(1) School of Medicine, University of Queensland, Australia
(2) Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
(3) Translational Research Institute, Brisbane, Queensland, Australia
*Corresponding author Email:
Over the past decade, indoxyl sulphate and p-cresyl sulphate have emerged as potentially important, therapeutically modifiable, toxins in patients with chronic kidney disease. Both are protein-bound uremic retention solutes that are generated from colonic bacterial fermentation of dietary protein and have been associated with cardiovascular disease, kidney disease progression and overall mortality in the chronic kidney disease population. This review provides an overview of the toxicokinetics and nephrovascular toxicity of indoxyl sulphate and p-cresyl sulphate and then focuses specifically on the strengths and weakness of proposed therapeutic opportunities for targeting these molecules, including inhibition of colonic bacterial biosynthesis (protein restriction and preand pro-biotic therapy), suppression of absorption (oral adsorbents), augmentation of clearance (enhanced dialysis) and modulation of cellular pathways (organic anion transporters and antioxidants).
The uremic retention solutes, indoxyl sulphate and p-cresyl sulphate, have been identified as potentially important nephrovascular toxins that are highly amenable to therapeutic manipulation. In particular, targeting biosynthesis through preand pro-biotic therapy holds great potential as a tolerable, targeted and cost-efficient therapy for reducing serum concentrations of indoxyl sulphate and p-cresyl sulphate in the clinical setting. Well-designed clinical trials in the chronic kidney disease population are warranted to investigate whether reductions in indoxyl sulphate and p-cresyl translate into improved cardiovascular outcomes.