Mechanisms of Disease: erythropoietin resistance in patients with both heart and kidney failure

Putten, Karien van der; Braam, Branko; Jie, Kim E.; Gaillard, Carlo A.

doi:10.1038/ncpneph0655

Cited by 154 publications

(112 citation statements)

References 100 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…Patients with PIH had not only a higher EPO use but also, lower hemoglobin levels, indicating some degree of EPO resistance. An obvious link may exist between the EPO hyporesponsiveness and the aforementioned inflammatory phenotype of patients with PIH, which may result in limited iron availability, a reduced number of EPO receptors, and impaired EPO receptor signaling (46). Recent evidence suggests that hypoxemia may affect erythrocyte resilience against oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Intradialytic Hypoxemia and Clinical Outcomes in Patients on Hemodialysis

Meyring-Wösten

Zhang

et al. 2016

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Background and objectives Intradialytic hypoxemia has been recognized for decades, but its associations with outcomes have not yet been assessed in a large patient cohort.Design, setting, participants, & measurements Our retrospective cohort study was conducted between January of 2012 and January of 2015. We recorded blood oxygen saturation every minute during hemodialysis in patients with arteriovenous access. A 6-month baseline period with at least 10 treatments with oxygen saturation measurements preceded a 12-month follow-up. Patients were stratified by the presence or absence of prolonged intradialytic hypoxemia defined as oxygen saturation ,90% for at least one third of the treatment time. Demographic, laboratory, and treatment data and hospitalization and mortality rates were compared between the groups. Multivariate Cox regression analysis was used to assess baseline predictors of all-cause mortality during follow-up.Results In total, 100 (10%) of 983 patients had prolonged intradialytic hypoxemia. These patients were older (+3.6 years; 95% confidence interval, 0.8 to 6.3), had longer dialysis vintage (+1.2 years; 95% confidence interval, 0.3 to 2.1), and had higher prevalence of congestive heart failure (+10.8%; 95% confidence interval, 1.6 to 20.7) and chronic obstructive pulmonary disease (+13%; 95% confidence interval, 5 to 21.2). They also resembled an inflammatory phenotype, with lower serum albumin levels (20.1 g/dl; 95% confidence interval, 20.2 to 0) and higher neutrophil-to-lymphocyte ratios (+1; 95% confidence interval, 0.5 to 1.6). They had lower hemoglobin levels (20.2 g/dl; 95% confidence interval, 20.4 to 0) and required more erythropoietin (+1374 U per hemodialysis treatment; 95% confidence interval, 343 to 2405). During follow-up, all-cause hospitalization (1113 hospitalizations; univariate hazard ratio, 1.46; 95% confidence interval, 1.22 to 1.73) and mortality (89 deaths; adjusted hazard ratio, 1.98; 95% confidence interval, 1.14 to 3.43) were higher in patients with prolonged intradialytic hypoxemia.Conclusions Prolonged intradialytic hypoxemia was associated with laboratory indicators of inflammation, higher erythropoietin requirements, and higher all-cause hospitalization and mortality.

show abstract

Section: Discussionmentioning

confidence: 99%

Intradialytic Hypoxemia and Clinical Outcomes in Patients on Hemodialysis

Meyring-Wösten

Zhang

et al. 2016

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…The scenario of EPO levels that are inappropriately low for the degree of anemia (although in absolute values may be even higher than in the healthy population) (25) has been described in a variety of chronic diseases including congestive heart failure and CKD (17,26). Several inflammatory mechanisms may contribute to this phenomenon of EPO resistance, such as inhibition of the growth of erythroid progenitor cells, down-regulation of EPO-receptor expression, mediation of antagonistic binding to the EPO receptor, and inhibition of downstream signaling cascades (26). Our results that elevated EPO levels were in large part related to the level of inflammation are in line with the described mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Endogenous Erythropoietin and the Association with Inflammation and Mortality in Diabetic Chronic Kidney Disease

