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Effect of Growth Hormone on Biomarkers of Nutrition and Cardiovascular Disease
mortality of 40% (n=108) was found in the GH-treated group diabetes, and these subjects will require careful monitoring and
compared with 20% (n=51) in the placebo-treated group (p=0.001).
additional diabetes treatment if this occurs. A number of subjects with
However, previous trials with smaller numbers of subjects but diabetes previously controlled on oral agents may require insulin
comparable doses have demonstrated beneficial or no effects of GH therapy during treatment with GH in order to achieve and maintain
treatment in ICU patients.
appropriate levels of glucose control.
GH has both direct and indirect effects on glucose homeostasis, and A New Phase III Trial Has Been Initiated
treatment with GH may have an impact on glucose metabolism that can Given the correlation between morbidity/mortality and biochemical
be measured clinically. One trial with four weeks of treatment with GH in markers of protein-energy malnutrition, it is appropriate to assess the
dialysis patients resulted in an initial increase in blood glucose, reaching impact of GH on subjects on chronic HD with evidence of malnutrition.
steady state after two weeks.
Another trial of six months duration Clinical studies support the potential beneficial effects of low doses of
found no difference in blood glucose between zero and six months, and Norditropin in this condition.
Increasing the dialysis dose and
a small but non-significant decrease in insulin levels.
This may reflect attempts to increase the nutritional status through dietary interventions
direct beneficial effect on body composition and a subsequent indirect are cumbersome and can at best correct only a minor part of the
effect on glucose metabolism. The studies used a GH dose of 66.7 and malnourished state of the majority of patients on chronic MHD. Thus,
28.6g/kg/day, respectively. In registered indications such as Turner major unmet medical need exists.
syndrome, GH doses of 50–67g/kg/day are used without evidence of an
increased risk of developing diabetes. In addition, the results from the A new global phase III trial will be launched in 2007. It is a
recently performed phase II trial
showed that there were no serious multinational study including 2,500 patients on chronic MHD. The
safety concerns with regard to glucose metabolism in any of the goal for the trial is to establish the efficacy and safety of Norditropin
treatment groups (20, 35 and 50µg/kg/day). on mortality in the chronic HD population during a treatment period
of 24 months. The procedures for diagnosis, treatment and
Clinical experience in acromegaly, a state of GH excess, indicates that withdrawal to be used in the trial are aimed at adapting the current
patients with co-existing diabetes often have worsening of clinical guidelines to meet the realities of daily clinical practice in a
hyperglycaemia that improves when GH levels are reduced. Patients dialysis population. Based upon feedback from regulatory authorities,
with diabetes have differing degrees of insulin resistance and different subjects with diabetes will be included in the present trial as they
levels of endogenous beta-cell function, so the response of an represent a substantial percentage of the chronic HD population. The
individual with diabetes to GH cannot be predicted prior to the start treatment of patients with diabetes will be monitored carefully to
of treatment. It is possible that there will be an accentuation of the assure that appropriate therapeutic interventions are undertaken if
effects of GH on glucose metabolism in subjects with pre-existing glycaemic control worsens. ■
1. United States Renal Data System Annual Report 2006. 21. Leon JB, Majerle AD, Soinski JA, et al., J Ren Nutr, 2001;11(1): 40. Saadeh E, Ikizler TA, Shyr Y, J Renal Nutr, 2001;11(4):212–19.
2. Danish Society of Nephrology: Danish National Registry Report 9–15. 41. Pupim LB, Flakoll PJ, Yu C, Ikizler TA, Am J Clin Nutr,
on Dialysis and Transplantation in Denmark 2005. 22. Norrelund H, Nair KS, Jorgensen JO, et al., Diabetes, 2005;82(6):1235–43.
3. Kalantar-Zadeh K, Kopple JD, Am J Kidney Dis, 2001;38(6): 2001;50(1):96–104. 42. Kopple JD, Brunori G, Leiserowitz M, et al., Nippon Jinzo Gakkai
1343–50. 23. Fryburg DA, Barrett EJ, Diabetes Nutr Metab, 1999;12(5): Shi, 1991;33(5):468–74.
4. Mehrotra R, Kopple JD, Annu Rev Nutr, 2001;21:343–79. 329–36. 43. Kopple JD, Brunori G, Leiserowitz M, Fouque D, Nephrol Dial
5. Health Care Financing Administration: Opportunities to 24. Fryburg DA, Gelfand RA, Barrett EJ, Am J Physiol, Transplant, 2005;20(5):952–8.
Improve Care for Adult In-center Hemodialysis Patients 1991;260(3,Pt1):E499–504. 44. Schulman G, Wingard RL, Hutchison RL, et al., Am J Kidney Dis,
Report 1994. 25. Evans LM, Davies JS, Anderson RA, et al., Eur J Endocrinol, 1993;21(5):527–34.
6. Rocco MV, Paranandi L, Burrowes JD, et al., Hemodialysis, Am J 2000;142(3):254–62. 45. Iglesias P, Diez JJ, Fernandez-Reyes MJ, et al., Am J Kidney Dis,
Kidney Dis, 2002;39(2):245–56. 26. Elhadd TA, Abdu TA, Oxtoby J, et al., J Clin Endocrinol Metab, 1998;32(3):454–63.
