The Effect of Probiotics vs Activated Charcoal in the Management of CKD Patients Suffering From Uremic Pruritus.

Chronic kidney disease-associated pruritus (CKD-aP) , also called uremic pruritus (UP) is a critical problem defined as un pleasant sensation that desire to itch and scratch experienced by people with chronic kidney disease (CKD) patients . Pruritus is the most common skin symptoms related with uremia and has a major clinical effect being associated strongly with poor quality of life , impaired sleep and increased mortality, so it's important to explore an efficient treatment option for it. Although the pathogenesis of pruritus remains largely unclear, it is demonstrated that pruritus is mainly ascribed to the retention of uremic solutes.

Gut microbiome has gained attention and is increasingly noted to play a significant role in a number of disorders including CKD. Patients with CKD can be characterized with lower bacterial richness and diversity. Like the gut, human skin has its own microbiome. Recent study showed that CKD patients with pruritus had a different bacterial community comparing to those without pruritus indicating that altered skin microbiome associated with pruritus in patients with CKD and also with accumulation of uremic toxins in skin. So, the skin microbiome plays a potential role in regulating the skin symptoms in CKD patients. Therefore, these findings might be useful for making probiotics supplements to relieve patient's skin symptoms or renal damage.

Indoxyl sulfate (IS) is one of the most potent protein bound uremic toxins derived from the gut microbes. IS is generated by bacterial metabolism of trptophan to indole. The serum IS was significantly elevated in patients with CKD associated pruritus. Moreover, High serum IS concentration has a strong relationship with pruritus severity and a negative impact on quality of life. Therefore, IS may represent a potential therapeutic target to reduce the pruritus severity.

To decrease serum IS levels either decrease IS production by using probiotic supplementation or decrease IS intestinal absorption by addition of activated charcoal as an adsorbent agent has been evaluated in uremic patients.

Probiotics are defined as live microorganisms that consumed in adequate amounts; confer a health effect on the host. Probiotics supplement regulating the immune system and improving the skin barrier. Probiotics work by competing with pathogenic organisms for nutrients, which prevent the growth of harmful bacteria. So, probiotics has a key role in improving the microbiota.Several clinical trials are being carried out on the efficacy of probiotics for the treatment of many skin problems. Some trials also showed that probiotics has a role in reducing of protein bound uremic toxin such indoxyl sulfate (IS).We hope that this study forms a contribution to promoting probiotics as a novel therapeutic approach for the treatment of uremic pruritus.

Activated charcoal is a powerful, intestinal adsorbent within the gastrointestinal (GI) tract, effectively trapping various chemicals. These captured substances are then retained within the charcoal matrix, preventing or reducing their absorption into the blood stream. Activated charcoal has been found to effectively eliminate urea and other uremic toxin such as indoxyl sulfate due to its ability to bind with IS and expelling it through feces. It's also showed that the usage of activated charcoal resulted in decreasing pruritus severity and improving the quality of life of patients without serious side effects.

• Evaluation of the safety of probiotics supplementation and activated charcoal in patients with uremic pruritus. [Time frame: Four weeks]