Erythropoietin Resistance in Anemia of Chronic Kidney Disease

NCT00526747 | Completed DMC

• 1 other identifier: Pro00008469
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

Our goal of this pilot project is to identify inflammatory biomarkers that correlate with epo-resistance among CKD patients.

Conditions

Anemia; Kidney Failure; Erythropoietin

Study Arms (2)

Epo-resistant

Patients with CKD (estimated GFR \< 60cc/min) not on hemodialysis who are receiving greater than or equal to 100IU/kg/week of epoetin alpha and/or 1mcg/kg/week darbepoetin to obtain target hemoglobin or hematocrit.

Epo-responsive

Patients with CKD (estimated GFR \< 60cc/min) not on hemodialysis who are requiring \<100IU/kg/week of epoetin alpha and/or 1mcg/kg/week of darbepoetin to obtain target hemoglobin/hematocrit.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

CKD anemia clinic patients

You may qualify if:

• prevalent patients greater than or equal to 18 years old with CKD defined as a glomerular filtration rate \< 60 cc/min

You may not qualify if:

• active GI bleeding or history of GI bleed in the prior 3 months
• uncontrolled hyperparathyroidism (PTH\>500)
• untreated iron deficiency (transferrin saturation \< 20% and ferritin \< 100
• overt infection
• active hemolysis
• hemoglobinopathies
• known adverse response to erythropoietin
• prior kidney transplant
• aluminum toxicity

Sponsors & Collaborators

• Duke University: lead

Study Sites (2)

Durham Nephrology Anemia Clinic

Durham, North Carolina, 27704, United States

Location

Duke University Medical Center Anemia Clinic

Durham, North Carolina, 27705, United States

Location

Related Publications (21)

• Rossert J, Gassmann-Mayer C, Frei D, McClellan W. Prevalence and predictors of epoetin hyporesponsiveness in chronic kidney disease patients. Nephrol Dial Transplant. 2007 Mar;22(3):794-800. doi: 10.1093/ndt/gfl716. Epub 2007 Jan 8.

  PMID: 17210593 BACKGROUND

• McClellan WM, Flanders WD, Langston RD, Jurkovitz C, Presley R. Anemia and renal insufficiency are independent risk factors for death among patients with congestive heart failure admitted to community hospitals: a population-based study. J Am Soc Nephrol. 2002 Jul;13(7):1928-36. doi: 10.1097/01.asn.0000018409.45834.fa.

  PMID: 12089390 BACKGROUND

• U.S. Renal Data System, USRDS 2005 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Disease, Bethesda, MD, 2005.

  BACKGROUND

• McMahon LP, Mason K, Skinner SL, Burge CM, Grigg LE, Becker GJ. Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end-stage renal failure. Nephrol Dial Transplant. 2000 Sep;15(9):1425-30. doi: 10.1093/ndt/15.9.1425.

  PMID: 10978402 BACKGROUND

• Evans RW, Rader B, Manninen DL. The quality of life of hemodialysis recipients treated with recombinant human erythropoietin. Cooperative Multicenter EPO Clinical Trial Group. JAMA. 1990 Feb 9;263(6):825-30.

  PMID: 2404150 BACKGROUND

• Wolcott DL, Marsh JT, La Rue A, Carr C, Nissenson AR. Recombinant human erythropoietin treatment may improve quality of life and cognitive function in chronic hemodialysis patients. Am J Kidney Dis. 1989 Dec;14(6):478-85. doi: 10.1016/s0272-6386(89)80148-9.

  PMID: 2596475 BACKGROUND

• Strippoli GF, Craig JC, Manno C, Schena FP. Hemoglobin targets for the anemia of chronic kidney disease: a meta-analysis of randomized, controlled trials. J Am Soc Nephrol. 2004 Dec;15(12):3154-65. doi: 10.1097/01.ASN.0000145436.09176.A7.

  PMID: 15579519 BACKGROUND

• Obrador GT, Roberts T, St Peter WL, Frazier E, Pereira BJ, Collins AJ. Trends in anemia at initiation of dialysis in the United States. Kidney Int. 2001 Nov;60(5):1875-84. doi: 10.1046/j.1523-1755.2001.00002.x.

