The Effect of Pentoxifylline on Oxidative Stress in Chronic Kidney Disease Patients with Erythropoiesis-stimulating Agent Hyporesponsiveness: Sub-study of the HERO Trial

Overview

Journal Redox Rep

Specialties Biochemistry
Biology
Endocrinology

Date 2015 Jun 18

PMID 26083328

Citations 4

Authors

Lei Zhang

Jeff Coombes

Elaine M Pascoe

Sunil V Badve

Kim Dalziel

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

The Hero Study Collaborative Group

Affiliations

Soon will be listed here.

Abstract

Objective: Pentoxifylline has previously been shown to increase haemoglobin levels in patients with chronic kidney disease (CKD) and erythropoietin-stimulating agent (ESA)-hyporesponsive anaemia in the HERO multi-centre double-blind, randomized controlled trial. The present study evaluated the effects of pentoxifylline on oxidative stress in ESA-hyporesponsive CKD patients.

Methods: This sub-study of the HERO trial compared 15 patients in the pentoxifylline arm (400 mg daily) and 17 in the matched placebo arm on oxidative stress markers: plasma total F2-isoprostanes, protein carbonyls, glutathione peroxidase (GPX), and superoxide dismutase (SOD) activities.

Results: Pentoxifylline did not significantly alter total F2-isoprostanes (adjusted mean difference (MD) 35.01 pg/ml, P = 0.11), SOD activity (MD 0.82 U/ml, P = 0.07), GPX activity (MD -6.06 U/l, P = 0.09), or protein carbonyls (MD -0.04 nmol/mg, P = 0.52). Replicating results from the main study, pentoxifylline significantly increased haemoglobin concentration compared with controls (MD 7.2 g/l, P = 0.04).

Conclusions: Pentoxifylline did not alter oxidative stress biomarkers, suggesting that alternative mechanisms may be responsible for the agent's ability to augment haemoglobin levels in CKD patients with ESA-hyporesponsive anaemia.

Citing Articles

Antioxidants for adults with chronic kidney disease.

Colombijn J, Hooft L, Jun M, Webster A, Bots M, Verhaar M Cochrane Database Syst Rev. 2023; 11:CD008176.

PMID: 37916745 PMC: 10621004. DOI: 10.1002/14651858.CD008176.pub3.

Oxidative stress: An essential factor in the process of arteriovenous fistula failure.

Hu K, Guo Y, Li Y, Lu C, Cai C, Zhou S Front Cardiovasc Med. 2022; 9:984472.

PMID: 36035909 PMC: 9403606. DOI: 10.3389/fcvm.2022.984472.

Are Antioxidants Useful in Preventing the Progression of Chronic Kidney Disease?.

Casanova A, Lopez-Hernandez F, Vicente-Vicente L, Morales A Antioxidants (Basel). 2021; 10(11).

PMID: 34829540 PMC: 8614781. DOI: 10.3390/antiox10111669.

The molecular mechanisms of hemodialysis vascular access failure.

Brahmbhatt A, Remuzzi A, Franzoni M, Misra S Kidney Int. 2016; 89(2):303-316.

PMID: 26806833 PMC: 4734360. DOI: 10.1016/j.kint.2015.12.019.

References

Handelman G, Walter M, Adhikarla R, Gross J, Dallal G, Levin N . Elevated plasma F2-isoprostanes in patients on long-term hemodialysis. Kidney Int. 2001; 59(5):1960-6. DOI: 10.1046/j.1523-1755.2001.0590051960.x. View

Ramos L, Shintani A, Ikizler T, Himmelfarb J . Oxidative stress and inflammation are associated with adiposity in moderate to severe CKD. J Am Soc Nephrol. 2008; 19(3):593-9. PMC: 2391046. DOI: 10.1681/ASN.2007030355. View

Levine R, Garland D, Oliver C, Amici A, Climent I, Lenz A . Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 1990; 186:464-78. DOI: 10.1016/0076-6879(90)86141-h. View

