Regulation and function of CX3CR1 and its ligand CX3CL1 in kidney disease

Attraction, retention, and differentiation of leukocytes to and within the kidney are governed by chemokines. The chemokine CX3CL1 (fractalkine) and its receptor CX3CR1 are exemplary in this regard as they are highly expressed and further upregulated in a range of kidney diseases. CX3CL1 is chiefly produced by renal endothelium and tubular epithelium, where it promotes leukocyte attraction. Recent data suggest that in addition to established soluble mediators, cellular interactions may enhance CX3CL1 expression. The receptor CX3CR1 is essential in myeloid phagocyte homing to the kidney at homeostasis, after acute cell depletion and in inflammation. CX3CR1 and its ligand are highly regulated in human kidney diseases such as IgA nephritis, systemic lupus erythematosus, and inflammatory conditions such as transplant rejection. A mechanistic role of CX3CR1 has been established in experimental models of nephrotoxic nephritis and renal candidiasis. It is debated in fibrosis. Recent publications demonstrate a role for CX3CR1+ myeloid cells in radio-contrast-agent and sepsis-induced kidney damage. Systemically, circulating CX3CR1+ monocytes reversibly increase in individuals with renal impairment and correlate with their cardiovascular risk. In this review, we discuss role and regulatory mechanisms of the CX3CL1-CX3CR1 axis in both localized and systemic effects of renal inflammation.

Fungal infections of the kidney and those associated with renal failure, dialysis, and renal transplantation

Fungal infections involving the kidney are often a manifestation of disseminated fungal infection, although primary renal fungal infections do occur, usually from a lower urinary tract source or in the setting of renal transplantation. Candida spp. cause the vast majority of these infections and are the representative pathogen for understanding the pathogenesis of these types of infections. The risk factors and mycology of acute renal candidiasis reflect those of invasive candidiasis. Unique risk factors are observed in chronic renal candidiasis, which manifests differently and requires distinct management approaches. This chapter discusses the spectrum of invasive mycoses involving the kidney, as well as those associated with chronic renal failure, dialysis, and renal transplantation.