title: Pretransplantation erythropoiesis-stimulating agent hyporesponsiveness is associated with increased kidney allograft failure and mortality.
abstract: BACKGROUND
  Poor response to erythropoiesis-stimulating agents (ESA) is associated with morbidity and mortality among dialysis patients. It is unclear whether the risk associated with poor ESA response during dialysis extends beyond kidney transplantation. We examined pretransplantation ESA response and its effect on allograft failure and mortality.
  
  
  METHODS
  The cohort included all adult Medicare recipients from the U.S. Renal Data System who had received a kidney transplant during years 2000 to 2007 and had at least 6 months of hemodialysis immediately before transplantation. ESA hyporesponsiveness was primarily defined as a monthly ESA dose of 75,000 units or higher and hematocrit 33% or less for at least 3 consecutive months in the pretransplantation period. Crude and adjusted Cox proportional hazards models and Kaplan-Meier methods were used to estimate the effect of ESA hyporesponsiveness on allograft failure and all-cause mortality.
  
  
  RESULTS
  The study group consisted of 36,450 patients; 1004 exhibited hyporesponsiveness. The adjusted hazard ratios (95% confidence interval) for allograft failure and mortality after transplantation were 1.23 (1.10-1.42) and 1.61 (1.43-1.81), respectively, supporting that poor ESA response during hemodialysis is associated with adverse posttransplantation outcomes.
  