Suliman H, Ali M, Piantadosi C . Superoxide dismutase-3 promotes full expression of the EPO response to hypoxia. Blood. 2004; 104(1):43-50. DOI: 10.1182/blood-2003-07-2240. View

Johnson D, Hawley C, Rosser B, Beller E, Thompson C, Fassett R . Oxpentifylline versus placebo in the treatment of erythropoietin-resistant anaemia: a randomized controlled trial. BMC Nephrol. 2008; 9:8. PMC: 2519060. DOI: 10.1186/1471-2369-9-8. View

Solomon S, Uno H, Lewis E, Eckardt K, Lin J, Burdmann E . Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med. 2010; 363(12):1146-55. DOI: 10.1056/NEJMoa1005109. View

Himmelfarb J, Phinney S, Ikizler T, Kane J, McMonagle E, Miller G . Gamma-tocopherol and docosahexaenoic acid decrease inflammation in dialysis patients. J Ren Nutr. 2007; 17(5):296-304. DOI: 10.1053/j.jrn.2007.05.011. View

Wheeler C, Salzman J, Elsayed N, Omaye S, Korte Jr D . Automated assays for superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity. Anal Biochem. 1990; 184(2):193-9. DOI: 10.1016/0003-2697(90)90668-y. View

Johnson D, Pascoe E, Badve S, Dalziel K, Cass A, Clarke P . A randomized, placebo-controlled trial of pentoxifylline on erythropoiesis-stimulating agent hyporesponsiveness in anemic patients with CKD: the Handling Erythropoietin Resistance With Oxpentifylline (HERO) trial. Am J Kidney Dis. 2014; 65(1):49-57. DOI: 10.1053/j.ajkd.2014.06.020. View

10.

Hung S, Lin Y, Tarng D . Erythropoiesis-stimulating agents in chronic kidney disease: what have we learned in 25 years?. J Formos Med Assoc. 2013; 113(1):3-10. DOI: 10.1016/j.jfma.2013.09.004. View

11.

Deved V, Poyah P, James M, Tonelli M, Manns B, Walsh M . Ascorbic acid for anemia management in hemodialysis patients: a systematic review and meta-analysis. Am J Kidney Dis. 2009; 54(6):1089-97. DOI: 10.1053/j.ajkd.2009.06.040. View

12.

Roger S, Cooper B . What is the practical conversion dose when changing from epoetin alfa to darbepoetin outside of clinical trials?. Nephrology (Carlton). 2004; 9(4):223-8. DOI: 10.1111/j.1440-1797.2004.00261.x. View

13.

Kamgar M, Zaldivar F, Vaziri N, Pahl M . Antioxidant therapy does not ameliorate oxidative stress and inflammation in patients with end-stage renal disease. J Natl Med Assoc. 2009; 101(4):336-44. DOI: 10.1016/s0027-9684(15)30881-6. View

14.

Stauffer M, Fan T . Prevalence of anemia in chronic kidney disease in the United States. PLoS One. 2014; 9(1):e84943. PMC: 3879360. DOI: 10.1371/journal.pone.0084943. View

15.

Macdougall I, Cooper A . 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. View

16.

Briskey D, Wilson G, Fassett R, Coombes J . Optimized method for quantification of total F(2)-isoprostanes using gas chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2014; 90:161-6. DOI: 10.1016/j.jpba.2013.11.028. View

17.

. KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. Am J Kidney Dis. 2007; 50(3):471-530. DOI: 10.1053/j.ajkd.2007.06.008. View

18.

Biasioli S, Schiavon R, Petrosino L, Cavallini L, De Fanti E, Zambello A . Do different dialytic techniques have different atherosclerotic and antioxidant activities?. ASAIO J. 2001; 47(5):516-21. DOI: 10.1097/00002480-200109000-00024. View

19.

Cooper A, Mikhail A, Lethbridge M, Kemeny D, Macdougall I . Pentoxifylline improves hemoglobin levels in patients with erythropoietin-resistant anemia in renal failure. J Am Soc Nephrol. 2004; 15(7):1877-82. DOI: 10.1097/01.asn.0000131523.17045.56. View

20.

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