Study of Oral Uremic Toxin Absorbent and Probiotics to Retard the Progression of Chronic Kidney Disease

CKD

CKD oral absorbent probiotics LncRNA, gut microbiota

In patients with chronic kidney disease (CKD), uremic toxins accumulate when kidney function declines. Those uremic toxins had a greater affinity to circulating proteins are called protein bound uremic toxins, PBUT. Apart from traditional small or middle molecule uremic toxins, the PBUTs can be rarely eliminated using traditional renal replacement therapy, even using high flux dialysis modalities. Among these molecules identified, indoxyl sulfate (IS), and p-cresol (PC) are mostly studied. Both in vitro and in vivo study, IS and PC are associated with endothelial dysfunction, vascular smooth muscle proliferation, and increased risk for CV outcomes. The uremic toxins (IS and PC) are originated in the endogenous environment, mainly from the protein metabolism, food intake, or produced by gut microbiota. Prevention of IS or PC precursors from being absorbed across the intestinal tract has been extensively studied in the renal literature by use of oral adsorbents. In animal models, activated charcoal reduces the serum concentration of creatinine (cre) and may delay CKD progression by alleviating IS overload. An oral form of non-absorbable surface-modified activated bamboo charcoal (ABC), has been demonstrated to effectively reduce circulating and renal IS levels in animal models. Recently, probiotics, prebiotics or synbiotics have been reported to reduce inflammation, improve kidney function and retard progression of CKD by restoring the symbiosis of gut microflora in patients with CKD. A randomized trial found synbiotics decreased serum PCS without reducing serum IS in non-dialysis CKD. Another study found that synbiotics delayed CKD progression. A systematic review found prebiotic and probiotic therapies reduced IS and PCS in patients with end stage kidney disease (ESKD) on haemodialysis. However, it is unclear whether the results hold true for other patients with CKD. Based on these previous findings, investigators will conduct a prospective randomized open blinded end-point (PROBE) study to see if oral uremic toxin absorbent + probiotics prevent CKD progression. Also, a panel of clinical and biochemical profiles will be checked to investigate possible link between several biomarkers and clinical response.

In patients with chronic kidney disease (CKD), uremic toxins accumulate when kidney function declines. Those uremic toxins had a greater affinity to circulating proteins are called protein bound uremic toxins, PBUT. Apart from traditional small or middle molecule uremic toxins, the PBUTs can be rarely eliminated using traditional renal replacement therapy, even using high flux dialysis modalities. Among these molecules identified, indoxyl sulfate (IS), and p-cresol (PC) are mostly studied. Both in vitro and in vivo study, IS and PC are associated with endothelial dysfunction, vascular smooth muscle proliferation, and increased risk for CV outcomes. The uremic toxins (IS and PC) are originated in the endogenous environment, mainly from the protein metabolism, food intake, or produced by gut microbiota. Prevention of IS or PC precursors from being absorbed across the intestinal tract has been extensively studied in the renal literature by use of oral adsorbents. In animal models, activated charcoal reduces the serum concentration of creatinine (cre) and may delay CKD progression by alleviating IS overload. An oral form of non-absorbable surface-modified activated bamboo charcoal (ABC), has been demonstrated to effectively reduce circulating and renal IS levels in animal models. Recently, probiotics, prebiotics or synbiotics have been reported to reduce inflammation, improve kidney function and retard progression of CKD by restoring the symbiosis of gut microflora in patients with CKD. A randomized trial found synbiotics decreased serum PCS without reducing serum IS in non-dialysis CKD. Another study found that synbiotics delayed CKD progression. A systematic review found prebiotic and probiotic therapies reduced IS and PCS in patients with end stage kidney disease (ESKD) on haemodialysis. However, it is unclear whether the results hold true for other patients with CKD. Based on these previous findings, investigators will conduct a prospective randomized open blinded end-point (PROBE) study to see if oral uremic toxin absorbent + probiotics prevent CKD progression. Also, a panel of clinical and biochemical profiles will be checked to investigate possible link between several biomarkers and clinical response. During this 6 months' trial, eligible 120 patients with eGFR 15 \< eGFR \< 45 ml/min/1.73m2 and UACR \> 100 mg/g will be enrolled and randomized into 4 groups. The patients in group 1 will receive CharXenPlus 4g (with ABC 2g) thrice daily + CharXprob 0.8 g once daily in the initial 3 months. Group 2 will receive CharXenPlus 4g thrice daily in the initial 3 months, and CharXprob 0.8 g once daily in the last 3 months. Group 3 will receive CharXprob 0.8 g once daily in the initial 3 months, and CharXenPlus 4g thrice daily in the last 3 months. Group 4 will only receive CharXprob 0.8 g once daily in the last 3 months. In addition to demographic data, the degrees of proteinuria (UACR), serum albumin, AST, ALT, BUN, creatinine, Na, K, Cl, Ca, P, Mg, uric acid, IS, PC, TMAO, FGF-23, klotho, KIM-1, NGAL, metabolomics, lcnRNA, and fecal microbiota will be assessed at the baseline, 3rd and 6th month of the trial.

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