The quest for a better understanding of chronic kidney disease complications: an update on uremic toxins

Abstract

Chronic kidney disease is characterized by a progressive reduction of glomerular filtration rate and/or the appearance of proteinuria, and subsequently the progressive retention of organic waste compounds called uremic toxins (UT). Over the last decades, a large number of such compounds have been identified and their effects on organs and tissues, especially the cardiovascular system, has been demonstrated. In this review, we present the current classification of UT, as proposed by the EUTox Group, and the effects of some of the probably most important UTs, such as phosphate, FGF-23, PTH, AGEs, indoxyl sulfate and para-cresyl sulfate. We provide an overview on therapeutic approaches aimed to increase their extracorporeal removal via convective and/or adsorptive strategies and to lower their intestinal production/ absorption via dietetic and pharmacological interventions. The recognition that multiple toxins contribute to the uremia supports the need for new therapeutic targets, with a potentially positive impact on CKD progression and survival.

The Rise of Expanded Hemodialysis

“…The complex story of uremia is slowly but progressively unfolding, thanks to the contribution of several investigators [17]. New retention molecules considered responsible for specific clinical outcome have been identified.…”

Sacran, a High-molecular Weight Polysaccharide Inhibits Renal Injury and Oxidative Stress in Chronic Renal Failure Model Rats

“…It is also present at high levels in the serum of patients with CRF, and appears to be involved in the progression of CRF and the onset of complications associated with it. In fact, recent clinical studies have demonstrated that the serum levels of indoxyl sulfate are a powerful predictor of overall and cardiovascular mortality, and that it has an inverse relationship with renal function and a direct relationship with aortic calcification and pulse wave velocity [3,4]. In addition, several groups have reported that indoxyl sulfate has the potential to produce oxidative stress, a situation that is accompanied by the production of excess levels of reactive oxygen species (ROS) in renal tubular cells, mesangial cells, aortic smooth muscle cells and vascular endothelial cells [5,6].These actions are mediated by the intracellular uptake of indoxyl sulfate via the organic anion transporter 1 (OAT1) and/or OAT3 [7].…”

Role of Organic Anion Transporters in the Uptake of Protein-Bound Uremic Toxins by Human Endothelial Cells and Monocyte Chemoattractant Protein-1 Expression

“…IS is derived from dietary tryptophan, which is metabolized to indole by intestinal bacteria and, after being absorbed by the intestine, passes through the bloodstream and reaches the liver, where it undergoes sulfation and gets converted to IS. These toxins are excreted through the kidney proximal tubule and accumulate in the blood of patients with renal function impairment [13]. …”

“…IS is normally excreted in the urine, with an average rate of excretion ranging from 50-70 mg/day in healthy persons [13]. Approximately 90% of IS present in uremic patients is bound to human serum albumin [18].…”