  
  CONCLUSIONS
  ESA hyporesponsiveness may be useful in identifying potential allograft recipients who are at high risk for subsequent morbidity and mortality and may benefit from more intensive pretransplantation and posttransplantation monitoring.
authors: 1 Department of Medicine, Division of Nephrology and Hypertension, University of North Carolina, Chapel Hill, NC. 2 Cecil G. Sheps Center for Health Services Research, University of North Carolina, Chapel Hill, NC. 3 Pharmacoepidemiology Program Area, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC. 4 Address correspondence to: Nadiesda Costa, M.D., M.P.H., Division of Nephrology and Hypertension, Department of Medicine, University of Maryland School of Medicine, 20 South Greene Street, Room N3W143, Baltimore, MD 21201.
authors: Nadiesda A
authors: NA
authors: Costa
authors: Abhijit V
authors: AV
authors: Kshirsagar
authors: Lily
authors: L
authors: Wang
authors: Randal K
authors: RK
authors: Detwiler
authors: M Alan
authors: MA
authors: Brookhart
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006397:Hematinics / Q000009:adverse effects*; D006400:Hematocrit; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000097:blood / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality*; D008297:Male; D006278:Medicare; D008875:Middle Aged; D011183:Postoperative Complications / Q000401:mortality*; D011300:Preoperative Care; D016016:Proportional Hazards Models; D006435:Renal Dialysis; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D006397:Hematinics
references: N Engl J Med. 2010 Sep 16;363(12):1146-55
references: 20843249
references: J Am Soc Nephrol. 2001 Jul;12(7):1549-1557
references: 11423586
references: JAMA. 2004 Jan 28;291(4):451-9
references: 14747502
references: BMJ. 2009 Oct 23;339:b4018
references: 19854839
references: Clin J Am Soc Nephrol. 2007 Sep;2(5):872-5
references: 17702716
references: Thromb Res. 1995 Jan 15;77(2):133-43
references: 7740505
references: Semin Dial. 2006 Jul-Aug;19(4):285-90
references: 16893405
references: Transplantation. 2010 May 27;89(10):1247-54
references: 20559032
references: Nephrol Dial Transplant. 2000 Nov;15(11):1827-34
references: 11071973
references: J Am Soc Nephrol. 1998 Jul;9(7):1314-7
references: 9644644
references: J Am Soc Nephrol. 2005 Nov;16(11):3437-44
references: 16176999
references: Clin J Am Soc Nephrol. 2009 Jul;4(7):1246-54
references: 19541816
references: Blood. 2000 May 1;95(9):2983-9
references: 10779449
references: Am J Transplant. 2005 Apr;5(4 Pt 2):843-9
references: 15760412
references: Kidney Int. 1999 Feb;55(2):692-9
references: 9987094
references: Nephrol Dial Transplant. 2005 Sep;20 Suppl 8:viii8-12
references: 16079328
references: Semin Dial. 2004 Jan-Feb;17(1):57-60
references: 14717813
references: Am J Kidney Dis. 2006 Oct;48(4 Suppl 2):S1-106
references: 17045862
references: J Am Soc Nephrol. 2011 May;22(5):975-83
references: 21493773
references: Kidney Int. 2008 Sep;74(6):791-8
references: 18596733
references: Am J Kidney Dis. 1999 Jan;33(1):63-72
references: 9915269
references: JAMA. 2010 Mar 3;303(9):857-64
references: 20197532
references: N Engl J Med. 2006 Nov 16;355(20):2085-98
references: 17108343
references: Kidney Int. 2004 Feb;65(2):597-605
references: 14717930
references: Int J Artif Organs. 2004 Aug;27(8):723-7
references: 15478544
references: Am J Kidney Dis. 2000 Mar;35(3):469-76
references: 10692273
references: Transplant Proc. 2008 Nov;40(9):2919-21
references: 19010147
references: Transpl Int. 2010 Mar 1;23(3):277-84
references: 19821956
references: Am J Kidney Dis. 2009 Jul;54(1):59-69
references: 19501439
references: FEMS Immunol Med Microbiol. 2005 Mar 1;43(3):325-30
references: 15708305
references: N Engl J Med. 2004 Apr 1;350(14):1387-97
references: 15070788
references: Am J Kidney Dis. 2002 Nov;40(5):983-9
references: 12407643
references: Clin J Am Soc Nephrol. 2009 Feb;4(2):470-80
references: 19218474
references: Drugs. 2008;68 Suppl 1:3-10
references: 18442296
references: Thromb Haemost. 2002 Oct;88(4):678-85
references: 12362243
references: Circ Cardiovasc Qual Outcomes. 2008 Nov;1(2):92-7
references: 20031795
references: Blood Purif. 2004;22 Suppl 2:26-9
references: 15655319
references: Am J Kidney Dis. 2008 May;51(5):865; author reply 865-6
references: 18436099
references: Clin J Am Soc Nephrol. 2007 Mar;2(2):239-44
references: 17699419
references: Transpl Int. 1992;5 Suppl 1:S116-20
references: 14621752
references: Kidney Int. 1999 Feb;55(2):648-58
references: 9987089
references: Transplantation. 2004 Dec 15;78(11):1670-5
references: 15591958
references: Am J Transplant. 2005 Apr;5(4 Pt 1):757-65
references: 15760399
references: Lancet. 2010 Jan 9;375(9709):132-40
references: 20031199
references: Biochem J. 1984 Apr 1;219(1):1-14
references: 6326753
references: Nephrol Dial Transplant. 2001 Sep;16(9):1863-9
references: 11522871
references: Am J Transplant. 2004 Mar;4(3):438-43
references: 14961999
references: N Engl J Med. 1998 Aug 27;339(9):584-90
references: 9718377
references: Am J Kidney Dis. 2006 May;47(5):815-22
references: 16632020
references: Clin J Am Soc Nephrol. 2008 Jul;3(4):1077-83
references: 18417744
references: Kidney Int. 2002 Nov;62(5):1524-38
references: 12371953
references: Ann Intern Med. 2009 Oct 6;151(7):483-95
references: 19805771
references: Kidney Int. 2005 Jun;67(6):2407-14
references: 15882286
references: Kidney Int. 2004 Dec;66(6):2429-36
references: 15569336
references: Am J Kidney Dis. 2008 Oct;52(4):727-36
references: 18760517
references: Am J Kidney Dis. 1997 Apr;29(4):565-8
references: 9100046
references: Free Radic Biol Med. 1996;20(5):707-27
references: 8721615
references: J Am Soc Nephrol. 2004 Jan;15 Suppl 1:S25-9
references: 14684667
references: Nephrol Dial Transplant. 2005 Feb;20(2):266-70
references: 15647310
references: N Engl J Med. 2006 Nov 16;355(20):2071-84
references: 17108342
references: NDT Plus. 2009 Jan;2(Suppl_1):i18-i26
references: 19461856
references: Annu Rev Nutr. 1985;5:365-90
references: 2992549