The Influence of Inflammation on Anemia in CKD Patients

Abstract

Anemia is frequently observed in the course of chronic kidney disease (CKD) and it is associated with diminishing the quality of a patient’s life. It also enhances morbidity and mortality and hastens the CKD progression rate. Patients with CKD frequently suffer from a chronic inflammatory state which is related to a vast range of underlying factors. The results of studies have demonstrated that persistent inflammation may contribute to the variability in Hb levels and hyporesponsiveness to erythropoietin stimulating agents (ESA), which are frequently observed in CKD patients. The understanding of the impact of inflammatory cytokines on erythropoietin production and hepcidin synthesis will enable one to unravel the net of interactions of multiple factors involved in the pathogenesis of the anemia of chronic disease. It seems that anti-cytokine and anti-oxidative treatment strategies may be the future of pharmacological interventions aiming at the treatment of inflammation-associated hyporesponsiveness to ESA. The discovery of new therapeutic approaches towards the treatment of anemia in CKD patients has become highly awaited. The treatment of anemia with erythropoietin (EPO) was associated with great benefits for some patients but not all.

Inhibition of transforming growth factor β1 signaling in resident interstitial cells attenuates profibrotic gene expression and preserves erythropoietin production during experimental kidney fibrosis in mice

“…6,34,64 This is of particular interest because EPO production is also impaired in human fibrotic kidneys. 7,8,40 EPO production declines in damaged kidneys despite prevalent tissue hypoxia, which should normally induce EPO expression through HIF activation. 34,[64][65][66] The reasons for insufficient EPO production in fibrotic kidneys are not completely clear, but are thought to be connected to the metaplastic transformation of interstitial EPOproducing PDGFR-β + cells into myofibroblasts.…”

“…6,[36][37][38][39] Renal fibrosis is associated with a reduced capability of the kidneys to produce erythropoietin. [5][6][7][8][9]34,40 Although the reasons for this have not yet been clearly resolved, it is thought that transformation of interstitial PDGFR-β + cells into myofibroblasts goes hand in hand with the loss of their capability to produce EPO. 5,6,34,41 In view of the major role of interstitial PDGFR-β + cells as native EPO producers and as precursors of myofibroblasts, we were interested to define the role of TGFβ1 signaling in this cell population.…”

Plasma Catestatin Levels and Advanced Glycation End Products in Patients on Hemodialysis

“…HD is associated with a low-grade chronic inflammation and oxidative stress which is due to loss of antioxidants and stimulation of leukocytes during dialysis which triggers production of reactive oxygen species (ROS) [ 42 , 43 , 44 ]. Several recent studies suggested that that protective role of CST is mediated by preventing DNA damage caused by ROS, reducing endoplasmic reticulum stress-induced apoptosis and scavenging free radicals [ 45 , 46 , 47 , 48 ], while the study conducted by Aung et al implied that CST also has an immunomodulatory function, as they determined that CST has a role in inflammation by causing mast cells to release leukotrienes, prostaglandins, cytokines and chemokines [ 49 ].…”

Skeletal Muscle Mass Is Associated With Erythropoietin Response in Hemodialysis Patients

“…Our nding that TSAT was the independent predictor for ERI is in line with the widely accepted recognition that iron de ciency causes ESA hyporesponsiveness. In ammation can lead to ESA hyporesponsiveness [24]. Pro-in ammatory cytokines such as interleukin-6 increases the expression of hepcidin, which is the regulator of iron homeostasis [25][26].…”