Testosterone deficiency is a cause of anaemia and reduced responsiveness to erythropoiesis-stimulating agents in men with chronic kidney disease

Nephrology Dialysis Transplantation

Volumn 27, Issue 2, 2012, Pages 709-715

  Carrero, Juan Jesús ^a   Bárány, Peter ^a   Yilmaz, Mahmut Ilker ^b   Qureshi, Abdul Rashid ^a   Sonmez, Alper ^b   Heimbürger, Olof ^a   Ozgurtas, Tanez ^b   Yenicesu, Mujdat ^b   Lindholm, Bengt ^a   Stenvinkel, Peter ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b GULHANE SCHOOL OF MEDICINE   (Turkey)

Author keywords

androgens; chronic kidney disease; erythropoietin; sex hormones

Indexed keywords

ANTIANEMIC AGENT; HEMOGLOBIN; TESTOSTERONE;

ADULT; ANDROGEN DEFICIENCY; ANEMIA; ARTICLE; CHRONIC KIDNEY DISEASE; COHORT ANALYSIS; CONTROLLED STUDY; DISEASE ASSOCIATION; DISEASE COURSE; DISEASE PREDISPOSITION; DOSE RESPONSE; ERYTHROCYTE COUNT; HEMODIALYSIS; HEMOGLOBIN BLOOD LEVEL; HUMAN; IRON DEFICIENCY ANEMIA; MAJOR CLINICAL STUDY; MALE; PREVALENCE; PRIORITY JOURNAL; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; RISK FACTOR; TESTOSTERONE BLOOD LEVEL; TREATMENT RESPONSE;

AGED; ANALYSIS OF VARIANCE; ANEMIA; COHORT STUDIES; CONFIDENCE INTERVALS; GLOMERULAR FILTRATION RATE; HEMATINICS; HEMOGLOBINS; HUMANS; HYPOGONADISM; KIDNEY FAILURE, CHRONIC; KIDNEY FUNCTION TESTS; LINEAR MODELS; MALE; MIDDLE AGED; MULTIVARIATE ANALYSIS; ODDS RATIO; RENAL DIALYSIS; RETROSPECTIVE STUDIES; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; TESTOSTERONE; TREATMENT OUTCOME;

EID: 84856813533     PISSN: 09310509     EISSN: 14602385     Source Type: Journal    
DOI: 10.1093/ndt/gfr288     Document Type: Article

References (48)