7. Ikizler TA, Hakim RM, Kidney Int, 1996;50(2):343–57. 2001;86(9):4223–32. 46. Garibotto G, Barreca A, Russo R, et al., J Clin Invest,
8. Sharma RK, Sahu KM, J Indian Med Assoc, 27. Colao A, Di Somma C, Cuocolo A, et al., J Clin Endocrinol 1997;99(1):97–105.
2001;99(4):206–1213. Metab, 2001;86(5):1874–81. 47. Garibotto G, Barreca A, Sofia A, et al., J Am Soc Nephrol,
9. Kalantar-Zadeh K, Kopple JD, Block G, Humphreys MH, Am J 28. Kotzmann H, Riedl M, Clodi M, et al., Eur J Clin Invest, 2000;11(11):2106–13.
Kidney Dis, 2001;38(6):1251–63. 1996;26(12):1175–81. 48. Ziegler TR, Lazarus JM, Young LS, et al., J Am Soc Nephrol,
10. Lowrie EG, Lew NL, Am J Kidney Dis, 1990;15(5):458–82. 29. Golde DW, Bersch N, Li CH, Science, 1977;196(4294):1112–13. 1991;2(6):1130–35.
11. Kalantar-Zadeh K, Kilpatrick RD, Kuwae N, et al., Nephrology 30. Tonshoff B, Schaefer F, Mehls O, Pediatr Nephrol, 1990;4(6): 49. Sohmiya M, Ishikawa K, Kato Y, Eur J Endocrinol, 1998;138(3):
Dialysis Transplantation, 2005;20(9):1880–88. 654–62. 302–6.
12. Dwyer JT, Larive B, Leung J, et al., Kidney Int, 2005;68(4): 31. Blum WF, Ranke MB, Kietzmann K, Pediatr Nephrol, 50. Ericsson F, Filho JC, Lindgren BF, Scand J Urol Nephrol,
1766–76. 1991;5(4):539–44. 2004;38(4):340–47.
13. Rocco MV, Frankenfield DL, Hopson SD, McClellan WM, Ann 32. Jensen PB, Hansen TB, Oxhoj H, et al., Br J Clin Pract Suppl, 51. Feldt-Rasmussen B, Lange M, Sulowicz W, et al., J Am Soc
Intern Med, 2006;145(7):512–19. 1996;85:47–51. Nephrol, 2007; in press.
14. Cano N, Labastie-Coeyrehourq J, Lacombe P, et al., Am J Clin 33. Jensen PB, Hansen TB, Frystyk J, Clin Nephrol, 1999;52(2): 52. Jorgensen JOL, Thuesen L, Muller J, et al., Eur J Endocrinol,
Nutr, 1990;52(4):726–30. 103–9. 1994;130(3):224–8.
15. Navarro JF, Mora C, Perit Dial Int, 2001;21(1):14–24. 34. Hansen TB, Gram J, Jensen PB, et al., Clin Nephrol, 53. Hokken-Koelega AC, Stijnen T, de Muinck KS, et al., Lancet,
16. Sharma M, Rao M, Jacob S, Jacob CK, J Ren Nutr, 2002;12(4): 2000;53(2):99–107. 1991;338(8767):585–90.
229–37. 35. Jensen PB, Ekelund B, Nielsen FT, et al., Clin Nephrol, 54. Fine RN, Kohaut E, Brown D, et al., Kidney Int, 1996;49(3):
17. Hiroshige K, Sonta T, Suda T, et al., Nephrol Dial Transplant, 2000;53(1):25–32. 781–5.
2001;16(9):1856–62. 36. Johannsson G, Bengtsson BA, Ahlmen J, Am J Kidney Dis, 55. Takala J, Ruokonen E, Webster NR, et al., N Engl J Med,
18. Eustace JA, Coresh J, Kutchey C, et al., Kidney Int, 2000;57(6): 1999;33(4):709–17. 1999;341(11):785–92.
2527–38. 37. Kotzmann H, Yilmaz N, Lercher P, et al., Kidney Int, 56. Voerman BJ, Strack van Schijndel RJ, Groeneveld AB, et al.,
19. Tietze IN, Pedersen EB, Nephrol Dial Transplant, 1991;6(12): 2001;60(4):1578–85. Crit Care Med, 1995;23(4):665–73.
948–54. 38. Kotzmann H, Schmidt A, Lercher P, et al., Nephron, 57. Knox J, Demling R, Wilmore D, et al., J Trauma, 1995;39(3):
20. Acchiardo S, Moore L, Cockrell S, Effect of essential amino 2003;93(2):c75–c82. 526–30.
acids (EAA) on chronic hemodialysis (CHD) patients (PTS), Trans 39. Kotzmann H, Riedl M, Pietschmann P, et al., J Nephrol, 58. American Diabetes Association, Diabetes Care, 2006;29(Suppl.
Am Soc Artif Intern Organs, 1982;28:608–14. 2004;17(1):87–94. 1:S4–42.
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