Normoproteic Plant-Dominant Protein Diets, Uremic Toxins, and Gut Microbiota in Patients With Advanced CKD: A Randomized Controlled Trial

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• Picked for Nephrology (top studies of the week, 27 September 2026): RCT shows diet impacts uremic toxins in advanced CKD

Abstract

RATIONALE & OBJECTIVE: Plant-dominant protein diets may ameliorate metabolic disturbances associated with CKD, such as uremia and gut microbiota dysbiosis, although interventional evidence remains limited. This trial investigated their effects on uremic toxins and other metabolic disorders in patients with advanced CKD. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: 36 Japanese patients with an eGFR <20 mL/min/1.73m2 and serum potassium levels <5.5 mEq/L, who received renin-angiotensin system inhibitors. INTERVENTION: Patients were randomly assigned to receive pre-prepared normoproteic (0.8 g/kg/day) diets in which 70% (plant-protein diet group) or 50% (control group) of total protein was derived from plant sources for 4 weeks. OUTCOMES: The co-primary outcomes were serum indoxyl sulfate (IS), p-cresyl sulfate (PCS), and trimethylamine N-oxide (TMAO). Secondary outcomes included venous bicarbonate, serum short-chain fatty acids (SCFAs), and 16S rRNA sequencing of fecal microbiota. RESULTS: Thirty-six patients were randomized (18 per group). Their median (interquartile range) eGFR was 13 (10, 17) mL/min/1.73m2, and 55% were female. After four weeks, 34 patients (94%) reported good adherence to the study diets. Serum TMAO levels were significantly reduced in the 70% plant-protein diet group compared to the control group (between-group difference [95% confidence interval] -4.6 [-7.2, -2.0] μg/mL; false discovery rate [FDR]-adjusted P=0.003), whereas no significant between-group differences were observed for IS (-0.8 [-2.5, 0.9] μg/mL; FDR-adjusted P=0.5) or PCS (-0.9 [-5.1, 3.4] μg/mL; FDR-adjusted P=0.7). The plant-protein diet increased venous bicarbonate, serum calcium, and serum acetate, while reducing parathyroid hormone. Pro-inflammatory gut microbiota genera decreased, while SCFA-producing genera increased with the plant-protein diet. Changes in serum potassium did not differ significantly between groups. LIMITATIONS: Small sample size and short intervention period. CONCLUSION: A normoproteic 70% plant-protein diet reduced TMAO, favorably modulated gut microbiota, and did not cause an increase in serum potassium in patients with far-advanced CKD. FUNDING: Grants from government (Osaka Kidney Foundation and Japan Society for the Promotion of Science) and not-for-profit (Osaka Heart Club) sources.

Abstract as published, via PubMed.