moderate Diet Change Tied to Renal Benefit in CKD

Moderately restricting protein intake was associated with more favorable kidney outcomes in patients with stage 3 and 4 chronic kidney disease (CKD), an Israeli retrospective study indicated.

Among 530 propensity score-matched adult patients, those with a low versus high normalized dietary protein intake (nDPI) had a 23% lower risk for progression to a composite outcome — 50% or more decline in estimated glomerular filtration rate (eGFR), initiation of long-term dialysis, or all-cause mortality — over a 15-year follow-up (HR 0.77, 95% CI 0.62-0.97, log-rank P=0.03).

This was largely driven by a 35% reduced risk for dialysis initiation (HR 0.65, 95% CI 0.42-0.99), Ilia Beberashvili, MD, of Yitzhak Shamir Medical Center in Zerifin, Israel, and colleagues reported in JAMA Network Open.

There were also trends toward reduced risks for eGFR decline and all-cause death, but associations didn’t reach statistical significance.

“Although the risk reduction was smaller than that observed with recent pharmacologic interventions … it remains clinically meaningful and highlights the potential role of dietary intervention in addressing residual renal risk,” Beberashvili and co-authors noted.

CKD management has advanced greatly with classes of therapies like SGLT2 inhibitors and GLP-1 receptor agonists, they said, but even with pharmacological advancements, CKD patients continue to experience eGFR decline, proteinuria, and high cardiovascular risk.

“Nutritional strategies, particularly regulation of DPI, remain underutilized in addressing this residual risk,” the team pointed out.

The findings back up current guidance that suggests CKD patients limit protein to a target intake of 0.6 to 0.8 g/kg/day so kidneys don’t have to work overtime to remove excess waste. However, prior data about protein restriction on renal outcomes have yielded mixed results, Beberashvili and colleagues highlighted, as some studies supported the practice and others showed no benefit.

Protein reduction can be difficult to achieve in certain patient populations with traditionally high protein consumption, the researchers noted. “Our findings suggest that even moderate protein restriction — rather than strict targets — may still provide meaningful renoprotective benefits,” Beberashvili told MedPage Today.

Patients in the study were categorized into two groups: those with a low nDPI (<1.0 g/kg/day) and those with higher nDPI (≥1.0 g/kg/day). This low threshold reflected a moderately restricted protein intake rather than a "classic low-protein diet" of 0.6 to 0.8 g/kg/day, the authors explained.

“These findings support guideline-based care while emphasizing practicality. Moderate, achievable dietary changes combined with objective monitoring may be more feasible in real-world settings than strict dietary targets,” said Beberashvili. “Further prospective and interventional studies are needed to better define optimal protein intake across different CKD populations.”

The retrospective cohort study included adults with CKD stages 3 or 4 not on dialysis — defined as two eGFR values between 15 to 60 mL/min/1.73 m² — receiving care at a single Israeli center from January 2007 to December 2022. The average patient age was 67 years and 37% were women. About 40% had diabetes and the median Charlson Comorbidity Index score was 5. Roughly 10% were on an SGLT2 inhibitor at baseline and less than 2% were on a GLP-1 agent.

DPI was assessed using 24-hour urinary nitrogen excretion and normalized to adjusted body weight. Median nDPI at baseline was 1.18 g/kg/day.

Low nDPI remained significantly associated with a lower risk for the composite in models adjusted for age, sex, diabetes, body mass index (BMI), eGFR, serum albumin, and urine albumin-to-creatinine ratio or 24-hour proteinuria. Subgroup analyses showed consistent associations across age, sex, ethnic groups, region, diabetes, CKD stage, albuminuria, proteinuria, systolic blood pressure, BMI, and medication use.

While there wasn’t a significant between-group difference, the low nDPI group had a less steep eGFR slope during follow-up. Both groups had comparable increases in albuminuria slopes. No differences in nutritional markers were noted.

The authors acknowledged that because the study concluded in 2022, the low uptake of SGLT2 inhibitors and GLP-1 receptor agonists may limit the generalizability of these findings to current clinical practice.