1. Kilpatrick RD, Critchlow CW, Fishbane S et al. Greater epoetin alfa responsiveness is associated with improved survival in hemodialysis patients. Clin J Am Soc Nephrol 2008; 4: 1077-1083
2. Solomon SD, Uno H, Lewis EF et al. Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med 2010; 363: 1146-1155
3. Johnson DW, Pollock CA, Macdougall IC. Erythropoiesis-stimulating agent hyporesponsiveness. Nephrology (Carlton) 2007; 12: 321-330
4. Elliott J,Mishler D, Agarwal R. Hyporesponsiveness to erythropoietin: causes and management. Adv Chronic Kidney Dis 2010; 16: 94-100
5. Stenvinkel P, Barany P. Anaemia, rHuEPO resistance, and cardiovascular disease in end-stage renal failure; links to inflammation and oxidative stress. Nephrol Dial Transplant 2002; 17 (Suppl 5): 32-37
6. Carrero JJ, Stenvinkel P. Inflammation in end-stage renal disease-what have we learned in 10 years? Semin Dial 2010; 23: 498-509
7. Barany P, Divinho-Filho JC, Bergström J. High C-reactive protein is a strong predictor of resistance to erythropoietin in hemodialysis patients. Am J Kidney Dis 1997; 29: 565-568
8. Tangdhanakanond K, Raja R. Effect of statins on erythropoietin responsiveness in type 2-diabetic versus non-diabetic hemodialysis patients. Clin Nephrol 2010; 73: 1-6
9. Abe M, Okada K, Soma M et al. Relationship between insulin resistance and erythropoietin responsiveness in hemodialysis patients. Clin Nephrol 2011; 75: 49-58
10. Brookhart MA, Schneeweiss S, Avorn J et al. The effect of altitude on dosing and response to erythropoietin in ESRD. J Am Soc Nephrol 2008; 19: 1389-1395
11. Kumar VA, Kujubu DA, Sim JJ et al. Vitamin D supplementation and recombinant human erythropoietin utilization in vitamin D-deficient hemodialysis patients. J Nephrol 2011; 24: 98-105
12. Fernández-Balsells MM, Murad MH, Lane M et al. Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab 2010; 95: 2560-2576
13. Kim SW, Hwang JH, Cheon JM et al. Direct and indirect effects of androgens on survival of hematopoietic progenitor cells in vitro. J Korean Med Sci 2005; 20: 409-416
14. Bachman E, Feng R, Travison T et al. Testosterone suppresses hepcidin in men: a potential mechanism for testosterone-induced erythrocytosis. J Clin Endocrinol Metab 2010; 95: 4743-4747
15. Richardson JR Jr, Weinstein MB. Erythropoietic response of dialyzed patients to testosterone administration. Ann Intern Med 1970; 73: 403-407
16. Neff MS, Goldberg J, Slifkin RF et al. A comparison of androgens for anemia in patients on hemodialysis. N Engl J Med 1981; 304: 871-875
17. Gaughan WJ, Liss KA, Dunn SR et al. A 6-month study of low-dose recombinant human erythropoietin alone and in combination with androgens for the treatment of anemia in chronic hemodialysis patients. Am J Kidney Dis 1997; 30: 495-500
18. Lee MS, Ahn SH, Song JH. Effects of adjuvant androgen on anemia and nutritional parameters in chronic hemodialysis patients using lowdose recombinant human erythropoietin. Korean J Intern Med 2002; 17: 167-173
19. Ballal SH, Domoto DT, Polack DC et al. Androgens potentiate the effects of erythropoietin in the treatment of anemia of end-stage renal disease. Am J Kidney Dis 1991; 17: 29-33
20. Sheashaa H, Abdel-Razek W, El-Husseini A et al. Use of nandrolone decanoate as an adjuvant for erythropoietin dose reduction in treating anemia in patients on hemodialysis. Nephron Clin Pract 2005; 99: c102-c106
21. Albaaj F, Sivalingham M, Haynes P et al. Prevalence of hypogonadism in male patients with renal failure. Postgrad Med J 2006; 82: 693-696
22. Gungor O, Kircelli F, Carrero JJ et al. Endogenous testosterone and mortality in male hemodialysis patients: is it the result of aging? Clin J Am Soc Nephrol 2010; 5: 2018-2023
23. Carrero JJ, Qureshi AR, Nakashima A et al. Prevalence and clinical implications of testosterone deficiency in men with endstage renal disease. Nephrol Dial Transplant 2011; 26: 184-190
24. Carrero JJ, Qureshi AR, Parini P et al. Low serum testosterone increases mortality risk among male dialysis patients. J Am Soc Nephrol 2009; 20: 613-620
25. Yilmaz MI, Sonmez A, Qureshi AR et al. Endogenous testosterone associates with endothelial dysfunction and predicts cardiovascular events in men with nondialysis chronic kidney disease. Clin J Am Soc Nephrol 2011; In press
26. Karakitsos D, Patrianakos AP, De Groot E et al. Androgen deficiency and endothelial dysfunction in men with end-stage kidney disease receiving maintenance hemodialysis. Am J Nephrol 2006; 26: 536-543
27. DeLong M, Logan JL, Yong KC et al. Renin-angiotensin blockade reduces serum free testosterone in middle-aged men on haemodialysis and correlates with erythropoietin resistance. Nephrol Dial Transplant 2005; 20: 585-590
28. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2004; 42 (Suppl 3): S1-S202
29. Snaedal S, Heimburger O, Qureshi AR et al. Comorbidity and acute clinical events as determinants of C-reactive protein variation in hemodialysis patients: implications for patient survival. Am J Kidney Dis 2009; 53: 1024-1033
30. Bhasin S, Cunningham GR, Hayes FJ et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2006; 91: 1995-2010
31. Zitzmann M, Faber S, Nieschlag E. Association of specific symptoms and metabolic risks with serum testosterone in older men. J Clin Endocrinol Metab 2006; 91: 4335-4343
32. Grossmann M, Panagiotopolou S, Sharpe K et al. Low testosterone and anaemia in men with type 2 diabetes. Clin Endocrinol (Oxf) 2009; 70: 547-553
33. Bhatia V, Chaudhuri A, Tomar R et al. Low testosterone and high C-reactive protein concentrations predict low hematocrit in type 2 diabetes. Diabetes Care 2006; 29: 2289-2294
34. Yeap BB, Beilin J, Shi Z et al. Serum testosterone levels correlate with haemoglobin in middle-aged and older men. Intern Med J 2009; 39: 532-538
35. Ferrucci L, Maggio M, Bandinelli S et al. Low testosterone levels and the risk of anemia in older men and women. Arch Intern Med 2006; 166: 1380-1388
36. Fonesca R, Rajkumar SV, White WL et al. Anemia after orchiectomy. Am J Hematol 1998; 59: 230-233
37. Haurani FI, Green D. Primary defective iron reutilization. Response to testosterone therapy. Am J Med 1967; 42: 151-158
38. Ashby DR, Gale DP, Busbridge M et al. Plasma hepcidin levels are elevated but responsive to erythropoietin therapy in renal disease. Kidney Int 2009; 75: 976-981
39. Schustack A, Meshiaj D, Waiss Z et al. Intramuscular iron replenishment and replacement combined with testosterone enanthate in maintenance hemodialysis anemia: a follow-up of up to 8 years on 16 patients. Clin Nephrol 1985; 23: 303-306
40. Carrero JJ. Gender differences in chronic kidney disease: underpinnings and therapeutic implications. Kidney Blood Press Res 2010; 33: 383-392
41. Canguven O, Aykose G, Albayrak S et al. Efficacy of testosterone gel in the treatment of erectile dysfunction in hypogonadal hemodialysis patients: a pilot study. Int J Impot Res 2010; 22: 140-145
42. Brockenbrough AT, Dittrich MO, Page ST et al. Transdermal androgen therapy to augment EPO in the treatment of anemia of chronic renal disease. Am J Kidney Dis 2006; 47: 251-262
43. Kalinchenko SY, Tishova YA, Mskhalaya GJ et al. Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study. Clin Endocrinol (Oxf) 2010; 73: 602-612
44. Almeida OP, Yeap BB, Hankey GJ et al. Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men. Arch Gen Psychiatry 2008; 65: 283-289
45. Cauley JA, Ewing SK, Taylor BC et al. Sex steroid hormones in older men: longitudinal associations with 4.5-year change in hip bone mineral density-the osteoporotic fractures in men study. J Clin Endocrinol Metab 2010; 95: 4314-4323
46. Malkin CJ, Jones RD, Jones TH et al. Effect of testosterone on ex vivo vascular reactivity in man. Clin Sci (Lond) 2006; 111: 265-274
47. Kenny AM, Kleppinger A, Annis K et al. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. J Am Geriatr Soc 2010; 58: 1134-1143
48. Basaria S, Coviello AD, Travison TG et al. Adverse events associated with testosterone administration. N Engl J Med 2010; 363: 109-122