  PMID: 11703606 BACKGROUND

• Zhang Y, Thamer M, Stefanik K, Kaufman J, Cotter DJ. Epoetin requirements predict mortality in hemodialysis patients. Am J Kidney Dis. 2004 Nov;44(5):866-76.

  PMID: 15492953 BACKGROUND

• Humphries JE. Anemia of renal failure. Use of erythropoietin. Med Clin North Am. 1992 May;76(3):711-25. doi: 10.1016/s0025-7125(16)30349-2.

  PMID: 1578966 BACKGROUND

• Stenvinkel P. Anaemia and inflammation: what are the implications for the nephrologist? Nephrol Dial Transplant. 2003 Nov;18 Suppl 8:viii17-22. doi: 10.1093/ndt/gfg1086.

  PMID: 14607995 BACKGROUND

• Kimmel PL, Phillips TM, Simmens SJ, Peterson RA, Weihs KL, Alleyne S, Cruz I, Yanovski JA, Veis JH. Immunologic function and survival in hemodialysis patients. Kidney Int. 1998 Jul;54(1):236-44. doi: 10.1046/j.1523-1755.1998.00981.x.

  PMID: 9648084 BACKGROUND

• Macdougall IC, Cooper AC. Erythropoietin resistance: the role of inflammation and pro-inflammatory cytokines. Nephrol Dial Transplant. 2002;17 Suppl 11:39-43. doi: 10.1093/ndt/17.suppl_11.39.

  PMID: 12386257 BACKGROUND

• Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004 May;113(9):1271-6. doi: 10.1172/JCI20945.

  PMID: 15124018 BACKGROUND

• Bologa RM, Levine DM, Parker TS, Cheigh JS, Serur D, Stenzel KH, Rubin AL. Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients. Am J Kidney Dis. 1998 Jul;32(1):107-14. doi: 10.1053/ajkd.1998.v32.pm9669431.

  PMID: 9669431 BACKGROUND

• Sitter T, Bergner A, Schiffl H. Dialysate related cytokine induction and response to recombinant human erythropoietin in haemodialysis patients. Nephrol Dial Transplant. 2000 Aug;15(8):1207-11. doi: 10.1093/ndt/15.8.1207.

  PMID: 10910446 BACKGROUND

• Touam M, Guery B, Goupy C, Menoyo V, Drueke T. Hypothyroidism and resistance to human recombinant erythropoietin. Nephrol Dial Transplant. 2004 Apr;19(4):1020-1. doi: 10.1093/ndt/gfg556. No abstract available.

  PMID: 15031379 BACKGROUND

• Danielson B. R-HuEPO hyporesponsiveness--who and why? Nephrol Dial Transplant. 1995;10 Suppl 2:69-73. doi: 10.1093/ndt/10.supp2.69.

  PMID: 7644109 BACKGROUND

• Goicoechea M, Martin J, de Sequera P, Quiroga JA, Ortiz A, Carreno V, Caramelo C. Role of cytokines in the response to erythropoietin in hemodialysis patients. Kidney Int. 1998 Oct;54(4):1337-43. doi: 10.1046/j.1523-1755.1998.00084.x.

  PMID: 9767553 BACKGROUND

• Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004 Dec 17;306(5704):2090-3. doi: 10.1126/science.1104742. Epub 2004 Oct 28.

  PMID: 15514116 BACKGROUND

• Inrig JK, Bryskin SK, Patel UD, Arcasoy M, Szczech LA. Association between high-dose erythropoiesis-stimulating agents, inflammatory biomarkers, and soluble erythropoietin receptors. BMC Nephrol. 2011 Dec 12;12:67. doi: 10.1186/1471-2369-12-67.

  PMID: 22152013 DERIVED

MeSH Terms

Conditions

Anemia; Renal Insufficiency

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Jula Inrig, MD, MHS

  Duke University

  PRINCIPAL INVESTIGATOR

• Lynda Szczech, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Suzanne K Bryskin, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2007
• First Posted: September 10, 2007
• Study Start: August 1, 2007
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: April 11, 2013

Record last verified: 2008-11

Locations

US (2)