Despite marked improvements in renal replacement therapy during the last 30 years, the age-adjusted mortality rate in end-stage renal disease (ESRD) patients is still unacceptably high and comparable to that of many malignancies. Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in ESRD patients. However, traditional risk factors can only partially explain the high premature cardiovascular burden in this population. Nontraditional risk factors, including persistent low-grade inflammation, are critical in the pathogenesis of atherosclerosis, vascular calcification, and other causes of CVD and may also contribute to protein-energy wasting and other complications in chronic kidney disease (CKD) patients. Inflammatory biomarkers, such as high sensitivity C-reactive protein and interleukin-6, independently predict mortality in these patients. The causes of inflammation in CKD are multifactorial and include imbalance between increased production (due to multiple sources of inflammatory stimuli such as oxidative stress, acidosis, volume overload, co-morbidities, especially infections, genetic and epigenetic influences, and the dialysis procedure) and inadequate removal (due to decreased glomerular filtration rate or in ESRD patients, inadequate dialytic clearance) of pro-inflammatory cytokines. Though there are currently no established guidelines for the treatment of low-grade inflammation in ESRD patients, several strategies have been proposed, such as lifestyle modifications, pharmacological treatment, and optimization of dialysis. Further studies on pathways involved in pathogenic processes of inflammation in ESRD, and long-term effects of anti-inflammatory interventions targeting production or removal of cytokines or both on premature CVD and clinical outcomes in this patient group are warranted.

The incidence and diagnosis of chronic kidney disease (CKD) is on the rise all over the world. CKD is related to ageing of the society and high morbidity due to lifestyle diseases like diabetes, atherosclerosis, and hypertension. CKD is associated with increased oxidative stress generated by uremic toxicity, chronic inflammatory state, lack of vitamins and microelements, parenteral iron administration, and dialysis procedure itself. In terms of cellular physiology, erythrocytes and blood platelets in particular have effective enzymatic and non-enzymatic antioxidative system. The most efficient enzymatic antioxidants include superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase. Glutathione is the leading non-enzymatic free radical scavenger. In CKD, antioxidative defense is impaired and the abnormal activity of the enzymes and glutathione concentration is described in literature. The imbalance between the formation of reactive oxygen species and antioxidative system efficiency takes part in the pathogenesis of cardiovascular complications. It contributes to increased morbidity and mortality in patients with CKD. The severity of these processes depends on the type of renal replacement therapy; haemodialysis (HD) is more predisposing to such disorders than peritoneal dialysis (PD), or even conservative treatment. This can influence the outcome and the possibility of kidney transplantation. Moreover, the early function of kidney allograft seems to be dependent on perioperative antioxidative ability of platelets, which can play a potential protective role in kidney transplantation.

The type of treatment, age and duration of renal replacement therapy determined significant changes in platelet antioxidative enzymes activities and concentration of GSH, which may enhance the thrombotic complications. PD is associated with lower platelet oxidative stress.

The rarity of the coexistence of these two diseases results in a lack of effective therapy. In such cases sulfone derivatives are still effective and provide an alternative to standard immunosuppression methods. Hyperbaric therapy and plasmapheresis can also play an important complementary role.

Background: Patients suffering from chronic kidney disease (CKD) are exposed to increased oxidative stress and disturbances manifesting in the enzymatic and non-enzymatic antioxidative defence system. The object of the research was to assess the differences between conservative treatment, peritoneal dialysis and haemodialysis in moderating cellular antioxidative agents. Methods: The group examined comprised 145 patients. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase were obtained using kinetic methods. The spectrophotometric method established the concentrations of reduced glutathione, albumin, uric acid, glucose, total protein and lipids. Results: The type of treatment determined significant changes in antioxidative enzyme activities and concentrations of non-enzymatic antioxidative compounds. Conclusions: Peritoneal dialysis provides better antioxidant protection than other types of therapy in CKD and should be considered as first-choice treatment despite more metabolic disorders.

The identification of Klotho gene was a major discovery as the gene encodes a protein regulating multiple functions. A defect in Klotho gene expression in mice results in a phenotype of premature aging including shortened life span, growth retardation, hypogonadism, skin and muscle atrophies, vascular calcification, cognition impairment, motor neuron degeneration and others. This phenotype is associated with phosphate balance disorders and underlines the major function of Klotho in mineral metabolism. As another 2 related paralogs were discovered (beta-Klotho, which is involved in bile acid and energy metabolism, and gamma-Klotho, with a yet to be defined function), this led to the revised naming of Klotho as alpha-Klotho. Two forms of alpha-Klotho protein have been reported: a membrane-bound and a soluble one. Membrane Klotho forms a complex with fibroblast growth factor (FGF) receptors and functions as an obligate co-receptor for the FGF-23 phosphatonin in distal tubules. The soluble form of Klotho seems to function as a humoral factor and regulates glycoproteins on the cell surface including ion channels and growth factors. There is data suggesting that soluble Klotho exerts phosphaturic effects independently of FGF-23. Circulating soluble Klotho is produced either by proteolytic cleavage of the extracellular domain of the transmembrane form by two membrane-anchored proteases (ADAM10 and ADAM17) or by alternative mRNA splicing. In animal models Klotho has been shown to exert pleiotropic actions, including cytoprotection, anti-oxidation, anti-apoptosis, protection of vasculature, promotion of angiogenesis and vascularization, inhibition of fibrogenesis and preservation of stem cells. The exact diagnostic and therapeutic role of Klotho in humans is not fully known yet. The article presents the role of Klotho in physiology and different stages of chronic kidney disease (CKD).

No abstract

No abstract