The role of Toll-like receptors in renal diseases

Abstract

Toll-like receptors (TLRs) have a key role in innate immunity. These receptors recognize both pathogen-associated molecular patterns and molecules that are released from damaged tissue. TLRs mediate signal transduction pathways through the activation of transcription factors that regulate the expression of proinflammatory cytokines and chemokines and are required for the development of adaptive immune responses. TLRs might have an important role in the pathogenesis of renal diseases: their exaggerated activation is associated with ischemic kidney damage, acute kidney injury, end-stage renal failure, acute tubulointerstitial nephritis, acute renal transplant rejection and delayed allograft function. As the results of previous studies concerning the role of TLRs in renal diseases are conflicting, further work is needed to determine the exact role of these receptors and to evaluate strategies to prevent TLR-mediated local inflammation. This Review discusses the evidence supporting a role for TLRs in contrasting bacterial infections and in causing or aggravating renal conditions when TLR activation leads to a harmful inflammatory response.

Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

“…Patients with CKD might have increased susceptibility to develop statin intolerance since multiple abnormalities like endothelial dysfunction, enhanced oxidative stress, systemic inflammation, electrolyte imbalances, or proteinuria are simultaneously present [151,152]. Recent Kid ney Disease: Improving Global Outcomes (KDIGO) guidelines regarding the use of cholesterol lowering medications in adults and children with known CKD stated the potential benefits of a new strategy named fire-and-forget for CKD patients, suggesting not to measure LDL-C unless the results would alter management [153].…”

LRRC19 expressed in the kidney induces TRAF2/6-mediated signals to prevent infection by uropathogenic bacteria

“…12). These TLRs are involved in preventing infection by both Gram-negative and Gram-positive pathogenic bacteria by modulating the expression of inflammatory cytokines, chemokines and antimicrobial peptides and proteins 13 . For example, TLR4, which recognizes lipopolysaccharide (LPS), the main component of Gramnegative bacterial cell wall, induces the inflammatory responses to UPEC 14 .…”

The costimulatory immunogen LPS induces the B-Cell clones that infiltrate transplanted human kidneys

“…Thus, although one can debate the pathophysiologic consequences of the appearance of the B-cell clusters themselves in the kidney, the infectious process that initiates their homing and proliferation is very likely to be harmful by a variety of mechanisms including production of proinflammatory cytokines and chemokines when the TLR is activated (46). While much study will be necessary to validate the role, if any, of infection in chronic kidney rejection, such confirmation would be important because coli cell extracts and BSA with the sera from the different cohorts.…”