Relationship between protein-energy wasting in adults with chronic hemodialysis and the response to treatment with erythropoietin

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Abstract

Background

It is known that one of the leading causes of morbidity in chronic kidney disease (CKD) is the anemic syndrome. Although the pathogenic mechanisms of anemia are multiple, erythropoietin deficiency appears as the dominant factor. Patients in hemodialysis (HD) have a high prevalence of protein energy wasting (PEW) that may explains the poor response to Erythropoietin (EPO).

Methods

Retrospective cohort study of patients on HD from January to December 2014. The participants were classified according to a diagnostic of PEW using the “Malnutrition Inflammation Score” (MIS) and bioimpedance analysis (BIA) measurement of body composition at the start of erythropoietin therapy and after 3 months of follow up. We performed descriptive statistics and analyzed the differences between groups with and without PEW considering their responsiveness. In addition, we calculated the relative risk of EPO resistance, considering p value < 0.05 as statistically significant.

Results

Sixty-one patients ended the follow up. Both groups were similar in basal hemoglobin, hematocrit and other hematopoiesis markers (p = NS). Patients without PEW have a decrease risk for poor response to treatment with EPO (RR = 0.562 [95% CI, 0.329–0.961-]) than those with PEW. Finally, hemoglobin concentrations were evaluated at baseline and every four weeks until week 12, finding a statistically significant improvement only in patients without PEW according MIS ( p < 0.05).

Conclusions

PEW is an incremental predictor of poor responsiveness to EPO in HD patients, thus, it is important to consider correcting malnutrition or wasting for a favorable response to treatment with EPO.

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Most cited references 21

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A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients.

K. Kalantar-Zadeh, J Kopple, G Block … (2001)

Malnutrition inflammation complex syndrome (MICS) occurs commonly in maintenance hemodialysis (MHD) patients and may correlate with increased morbidity and mortality. An optimal, comprehensive, quantitative system that assesses MICS could be a useful measure of clinical status and may be a predictor of outcome in MHD patients. We therefore attempted to develop and validate such an instrument, comparing it with conventional measures of nutrition and inflammation, as well as prospective hospitalization and mortality. Using components of the conventional Subjective Global Assessment (SGA), a semiquantitative scale with three severity levels, the Dialysis Malnutrition Score (DMS), a fully quantitative scoring system consisting of 7 SGA components, with total score ranging between 7 (normal) and 35 (severely malnourished), was recently developed. To improve the DMS, we added three new elements to the 7 DMS components: body mass index, serum albumin level, and total iron-binding capacity to represent serum transferrin level. This new comprehensive Malnutrition-Inflammation Score (MIS) has 10 components, each with four levels of severity, from 0 (normal) to 3 (very severe). The sum of all 10 MIS components ranges from 0 to 30, denoting increasing degree of severity. These scores were compared with anthropometric measurements, near-infrared-measured body fat percentage, laboratory measures that included serum C-reactive protein (CRP), and 12-month prospective hospitalization and mortality rates. Eighty-three outpatients (44 men, 39 women; age, 59 +/- 15 years) on MHD therapy for at least 3 months (43 +/- 33 months) were evaluated at the beginning of this study and followed up for 1 year. The SGA, DMS, and MIS were assessed simultaneously on all patients by a trained physician. Case-mix-adjusted correlation coefficients for the MIS were significant for hospitalization days (r = 0.45; P < 0.001) and frequency of hospitalization (r = 0.46; P < 0.001). Compared with the SGA and DMS, most pertinent correlation coefficients were stronger with the MIS. The MIS, but not the SGA or DMS, correlated significantly with creatinine level, hematocrit, and CRP level. During the 12-month follow-up, 9 patients died and 6 patients left the cohort. The Cox proportional hazard-calculated relative risk for death for each 10-unit increase in the MIS was 10.43 (95% confidence interval, 2.28 to 47.64; P = 0.002). The MIS was superior to its components or different subversions for predicting mortality. The MIS appears to be a comprehensive scoring system with significant associations with prospective hospitalization and mortality, as well as measures of nutrition, inflammation, and anemia in MHD patients. The MIS may be superior to the conventional SGA and the DMS, as well as to individual laboratory values, as a predictor of dialysis outcome and an indicator of MICS.

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A new method for monitoring body fluid variation by bioimpedance analysis: the RXc graph.

Antonio Piccoli, Barbara Rossi, Luana Pillon … (1994)

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Erythropoietic response and outcomes in kidney disease and type 2 diabetes.