Wagner

Alam

Zimmermann

et al. 2011

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

SummaryBackground and objectives Anemia and inflammation are prevalent in diabetic patients with chronic kidney disease (CKD). The role of endogenous erythropoietin (EPO) in the pathophysiology of anemia in chronic diseases and its relationship to clinical outcomes remain uncertain. In this cohort study, we aimed to identify factors associated with endogenous EPO levels and investigate their relation to all-cause mortality. Results Patients (median age, 67 years; 52% men; median duration of diabetes, 10 years; median estimated GFR, 49 ml/min per 1.73 m 2 ) were followed for up to 7.0 years. Forty-one patients died. Elevated EPO levels were independently associated with elevated C-reactive protein, low ferritin, and hypertension, in a multivariate model that also included age, cardiovascular disease, kidney function, albumin, cholesterol, and hemoglobin. Higher EPO levels were independently predictive for mortality, as were age, low levels of albumin, and cardiovascular disease. ConclusionsIn diabetic patients with CKD, elevated endogenous EPO levels were predictive for mortality and were related mainly to markers of inflammation, independent of kidney function, and despite low hemoglobin levels. Understanding the phenomenon of EPO resistance and iron dysregulation caused by inflammation is crucial for effective and safe treatment of anemia in patients with CKD.

show abstract

“…In contrast, in anemia of chronic disease and anemia of cancer, data suggest that hepcidin concentrations are increased, causing decreased absorption of iron and increased sequestration of iron in the reticuloendothelial system, which together account for the observed anemia [1,2,14,19,22]. It is also suggested that patients with chronic kidney disease may have increased hepcidin, which could contribute to their observed renal anemia that is treated with erythropoietin and oral iron [4,24].…”

Section: Introductionmentioning

confidence: 81%

Elisa Method For Serum Hepcidin Quantification In Bulgarian Population

Manolov

Atanasova

Vasilev

et al. 2014

Acta Medica Bulgarica

View full text Add to dashboard Cite

Summary.Hepcidin is a 25-aminoacid cysteine-rich iron regulating peptide. Hepcidin quantifi cation in human blood may provide further insights for the pathogenesis of disorders of iron homeostasis and might prove a valuable tool for clinicians for the differential diagnosis of anaemia. This study describes ELISA immunoassay for hepcidin quantifi cation in human serum. We used a sandwich ELISA method from USCN Life Science inc., that consists of ready to use, pre-coated 96-well strip plate with 2 antihepcidin-25 monoclonal antibodies. A recombinant hepcidin in 16 μg/l concentration is used as a standard; it reconstitutes with 1.0 ml standard diluent to prepare a stock solution. We correlated ELISA results of hepcidin-25 measurements in healthy population with hemodialysis patients. The sandwich ELISA was highly specifi c for hepcidin-25, having a low limit of quantifi cation of 0.020 μg/l. Hepcidin-25 concentrations were increased in hemodialysis patients (median 33.05 μg/l, range 22.31 -60.98 μg/l, n = 10) compared with healthy individuals (median 12.41 μg/l, range 6.05-18.53 μg/l, n = 40). The use of 2 monoclonal antibodies in a sandwich ELISA format provides a robust, convenient and not very expensive method for measuring concentrations of the active form of hepcidin. It should help to improve our understanding of the role of hepcidin in regulating iron metabolism.

show abstract

Mechanisms of Disease: erythropoietin resistance in patients with both heart and kidney failure

Cited by 154 publications

References 100 publications

Intradialytic Hypoxemia and Clinical Outcomes in Patients on Hemodialysis

Intradialytic Hypoxemia and Clinical Outcomes in Patients on Hemodialysis

Endogenous Erythropoietin and the Association with Inflammation and Mortality in Diabetic Chronic Kidney Disease

Elisa Method For Serum Hepcidin Quantification In Bulgarian Population

Contact Info

Product

Resources

About