TY - JOUR AU - Hawley C. AU - Pascoe E. AU - Pedagogos E. AU - McDonald S. AU - Zhang L. AU - Ferrari P. AU - Johnson D. AU - Walker R. AU - Cass A. AU - Reidlinger D. AU - Badve S. AU - Clarke P. AU - Morrish A. AU - Scaria A. AU - Vergara L. AU - Coombes J. AU - Perkovic Vlado AB -

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 /=1.0 IU/kg/week/gHb for erythropoietin or >/=0.005 mug/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 (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. 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).

AD - 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.
Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia ; Department of Nephrology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
School of Human Movement Studies, University of Queensland, Brisbane, Australia.
Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia.
Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia ; Menzies School of Health Research, Darwin, Australia.
Centre for Health Policy, Programs & Economics, University of Melbourne, Melbourne, Australia.
Department of Nephrology, Prince of Wales Hospital, Sydney, Australia.
Department of Nephrology and Transplantation Services, University of Adelaide at Central Northern Adelaide Renal and Transplantation Services, Adelaide, Australia.
Department of Nephrology, Royal Melbourne Hospital, Melbourne, Australia.
Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia ; The George Institute for Global Health, Sydney, Australia.
Department of Renal Medicine, The Alfred Hospital, Melbourne, Australia.
Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia ; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia. AN - 26284153 BT - Canadian journal of kidney health and disease C2 - PMC4538753 DP - NLM ET - 2015/08/19 LA - eng LB - R&M
AUS N1 - 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
England
Can J Kidney Health Dis. 2015 Aug 18;2:33. doi: 10.1186/s40697-015-0066-5. eCollection 2015. N2 -

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 /=1.0 IU/kg/week/gHb for erythropoietin or >/=0.005 mug/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 (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. 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).

PY - 2015 SN - 2054-3581 (Electronic)
2054-3581 (Linking) EP - 33 T2 - Canadian journal of kidney health and disease TI - Association between serum alkaline phosphatase and primary resistance to erythropoiesis stimulating agents in chronic kidney disease: a secondary analysis of the HERO trial VL - 2 Y2 - FY16 ER -