Abstract

ENZOBIOTICS IN ADVANCED CHRONIC KIDNEY DISEASE A DOUBLE BLIND RANDOMIZED CONTROL TRIAL –SUB ANALYSIS OF EETOX STUDY

Sanjay Srinivasa*, Ilangovan Veerappan, Amit Gupta, Chakko Jacob, Amol Mahaldar and Ananthasubramaniam Rajagopal

ABSTRACT

Dysbiosis in chronic kidney disease (CKD) results in elevated levels of protein-bound uremic toxins (PBUTs), which contribute to insulin resistance, renal function decrease, and cardiovascular disease risk. Enzobiotics, a combination of synbiotics and proteolytic enzymes, are intended to restore gut homeostasis and lower PBUTs in patients with CKD. This subanalysis of the EETOX trial investigates the therapeutic efficacy of Enzobiotics in attenuating plasma concentrations of protein-bound uremic toxins—specifically p-Cresol Sulfate (PCS) and Indoxyl Sulfate (IS)—while preserving residual renal function in patients with advanced chronic kidney disease (CKD). The PCS and IS were not in standard guideline and require advance lab requirement and this trial investigates PCS and IS in advance stage of CKD. Methods: A randomized, double-blind, placebo-controlled clinical trialwas conducted involving 46 patients with stage 4 or 5 CKD. Participants were randomized to receive either Enzobiotics or placebo, and biochemical parameters including PCS, IS, serum creatinine, blood urea nitrogen (BUN), serum potassium, and estimated glomerular filtration rate (eGFR) were assessed at baseline (day0) and after 90 days of intervention. Results: The Enzobiotics-treated group demonstrated an 18% reduction in Indoxyl sulfate (IS) concentrations, whereas the placebo group exhibited a 52% increase (p < 0.01). Additionally, p-Cresol Sulfate (PCS) levels decreased by 35% in the Enzobiotics group, in contrast to a modest 10% reduction observed in the placebo group (p < 0.01). Enzobiotics therapy also slowed the rate of urea increase (1% vs. 8%), stabilized creatinine levels, reduced potassium by 2%, and slowed eGFR decline (8% vs. 13%, p < 0.01). Conclusion: Enzobiotics significantly lowers levels of protein-bound uremic toxins (PBUTs) and contributes to the preservation of renal function in patients with advanced chronic kidney disease. Through its anti-inflammatory effects and stabilization of key renal biomarkers, Enzobiotics represents a potential therapeutic strategy to slow CKD progression and defer the initiation of dialysis.

Keywords: Enzobiotics, p-Cresol Sulfate, Indoxyl Sulfate, Stage 4 & 5 CKD, Creatinine, Urea.