Renal Anemia of Inflammation: The Name Is Self-Explanatory

Yılmaz, Mahmut İlker; Solak, Yalçın; Covic, Adrian; Goldsmith, David; Kanbay, Mehmet

doi:10.1159/000328037

Cited by 66 publications

(68 citation statements)

References 98 publications

(49 reference statements)

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“…The role of inflammation in the pathogenesis of anemia has been demonstrated for different disease states including chronic kidney disease [20]. Inflammation at the levels observed in ESRD patients suppresses the proliferation of erythroid progenitor cells.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin Resistance Index and the All-Cause Mortality of Chronic Hemodialysis Patients

et al. 2014

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Background: Evidence suggests hemodialysis (HD) patients with resistance to erythropoiesis-stimulating agents (ESA) have a higher mortality rate. We investigated the association between ESA responsiveness and mortality in our HD population. Methods: A prospective cohort study of chronic HD patients was conducted at Jyoban Hospital in Fukushima, Japan. We collected data on patient demographic factors, comorbidities, dialysis vintage, body weight, ESA dose and hemoglobin concentration, as well as data on known risk factors for ESA hyporesponsiveness. The erythropoietin resistance index (ERI) was calculated by dividing the weekly body-weight-adjusted epoetin dose by the hemoglobin concentration. The association between ESA hyporesponsiveness estimated by the highest tertile of ERI and mortality was investigated by using the Cox proportional hazards model with adjustments for demographic factors, comorbidities, dialysis adequacy and serum biochemical data. Results: A total of 248 patients were included as subjects in the cohort, and their overall 2-year mortality rate was 13.3%. According to the results of the Kaplan-Meier analysis, patients with an ERI in the highest tertile had significantly higher mortality than patients with an ERI in the lower two tertiles (p = 0.0121). The highest ERI tertile was associated with higher all-cause mortality in both the unadjusted hazards model (hazard ratio, HR: 4.429; 95% CI: 1.249-15.704) and the adjusted hazards model (HR: 4.204; 95% CI: 1.173-15.065). Conclusions: A higher degree of resistance to ESA in chronic HD patients is associated with increased mortality.

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Section: Discussionmentioning

confidence: 99%

Erythropoietin Resistance Index and the All-Cause Mortality of Chronic Hemodialysis Patients

et al. 2014

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“…This result is perhaps because the mean urea reduction ratio at baseline in our study was high (70%) (31), and by 6 months, it rose even higher (72%), indicating that few, if any, participants were underdialyzed. It is also possible that carbamylation reflects a high inflammatory state, which is known to lead to EPO resistance through multiple mechanisms (1,33,34). Our data included measurements of the inflammatory markers IL-6 and myeloperoxidase as well as albumin and ferritin, which have been shown to correlate with inflammation and EPO resistance (35,36).…”

Section: Discussionmentioning

confidence: 99%

Carbamylation of Serum Albumin and Erythropoietin Resistance in End Stage Kidney Disease

