Oxidatively-modified and glycated proteins as candidate pro-inflammatory toxins in uremia and dialysis patients.
End stage renal disease (ESRD) patients accumulate blood hallmarks of protein glycation and oxidation. It is now well established that these protein damage products may represent a heterogeneous class of uremic toxins with pro-inflammatory and pro-oxidant properties. These toxins could be directly involved in the pathogenesis of the inflammatory syndrome and vascular complications, which are mainly sustained by the uremic state and bioincompatibility of dialysis therapy. A key underlying event in the toxicity of these proteinaceous solutes has been identified in scavenger receptor-dependent recognition and elimination by inflammatory and endothelial cells, which once activated generate further and even more pronounced protein injuries by a self-feeding mechanism based on inflammation and oxidative stress-derived events. This review examines the literature and provides original information on the techniques for investigating proteinaceous pro-inflammatory toxins. We have also evaluated therapeutic - either pharmacological or dialytic - strategies proposed to alleviate the accumulation of these toxins and to constrain the inflammatory and oxidative burden of ESRD.
Piroddi
M
M
Department of Internal Medicine, Section of Applied Biochemistry and Nutritional Sciences, University of Perugia, Perugia, Italy.
Depunzio
I
I
Calabrese
V
V
Mancuso
C
C
Aisa
C M
CM
Binaglia
L
L
Minelli
A
A
Butterfield
A D
AD
Galli
F
F
D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D008213:Lymphocyte Activation; D015416:Maillard Reaction; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D040901:Proteomics; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D006435:Renal Dialysis; D014511:Uremia / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy
D017127:Glycation End Products, Advanced; D018836:Inflammation Mediators; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species