Abstract
Regardless of the primary disease responsible for kidney failure, patients suffering from chronic kidney disease (CKD) have in common multiple impairments of both the innate and adaptive immune systems, the pathophysiology of which has long remained enigmatic. CKD-associated immune dysfunction includes chronic low-grade activation of monocytes and neutrophils, which induces endothelial damage and increases cardiovascular risk. Although innate immune effectors are activated during CKD, their anti-bacterial capacity is impaired, leading to increased susceptibility to extracellular bacterial infections. Finally, CKD patients are also characterized by profound alterations of cellular and humoral adaptive immune responses, which account for an increased risk for malignancies and viral infections. This review summarizes the recent emerging data that link the pathophysiology of CKD-associated immune dysfunctions with the accumulation of microbiota-derived metabolites, including indoxyl sulfate and p-cresyl sulfate, the two best characterized protein-bound uremic retention solutes.
Highlights
Chronic kidney disease (CKD) is defined by abnormalities of kidney function or structure present for more than 3 months
CKD is associated with a complex defect of almost all components of the immune system, resulting in a peculiar state of “chronic inflammatory immune depression” named CKD-associated immune dysfunctions
It is widely accepted that the accumulation of protein-bound retention solutes (PBURS) is a critical factor explaining the dysfunction of innate immunity (Table 2), which accounts for both the increased risk for bacterial infections and the damage to endothelial cells
Summary
Chronic kidney disease (CKD) is defined by abnormalities of kidney function or structure present for more than 3 months. Progress over the last decades has linked these alterations with the accumulation of uremic toxins, i.e., solutes normally excreted by the kidneys, that impair normal cell physiology [3]. In addition to these observations, CKD patients are characterized by a complex impairment of the immune system, which combines low-grade chronic inflammation and the inability to mount protective immune responses. CKD-induced chronic inflammation is associated with a marked increase in cardiovascular mortality [4], while the inability to mount an efficient immune response increases the risk of malignancy [5] and infection [6,7,8]. The pathophysiological mechanisms underlying CKD-associated immune dysfunctions have long remained unclear but recent evidence suggests that the accumulation of certain uremic toxins is responsible for the dysfunction of immune cells
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