Moderate Protein Intake Linked to Lower Dialysis Risk in Nondialysis CKD, 15-Year Study Finds

Chronic kidney disease (CKD) management has been significantly reshaped by newer pharmacological agents, including sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, which have demonstrated meaningful renoprotective and survival benefits.

Despite these advances, patients with CKD stages 3 and 4 continue to experience estimated glomerular filtration rate (eGFR) decline, persistent proteinuria, and elevated cardiovascular risk. Nutritional strategies, particularly the regulation of dietary protein intake, remain substantially underutilized in managing this residual risk.^1,2

Landmark trials such as DAPA-CKD (NCT03036150), EMPA-Kidney (NCT03594110), and FIGARO-DKD (NCT02545049) have reshaped nephrology, yet none reported participants' dietary intake, reflecting a broader oversight in both clinical trials and routine care where nutritional factors are often neglected.^3-5

To address this gap, researchers from Clalit Health Services (CHS) in Israel conducted a 15-year retrospective cohort study evaluating the long-term association between objectively measured dietary protein intake and kidney outcomes. The study was published in JAMA Network Open.¹

Study Design and Patient Population

This retrospective cohort study included adults with CKD stages 3 and 4 who received care within CHS, Israel's largest managed care organization, serving more than 2.1 million individuals. Participants entered the cohort between January 1, 2007, and December 31, 2022, allowing up to 15 years of follow-up. A total of 1441 patients were included in the analysis, with a mean age of about 67.2 years; 35.2% of participants were women.¹

Dietary protein intake (DPI) was assessed using 24-hour urinary nitrogen excretion and normalized to adjusted body weight—referred to as normalized DPI (nDPI)—expressed in grams per kilogram per day. Participants were stratified by an nDPI threshold of 1.0 g/kg/day. The primary composite outcome was time to first occurrence of a 50% or greater eGFR decline, long-term dialysis initiation, or all-cause mortality. All included patients received at least one dietitian consultation with standard counseling on protein restriction at 0.8 g/kg/day.¹

Key Findings: Dialysis Risk and Composite Outcomes

Among the 1441 patients in the full cohort, the median baseline nDPI was about 1.18 g/kg/day, with most patients consuming protein above the recommended dietary allowance of 0.8 g/kg/day. To balance baseline differences between the low-nDPI (<1.0 g/kg/day) and high-nDPI (≥1.0 g/kg/day) groups, propensity score matching was applied, yielding a matched cohort of 530 patients, with 265 per group.¹

In the matched analyses, the lower-nDPI group had a lower risk of the composite outcome (hazard ratio [HR], 0.77; 95% CI, 0.62–0.97), primarily driven by fewer dialysis initiations (HR, 0.65; 95% CI, 0.42–0.99). In adjusted Cox proportional hazard models, the association between lower protein intake and the composite outcome remained significant (HR, 0.75; 95% CI, 0.60-0.93). Directionally consistent but statistically nonsignificant reductions were also observed for 50% eGFR decline and all-cause death. Subgroup analyses demonstrated consistent associations across age, sex, diabetes status, CKD stage, and medication use, with no significant interaction terms.¹

Nutritional Safety and Longitudinal Kidney Function

A central concern with protein restriction in CKD is the risk of nutritional harm, particularly in older or more comorbid patients. The investigators observed no significant between-group differences in nutritional markers, including albumin levels and Geriatric Nutritional Risk Index scores, supporting the safety of moderate protein restriction in this population. Longitudinal eGFR trajectories declined over time in both groups, though the low-NDPI group showed a numerically slower rate of eGFR decline; this difference did not reach statistical significance. The authors noted that these findings align with prior interventional and observational data supporting the feasibility of modest protein restriction when adequate caloric intake is maintained.^1,6,7

Implications for Pharmacy Practice

Pharmacists involved in CKD medication therapy management or ambulatory care are positioned to reinforce dietary protein guidance as a complement to pharmacological therapy. The authors noted that moderate nDPI below 1.0 g/kg/day was associated with reduced risk of dialysis and the composite outcome during long-term follow-up, and that while the risk reduction was smaller than that observed with recent pharmacological interventions such as SGLT-2 inhibitors or mineralocorticoid receptor antagonists, it remains clinically meaningful and highlights the potential role of dietary intervention in addressing residual renal risk.¹

The study also underscored a critical gap in clinical practice: the underuse of 24-hour urinary nitrogen monitoring as an objective tool for assessing dietary protein intake in patients with CKD. Despite being the most accurate noninvasive tool for assessing DPI, its use appears limited, as demonstrated by the proportion of patients excluded due to missing 24-hour urine data, a pattern that likely reflects broader deficiencies in individualized dietary management in CKD care.⁸

For pharmacists, this highlights an opportunity to advocate for more consistent nutritional monitoring as part of a comprehensive CKD care team, while also counseling patients with CKD on the importance of aligning protein intake with guideline-concordant targets.¹

REFERENCES

1. Beberashvili I, Baevsky T, Shmuel D, et al. Protein intake and kidney outcomes in nondialysis chronic kidney disease over 15 years. JAMA Netw Open. 2026;9(4):e269575. doi:10.1001/jamanetworkopen.2026.9575

2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical. 2014;105(4):S117-S314. doi:10.1016/j.kint.2023.10.018

3. Heerspink HJL, Stefansson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446. doi:10.1056/NEJMoa2024816

4. The EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2022;388(2):117-127. doi:10.1056/NEJMoa220423

5. Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385(24):2252-2263. doi:10.1056/NEJMoa21109

6. Piccoli GB, Cederholm T, Avesani CM, et al. Nutritional status and the risk of malnutrition in older adults with chronic kidney disease – implications for low protein intake and nutritional care: A critical review endorsed by ERN-ERA and ESPEN. Clin Nutrition. 2023;42(4):443-457. doi:10.1016/j.clnu.2023.01.018

7. Torreggiani M, Wang AY, Fois A, Piccoli GB. Personalized low-protein diet prescription in CKD population: Merging evidence from randomized trials with observational data. Seminars in Nephrology. 2023;43(2):151402. doi:10.1016/j.semnephrol.2023.151402

8. Cupisti A, Brunori G, Di lorio BR, et al. Nutritional treatment of advanced CKD: twenty consensus. Journ Nephrol. 2018;31(4):457-473. doi:10.1007/s40620-018-0497-z