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Association between serum alkaline phosphatase and primary resistance to erythropoiesis stimulating agents in chronic kidney disease: a secondary analysis of the HERO trial

Badve, Sunil V., Zhang, Lei, Coombes, Jeff S., Pascoe, Elaine M., Cass, Alan, Clarke, Philip, Ferrari, Paolo, McDonald, Stephen P., Morrish, Alicia T., Pedagogos, Eugenie, Perkovic, Vlado, Reidlinger, Donna, Scaria, Anish, Walker, Rowan, Vergara, Liza A., Hawley, Carmel M., Johnson, David W. and HERO Study Collaborative Group (2015). Association between serum alkaline phosphatase and primary resistance to erythropoiesis stimulating agents in chronic kidney disease: a secondary analysis of the HERO trial. Canadian Journal of Kidney Health and Disease,2(33).

Document type: Journal Article
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Title Association between serum alkaline phosphatase and primary resistance to erythropoiesis stimulating agents in chronic kidney disease: a secondary analysis of the HERO trial
Author Badve, Sunil V.
Zhang, Lei
Coombes, Jeff S.
Pascoe, Elaine M.
Cass, Alan
Clarke, Philip
Ferrari, Paolo
McDonald, Stephen P.
Morrish, Alicia T.
Pedagogos, Eugenie
Perkovic, Vlado
Reidlinger, Donna
Scaria, Anish
Walker, Rowan
Vergara, Liza A.
Hawley, Carmel M.
Johnson, David W.
HERO Study Collaborative Group
Journal Name Canadian Journal of Kidney Health and Disease
Publication Date 2015
Volume Number 2
Issue Number 33
ISSN 2054-3581   (check CDU catalogue open catalogue search in new window)
Total Pages 10
Place of Publication United Kingdom
Publisher Sage Publications Ltd.
HERDC Category C1 - Journal Article (DIISR)
Abstract Background
Erythropoiesis stimulating agent (ESA)-resistant anemia is common in chronic kidney disease (CKD).

Objectives

To evaluate the determinants of severity of ESA resistance in patients with CKD and primary ESA-resistance.

Design
Secondary analysis of a randomized controlled trial (the Handling Erythropoietin Resistance with Oxpentifylline, HERO)

Setting and patients
53 adult patients with CKD stage 4 or 5 and primary ESA-resistant anemia (hemoglobin ≤120 g/L, ESA resistance index [ERI] ≥1.0 IU/kg/week/gHb for erythropoietin or ≥0.005 μg/kg/week/gHb for darbepoeitin, no cause for ESA-resistance identified).

Measurements
Iron studies, parathyroid hormone, albumin, liver enzymes, phosphate or markers of oxidative stress and inflammation.

Methods
Participants were divided into tertiles of ERI. Multinomial logistic regression was used to analyse the determinants of ERI tertiles.

Results

All patients, except one, were receiving dialysis for end-stage kidney disease. The mean ± SD ERI values in the low (n = 18), medium (n = 18) and high (n = 17) ERI tertiles were 1.4 ± 0.3, 2.3 ± 0.2 and 3.5 ± 0.8 IU/kg/week/gHb, respectively (P < 0.001). There were no significant differences observed in age, gender, ethnicity, cause of kidney disease, diabetes, iron studies, parathyroid hormone, albumin, liver enzymes, phosphate or markers of oxidative stress and inflammation between the ERI tertiles. The median [inter-quartile range] serum alkaline phosphatase concentrations in the low, medium and high ERI tertiles were 89 [64,121], 99 [76,134 and 148 [87,175] U/L, respectively (P = 0.054). There was a weak but statistically significant association between ERI and serum alkaline phosphatase (R2 = 0.06, P = 0.03). Using multinomial logistic regression, the risk of being in the high ERI tertile relative to the low ERI tertile increased with increasing serum alkaline phosphatase levels (P = 0.02). No other variables were significantly associated with ERI.

Limitations
Small sample size; bone-specific alkaline phosphatase, other markers of bone turnover and bone biopsies not evaluated.

Conclusions
Serum alkaline phosphatase was associated with severity of ESA resistance in ESA-resistant patients with CKD. Large prospective studies are required to confirm this association. (Trial registration: Australian New Zealand Clinical Trials Registry 12608000199314)
Keywords Erythropoiesis stimulating agents
Anemia
Chronic kidney disease
Alkaline phosphatase
Biological marker
Risk factors
Randomized controlled trial
DOI http://dx.doi.org/10.1186/s40697-015-0066-5   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Additional Notes This is an Open Access article distributed under the terms of the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Description for Link Link to CC Attribution 4.0 License
URL https://creativecommons.org/licenses/by/4.0/au


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