Background: Chronic renal disease (CKD) is characterized by complex changes in cell metabolism leading to an increased production of oxygen radicals, that, in turn has been suggested to play a key role in numerous clinical complications of this pathological condition. Several reports have focused on the identification of biological elements involved in the development of systemic biochemical alterations in CKD, but this abundant literature results fragmented and not exhaustive.

Clinical relevance of cytokine production in hemodialysis.ates a complex of acute and chronic side effects also Blood-dialyzer interaction in hemodialysis has the potential known as "bioincompatibility phenomena" [4, 5].to activate mononuclear cells leading to the production of Many aspects regarding morbidity and mortality of inflammatory cytokines. The extent of activation is dependent dialysis patients may be related to these cellular events on the dialyzer material used and is considered an index of and, in particular, to the production of cytokines by pebiocompatibility. Cytokines, such as interleukin-1␤ (IL-1␤), tumor necrosis factor-␣ (TNF-␣), and IL-6, may induce an ripheral blood mononuclear cells (PBMCs) [6,7]. Cytoinflammatory state and are believed to play a significant role in kines are a family of pleiotropic polypeptides with a dialysis-related morbidity. The interleukin hypothesis suggests molecular weight ranging from 10 to 45 kD that, prothat the release of proinflammatory cytokines acts as an underduced by different cells in response to inflammatory stimlying pathophysiologic event in hemodialysis-related acute uli, may modulate a variety of functions not only in manifestations, such as fever and hypotension. Nevertheless, a cytokine overproduction may alter sleep pattern in chronic circulating immune cells, but also in mesenchymal, endohemodialyzed patients, thus explaining the presence of sleep thelial, and epithelial cells [8]. There is an increasing disorders in these patients. A potential role of cytokines in body of evidence that the interaction between blood chronic-related morbidity has also been suggested. High levels and dialytic membranes induces the release of several of some inflammatory cytokines are often associated with anemia caused by hyporesponsiveness to erythropoietin. Cytokine cytokines from circulating mononuclear cells, such as production may also play a relevant role in bone remodeling by interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-␣ regulating osteoblast/osteoclast cell functions and parathyroid (TNF-␣), and monocyte chemotactic factor-1 (MCP-1). hormone (PTH). Finally, cytokine release may have a long-The specific action of any of these monocyte-derived term deleterious effect on mortality of uremic patients by altercytokines may be relevant in the pathogenesis of clinical ing immune response and increasing susceptibility to infections. Bioincompatibility of dialytic membranes may also contribute manifestations often observed in end-stage renal disease to malnutrition in dialysis patients by increasing the monocyte (ESRD) patients undergoing chronic hemodialysis [9,10]. release of catabolic cytokines such as TNF-␣ and IL-6. Bioincompatible dialytic treatment may induce an inappropriate monocyte activation and cytokine production, which, in turn, MECHANISMS INVOLVED IN CYTOKINEmay mediate some of the immune and metabolic dysfunction PRODUCTION DURING HEMODIALYSIS associated with hemodialysis. The use of biocompatible dialytic membranes appears to reduce the...

Sepsis remains a serious cause of morbidity and mortality in critically ill patients, with limited therapeutic options available. Of the several disorders connected with sepsis, acute kidney injury (AKI) is one of the major complications. The pathophysiology of sepsis-induced AKI is characterized by severe inflammation in renal parenchyma with endothelial dysfunction, intra-glomerular thrombosis and tubular injury. Endothelial dysfunction is regulated by several mechanisms implicated in cellular de-differentiation, such as endothelial-to-mesenchymal transition (EndMT). Gram-negative bacteria and their cell wall component lipopolysaccharides (LPSs) are frequently involved in the pathogenesis of AKI. The host recognition of LPS requires a specific receptor, which belongs to the Toll-like receptor (TLR) family of proteins, called TLR4, and two carrier proteins, namely the LPS-binding protein (LBP) and cluster of differentiation 14 (CD14). In particular, LBP is released as a consequence of Gram-negative infection and maximizes the activation of TLR4 signalling. Recent findings regarding the emerging role of LBP in mediating sepsis-induced AKI, and the possible beneficial effects resulting from the removal of this endogenous adaptor protein, will be discussed in this review.

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