Abstract
Chronic kidney disease (CKD) is a progressive loss of renal function. The gradual decline in kidney function leads to an accumulation of toxins normally cleared by the kidneys, resulting in uremia. Uremic toxins are classified into three categories: free water-soluble low-molecular-weight solutes, protein-bound solutes, and middle molecules. CKD patients have increased risk of developing cardiovascular disease (CVD), due to an assortment of CKD-specific risk factors. The accumulation of uremic toxins in the circulation and in tissues is associated with the progression of CKD and its co-morbidities, including CVD. Although numerous uremic toxins have been identified to date and many of them are believed to play a role in the progression of CKD and CVD, very few toxins have been extensively studied. The pathophysiological mechanisms of uremic toxins must be investigated further for a better understanding of their roles in disease progression and to develop therapeutic interventions against uremic toxicity. This review discusses the renal and cardiovascular toxicity of uremic toxins indoxyl sulfate, p-cresyl sulfate, hippuric acid, TMAO, ADMA, TNF-α, and IL-6. A focus is also placed on potential therapeutic targets against uremic toxicity.
Highlights
Key Contribution: This review provides an overview of the pathophysiological mechanisms of uremic toxins in the progression of Chronic kidney disease (CKD) and cardiovascular disease (CVD); and describes therapeutic interventions currently being investi-gated for preventing uremic toxin mediated disease progression
Investigations of uremic toxins have generally been investigated independently, despite the fact that many toxins are elevated in the setting of CKD and likely work together in the progression of CKD and CVD
It is important to note that uremic toxins are not the only driver of disease progression in CKD and CVD, and many other factors contribute to disease progression [174]
Summary
Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function present for more than three months [1]. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines classifies CKD into five categories based on glomerular filtration rate (GFR) and three categories based on level of albuminuria, where GFR 30 mg/24 h, or presence of other markers of kidney damage (i.e., electrolyte abnormalities or histological/structural abnormalities) for longer than three months indicates CKD [3]. The loss of kidney function in CKD is progressive and irreversible. Renal replacement therapies, including dialysis and kidney transplantation, are necessary for patients who progress into end stage renal disease (ESRD; GFR
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