Robert Toto, Emmanuel A. Burdmann, Sharon D Solomon … (2010)

Non–placebo-controlled trials of erythropoiesis-stimulating agents (ESAs) comparing lower and higher hemoglobin targets in patients with chronic kidney disease indicate that targeting of a lower hemoglobin range may avoid ESA-associated risks. However, target-based strategies are confounded by each patient's individual hematopoietic response. We assessed the relationship among the initial hemoglobin response to darbepoetin alfa after two weight-based doses, the hemoglobin level achieved after 4 weeks, the subsequent darbepoetin alfa dose, and outcomes in 1872 patients with chronic kidney disease and type 2 diabetes mellitus who were not receiving dialysis. We defined a poor initial response to darbepoetin alfa (which occurred in 471 patients) as the lowest quartile of percent change in hemoglobin level (<2%) after the first two standardized doses of the drug. Patients who had a poor initial response to darbepoetin alfa had a lower average hemoglobin level at 12 weeks and during follow-up than did patients with a better hemoglobin response (a change in hemoglobin level ranging from 2 to 15% or more) (P<0.001 for both comparisons), despite receiving higher doses of darbepoetin alfa (median dose, 232 μg vs. 167 μg; P<0.001). Patients with a poor response, as compared with those with a better response, had higher rates of the composite cardiovascular end point (adjusted hazard ratio, 1.31; 95% confidence interval [CI], 1.09 to 1.59) or death (adjusted hazard ratio, 1.41; 95% CI, 1.12 to 1.78). A poor initial hematopoietic response to darbepoetin alfa was associated with an increased subsequent risk of death or cardiovascular events as doses were escalated to meet target hemoglobin levels. Although the mechanism of this differential effect is not known, these findings raise concern about current target-based strategies for treating anemia in patients with chronic kidney disease. (Funded by Amgen; ClinicalTrials.gov number, NCT00093015.)

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Author and article information

Contributors

Ailema González-Ortiz: ailejgo@gmail.com

Ricardo Correa-Rotter: correa-rotter@gmail.com

Armando Vázquez-Rangel: drarmandovazquez@hotmail.com

Olynka Vega-Vega: olynkavega@gmail.com

Ángeles Espinosa-Cuevas: +52-56550382 , angespinosac@gmail.com , angeles.espinosac@incmnsz.mx

Journal

Journal ID (nlm-ta): BMC Nephrol

Journal ID (iso-abbrev): BMC Nephrol

Title: BMC Nephrology

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2369

Publication date (Electronic): 14 August 2019

Publication date PMC-release: 14 August 2019

Publication date Collection: 2019

Volume: 20

Electronic Location Identifier: 316

Affiliations

[1 ]ISNI 0000 0001 0698 4037, GRID grid.416850.e, Nephrology and Mineral Metabolism Department, , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, ; Vasco de Quiroga No. 15, Col. Belisario Dominguez Sección XVI, Deleg. Tlalpan, 14080 Mexico City, CP Mexico

[2 ]ISNI 0000 0001 2159 0001, GRID grid.9486.3, School of Medicine, Universidad Nacional Autónoma de México, ; Ave. Universidad No. 3000, Col. Ciudad Universitaria, Deleg, Coyoacán, 04510 México City, CP Mexico

[3 ]ISNI 0000 0001 2292 8289, GRID grid.419172.8, Nephrology Department, , Instituto Nacional de Cardiología Ignacio Chávez, ; Juan Badiano No. 1, Colonia Belisario Dominguez Sección XVI, Deleg. Tlalpan, 14080 Mexico City, CP Mexico

[4 ]ISNI 0000 0001 2157 0393, GRID grid.7220.7, Health Care Department, , Universidad Autónoma Metropolitana-Xochimilco, ; Calz. Del Hueso No. 1100, Col. Villa Quietud, Deleg. Coyoacán, 04960 Mexico City, CP Mexico

Article

Publisher ID: 1457

DOI: 10.1186/s12882-019-1457-0

PMC ID: 6694582

PubMed ID: 31412807

SO-VID: 65dbf16b-aeb4-4bd4-81ce-1de756c07883

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 18 December 2017

Date accepted : 8 July 2019

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ScienceOpen disciplines: Nephrology

Keywords: protein energy wasting,hemodialysis,erythropoietin response

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ScienceOpen disciplines: Nephrology

Keywords: protein energy wasting, hemodialysis, erythropoietin response

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Relationship between protein-energy wasting in adults with chronic hemodialysis and the response to treatment with erythropoietin

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Karger: Nephrology

Most cited references 21

A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients.

A new method for monitoring body fluid variation by bioimpedance analysis: the RXc graph.

Erythropoietic response and outcomes in kidney disease and type 2 diabetes.

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Cited by 7

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