Kalim

Tamez

Wenger

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives The mechanisms underlying erythropoietin resistance are not fully understood. Carbamylation is a post-translational protein modification that can alter the function of proteins, such as erythropoietin. The hypothesis of this study is that carbamylation burden is independently associated with erythropoietin resistance.Design, setting, participants, & measurements In a nonconcurrent prospective cohort study of incident hemodialysis patients in the United States, carbamylated albumin, a surrogate of overall carbamylation burden, in 158 individuals at day 90 of dialysis initiation and erythropoietin resistance index (defined as average weekly erythropoietin dose [U] per kg body weight per hemoglobin [g/dl]) over the subsequent 90 days were measured. Linear regression was used to describe the relationship between carbamylated albumin and erythropoietin resistance index. Logistic regression characterized the relationship between erythropoietin resistance index, 1-year mortality, and carbamylation.Results The median percent carbamylated albumin was 0.77% (interquartile range=0.58%-0.93%). Median erythropoietin resistance index was 18.7 units/kg per gram per deciliter (interquartile range=8.1-35.6 units/kg per gram per deciliter). Multivariable adjusted analysis showed that the highest quartile of carbamylated albumin was associated with a 72% higher erythropoietin resistance index compared with the lowest carbamylation quartile (P=0.01). Increasing erythropoietin resistance index was associated with a higher risk of death (odds ratio per unit increase in log-erythropoietin resistance index, 1.69; 95% confidence interval, 1.06 to 2.70). However, the association between erythropoietin resistance index and mortality was no longer statistically significant when carbamylation was included in the analysis (odds ratio, 1.44; 95% confidence interval, 0.87 to 2.37), with carbamylation showing the dominant association with death (odds ratio for high versus low carbamylation quartile, 4.53; 95% confidence interval, 1.20 to 17.10).Conclusion Carbamylation was associated with higher erythropoietin resistance index in incident dialysis patients and a better predictor of mortality than erythropoietin resistance index.

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“…The role of inflammation in the pathogenesis of anemia has been demonstrated in different disease states, including CKD [19]. Inflammation, at levels observed in ESRD patients suppresses proliferation of erythroid progenitor cells.…”

Section: Discussionmentioning

confidence: 99%

Higher Doses of Erythropoietin-Stimulating Agents and Hyporesponsiveness to Their Effects Are Associated with Increased Mortality among Prevalent Hemodialysis Patients

Nishio

Chhatkuli

Jennie³

et al. 2013

Blood Purif

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Background: Attempts to achieve near-normal hemoglobin levels have been associated with higher mortality among chronic kidney disease patients. Evidence suggests a higher mortality rate for those with resistance to erythropoietin-stimulating agents (ESA). We investigated the association between responsiveness to ESA, dose of ESA and mortality in our hemodialysis population. Methods: A retrospective cohort study of chronic hemodialysis patients receiving dialysis was conducted at the University of Virginia facilities. We collected data on patient demographics, comorbidities, dialysis vintage, vascular access type, body weight, ESA dose and hemoglobin, as well as data on known risk factors for ESA hyporesponsiveness. Vital status was determined 30 months later. The association between ESA responsiveness and mortality was investigated by using the Cox proportional hazard model adjusting for demographics, comorbidities, access type, dialysis adequacy, serum albumin, serum parathyroid hormone and ferritin concentrations. Results: A total of 606 patients were included. The overall 30-month mortality was 35.8%. Compared to those in the lowest tertile of ESA hyporesponsiveness, patients in the middle and upper tertiles had significantly higher mortality (hazard ratio, HR: 1.64, 95% CI: 1.14-2.37, and HR: 2.08, 95% CI: 1.46-2.97, respectively). In the Cox proportional hazard model each unit increment in the ESA resistance index was associated with an HR of 2.27 (95% CI: 1.60-3.23) for mortality. In this model each 1-unit increment in ESA dose/kg or each 100-μg increment in absolute darbepoetin alfa dose were associated with a 9% increased risk of mortality (HR: 1.09, 95% CI: 1.04-1.13, and HR: 1.09, 95% CI: 1.03-1.15, respectively). Conclusions: Among prevalent hemodialysis patients, a higher degree of resistance to and higher doses of ESA are associated with increased mortality.

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Renal Anemia of Inflammation: The Name Is Self-Explanatory

Cited by 66 publications

References 98 publications

Erythropoietin Resistance Index and the All-Cause Mortality of Chronic Hemodialysis Patients

Erythropoietin Resistance Index and the All-Cause Mortality of Chronic Hemodialysis Patients

Carbamylation of Serum Albumin and Erythropoietin Resistance in End Stage Kidney Disease

Higher Doses of Erythropoietin-Stimulating Agents and Hyporesponsiveness to Their Effects Are Associated with Increased Mortality among Prevalent Hemodialysis Patients

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