Effects of a Plant-Dominant Protein Diet on Uremic Toxins and Gut Microbiota in Patients with CKD: The PLANT-CKD Trial

Background: Plant-dominant protein diets, characterized by a higher proportion of plant-based proteins relative to animal-based proteins, may mitigate various chronic kidney disease (CKD)-related metabolic disturbances including uremia and dysbiosis. However, evidence regarding their efficacy in patients with advanced CKD remains limited. Methods: The PLANT-CKD study was an open-label, single-center, randomized controlled trial enrolling 40 Japanese patients with an estimated glomerular filtration rate (eGFR) <20 mL/min/1.73m2 and serum potassium levels <5.5 mEq/L who were receiving renin-angiotensin system inhibitors. Patients were randomized to receive pre-prepared diets containing either 70% (plant-protein group) or 50% (control group) of total protein from plant sources for four weeks. The primary outcome was the changes in serum uremic toxin levels, including indoxyl sulfate (IS), p-cresyl sulfate (PCS), and trimethylamine N-oxide (TMAO). Results: A total of 36 patients were randomized (n=18 in each group). The median [interquartile range] eGFR was 13 [10, 17] mL/min/1.73m2. After 4 weeks, 34 patients (94%) reported good adherence to the study diets. Serum TMAO levels significantly decreased in the plant-protein group compared with those in the control group (between-group difference [95% confidence interval] -2.7 [-4.5, -0.9] μg/mL; false discovery rate [FDR]-adjusted P=0.009), whereas no significant between-group differences were observed for IS (-0.7 [-2.5, 1.0] μg/mL; FDR-adjusted P=0.6) or PCS (-1.2 [-5.4, 3.0] μg/mL; FDR-adjusted P=0.6). Additionally, the plant-protein group showed higher venous bicarbonate levels (between-group difference 2.0 [0.3, 3.6] mEq/L) and serum acetate levels, the predominant short-chain fatty acid (between-group difference 0.3 [0, 0.6] μg/mL). Moreover, the fecal abundance of Bilophila, a pro-inflammatory genus, significantly decreased, whereas the abundance of Butyricicoccus, a butyrate-producing genus, significantly increased in the plant-protein group compared with the control group. Changes in serum potassium levels did not differ significantly between groups. Conclusion: A plant-dominant protein diet reduced serum TMAO levels and modulated gut microbiota in patients with advanced CKD.