Comparative short-term safety of bolus versus maintenance iron dosing in hemodialysis patients: a replication study

BMC Nephrology

M Alan Brookhart²  Lily Wang³  Abhijit V Kshirsagar¹  Alan R Ellis³  Janet K Freburger³ 

[1] UNC Kidney Center, 7024 Burnett-Womack, CB# 7155, University of North Carolina, Chapel Hill, NC 27599-7155, North Carolina;Department of Epidemiology, 2101 McGavran-Greenberg Hall, CB# 7435, University of North Carolina, Chapel Hill, NC 27599-7435, North Carolina;Cecil G. Sheps Center for Health Services Research, University of North Carolina, 725 Martin Luther King, Jr. Blvd., CB# 7590, Chapel Hill, NC 27599-7590, North Carolina

关键词: Anemia management;    Intravenous iron;    Hemodialysis;   

Others  :  1082608
DOI  :  10.1186/1471-2369-15-154

 received in 2014-01-08, accepted in 2014-09-15,  发布年份 2014

【 摘 要 】

Background

Recent research has reported that patients receiving bolus (frequent large doses to achieve iron repletion) versus maintenance dosing of iron have an increased short-term risk of infection, but a similar risk of cardiovascular events. We sought to determine whether these findings could be replicated using the same methods and a different data source.

Methods

Clinical data from 6,605 patients of a small U.S. dialysis provider merged with Medicare claims data were examined. Iron dosing patterns (bolus, maintenance, no iron) were identified during 1-month exposure periods and cardiovascular and infection-related outcomes were assessed during 3-month follow-up periods. The effects of bolus versus maintenance dosing were assessed using Cox proportional hazards regression analyses to estimate hazard ratios and semiparametric additive risk models to estimate hazard rate differences, controlling for demographic and clinical characteristics, laboratory values and medications, and comorbidities.

Results

48,050 exposure/follow-up periods were examined. 13.9 percent of the exposure periods were bolus dosing, 49.3 percent were maintenance dosing, and the remainder were no iron use. All of the adjusted hazard ratios were >1.00 for the infection-related outcomes, suggesting that bolus dosing increases the risk of these events. The effects were greatest for hospitalized for infection of any major organ system (hazard ratio 1.13 (1.03, 1.24)) and use of intravenous antibiotics (hazard ratio 1.08 (1.02, 1.15). When examining the subgroup of individuals with catheters, the hazard ratios for the infection-related outcomes were generally greater than in the overall sample. There was little association between type of dosing practice and cardiovascular outcomes.

Conclusions

Results of this study provide further evidence of the association between bolus dosing and increased infection risk, particularly in the subgroup of patients with a catheter, and of the lack of an association between dosing practices and cardiovascular outcomes.

【 授权许可】

   
2014 Freburger et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Besarab A, Kaiser JW, Frinak S: A study of parenteral iron regimens in hemodialysis patients. Am J Kidney Dis 1999, 34(1):21-28.
• [2]Charytan C, Levin N, Al-Saloum M, Hafeez T, Gagnon S, Van Wyck DB: Efficacy and safety of iron sucrose for iron deficiency in patients with dialysis-associated anemia: North American clinical trial. Am J Kidney Dis 2001, 37(2):300-307.
• [3]Coyne DW, Kapoian T, Suki W, Singh AK, Moran JE, Dahl NV, Rizkala AR: Ferric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: results of the Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) Study. J Am Soc Nephrol 2007, 18(3):975-984.
• [4]Kshirsagar AV, Freburger JK, Ellis AR, Wang L, Winkelmayer WC, Brookhart MA: The comparative short-term effectiveness of iron dosing and formulations in U.S. hemodialysis patients. Am J Med 2013, 126(6):541. e541-541.e514
• [5]Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, Burger HU, Scherhag A: Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006, 355(20):2071-2084.
• [6]Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, Feyzi JM, Ivanovich P, Kewalramani R, Levey AS, Lewis EF, Mcgill JB, McMurray JJ, Parfrey P, Parving HH, Remuzzi G, Singh AK, Solomon SD, Toto R, TREAT Investigators: A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 2009, 361(21):2019-2032.
• [7]Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D: Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006, 355(20):2085-2098.
• [8]Brewster UC: Intravenous iron therapy in end-stage renal disease. Semin Dial 2006, 19(4):285-290.
• [9]Parkkinen J, von Bonsdorff L, Peltonen S, Gronhagen-Riska C, Rosenlof K: Catalytically active iron and bacterial growth in serum of haemodialysis patients after i.v. iron-saccharate administration. Nephrol Dial Transplant 2000, 15(11):1827-1834.
• [10]Brewster UC, Perazella MA: Intravenous iron and the risk of infection in end-stage renal disease patients. Semin Dial 2004, 17(1):57-60.
• [11]Bullen JJ, Rogers HJ, Spalding PB, Ward CG: Iron and infection: the heart of the matter. FEMS Immunol Med Microbiol 2005, 43(3):325-330.
• [12]Collins AJ, Ebben J, Ma JZ, Xia H: Iron dosing patterns and mortality [abstract]. J Am Soc Nephrol 1998, 9:250A.
• [13]Halliwell B, Gutteridge JM: Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 1984, 219(1):1-14.
• [14]Martin-Malo A, Merino A, Carracedo J, Alvarez-Lara MA, Ojeda R, Soriano S, Crespo R, Ramirez R, Aljama P: Effects of intravenous iron on mononuclear cells during the haemodialysis session. Nephrol Dial Transplant 2012, 27(6):2465-2471.
• [15]Sevanian A, Hochstein P: Mechanisms and consequences of lipid peroxidation in biological systems. Annu Rev Nutr 1985, 5:365-390.
• [16]Berliner JA, Heinecke JW: The role of oxidized lipoproteins in atherogenesis. Free Radic Biol Med 1996, 20(5):707-727.
• [17]Himmelfarb J, Stenvinkel P, Ikizler TA, Hakim RM: The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int 2002, 62(5):1524-1538.
• [18]Brookhart MA, Freburger JK, Ellis K, Wang L, Winkelmayer WC, Kshirsagar AV: Infection risk with bolus versus maintenance iron supplementation in hemodialysis patients. J Am Nephrol Soc 2013, 24(7):1151-1158.
• [19]Kshirsagar AV, Freburger JK, Ellis AR, Wang L, Winkelmayer WC, Brookhart MA: The comparative short-term cardiovascular safety of intravenous iron dosing in hemodialysis patients. PLOS One 2013, 8(11):e78930.
• [20]U.S. Renal Data System Coordinating Center: Researcher's Guide to the USRDS Database,2011. Bethesda, MD: National Institutes of Health, NIDDK; 2012.
• [21]Elixhauser A, Steiner C, Harris DR, Coffey RM: Comorbidity measures for use with administrative data. Med Care 1998, 36(1):8-27.
• [22]Xie X, Strickler HD, Xue X: Additive hazard regression models: an application to the natural history of human papillomavirus. Comput Math Methods Med 2013, 2013:796270.
• [23]Lin DY, Wei LJ: The robust inference for the proportional hazards model. J Am Stat Assoc 1989, 84:1074-1078.
• [24]Robins JM, Hernan MA, Brumback B: Marginal structural models and causal inference in epidemiology. Epidemiology 2000, 11(5):550-560.
• [25]Hernan MA, Brumback B, Robins JM: Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men. Epidemiology 2000, 11(5):561-570.