• Sunil V Badve, Lei Zhang, Jeff S Coombes, Elaine M Pascoe, Alan Cass, Philip Clarke, Paolo Ferrari, Stephen P McDonald, Alicia T Morrish, Eugenie Pedagogos, Vlado Perkovic, Donna Reidlinger, Anish Scaria, Rowan Walker, Liza A Vergara, Carmel M Hawley, David W Johnson, and HERO Study Collaborative Group.
• Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia ; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia ; Department of Nephrology, Level 2, ARTS Building, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Queensland 4102 Australia.
• Can J Kidney Health Dis. 2015 Jan 1;2:33.

BackgroundErythropoiesis stimulating agent (ESA)-resistant anemia is common in chronic kidney disease (CKD).ObjectivesTo evaluate the determinants of severity of ESA resistance in patients with CKD and primary ESA-resistance.DesignSecondary analysis of a randomized controlled trial (the Handling Erythropoietin Resistance with Oxpentifylline, HERO).Setting And Patients53 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).MeasurementsIron studies, parathyroid hormone, albumin, liver enzymes, phosphate or markers of oxidative stress and inflammation.MethodsParticipants were divided into tertiles of ERI. Multinomial logistic regression was used to analyse the determinants of ERI tertiles.ResultsAll 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 (R(2) = 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.LimitationsSmall sample size; bone-specific alkaline phosphatase, other markers of bone turnover and bone biopsies not evaluated.ConclusionsSerum 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 RegistrationAustralian New Zealand Clinical Trials Registry 12608000199314).

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