edited_Hricik_edit-2.qxp 14/7/09 10:15 Page 76
Transplantation
transplantation, lumbar bone density declined in both groups and there It remains concerning that, in contrast to the excellent outcomes
was no significant difference after three months.
24
On the other hand, in a reported in many uncontrolled studies, results from recent randomized
large, non-randomized, single-center experience with early corticosteroid trials continue to show a greater risk for acute rejection in patients who
withdrawal the long-term incidence of fractures and avascular necrosis stop corticosteroids. The long-term outcomes of this minority of
was significantly lower than that observed in a historical group,
8
a finding patients warrant further study. Hints of increased rates of long-term
that was confirmed after five years of follow-up in the Astellas study.
12
graft fibrosis in some of the recently published trials also warrant
concern, raising the question of whether corticosteroids may protect
The wisdom of withdrawing high-risk patients from corticosteroids against the development of fibrosis mediated by CNIs or other
remains controversial. Highly sensitized patients
12,17,25
and African- mechanisms. The wisdom of withdrawing corticosteroids from patients
Americans
26
have been excluded from some recent trials involving perceived to be at high risk of immune injury (e.g. highly sensitized
corticosteroid-free immunosuppression. African-Americans appear to patients or African-Americans) remains controversial.
have a disproportionate risk for acute and subclinical rejection after
corticosteroid withdrawal.
27,28
However, an aggressive approach to Finally, results from recent trials raise serious questions about the
recognizing and treating subclinical acute rejection may result in long- metabolic and cardiovascular benefits associated with complete
term outcomes that are comparable to those seen in non-African- elimination of corticosteroids, at least compared with those achieved
Americans.
28
In the Astellas Steroid Withdrawal Study there was no with the low doses of corticosteroids now commonly used in practice.
difference in the cumulative incidence of acute rejection based on For a minority of kidney transplant recipients, these negligible benefits
ethnicity.
12
However, African-American ethnicity increased the risk of may be outweighed by a risk for acute or chronic allograft injury that
graft loss (relative risk 4.3; p=0.008), suggesting the possibility of may be precipitated by elimination of corticosteroids. ■
unrecognized subclinical rejection in these patients. Based on our
recent findings, which suggest a correlation between hemodialysis
Joshua J Augustine, MD, is an Assistant Professor of Medicine at Case Western Reserve
exposure and T-cell alloreactivity,
29
longer dialysis vintage may also be a
University and University Hospitals Case Medical Center. His research interests include the
risk factor for corticosteroid elimination. Immune monitoring techniques study of proteinuria in kidney transplant recipients, other complications of
may help to individualize corticosteroid therapy, with the goal of
immunosuppression, and immune risk assessment in transplant recipients. Dr Augustine
trained in general nephrology at the Cleveland Clinic Foundation and in transplant
identifying a minority of high-risk patients and excluding them from
nephrology at University Hospitals Case Medical Center, and received undergraduate and
corticosteroid withdrawal. medical degrees from the University of Michigan.
In summary, the results of a number of studies published during the past
Kenneth A Bodziak, MD, is an Assistant Professor of Medicine at Case Western Reserve
University and University Hospitals Case Medical Center. He has interests in both general
15 years indicate that the majority of kidney transplant recipients can
and transplant nephrology, with research interests focused on optimal immunosuppressive
safely undergo corticosteroid elimination when concomitantly treated regimens for kidney transplant recipients. Dr Bodziak trained in general nephrology at the
with a CNI and MMF. In fact, data from the most recent report of the
University of Colorado Health Science Center and in transplant nephrology at the Oregon
Health Science Center University Hospital. He received his medical degree from the
Scientific Registry for Transplant Recipients indicate that elimination of
University of Cincinnati.
corticosteroids has increasingly become the standard of practice at
many transplant centers (see Figure 2).
30
As of 2006, over 30% of
Donald E Hricik, MD, is a Professor of Medicine at Case Western Reserve University. He is
patients receiving kidney transplants in the US are discharged from their also Chief of the Division of Nephrology and Hypertension and Medical Director of the
initial hospitalization without maintenance corticosteroid therapy. This
Transplantation Service at University Hospitals Case Medical Center. Dr Hricik also serves
as the Postgraduate Education Director for the American Society of Transplantation. His
pattern of practice reflects the paradigm shift towards earlier
research interests have focused on immune monitoring after kidney transplantation and
corticosteroid withdrawal or even corticosteroid avoidance that has the development of new combinations of immunosuppressive drug therapies. Dr Hricik
permeated recent clinical trials. Induction antibody therapy appears to
received his medical degree from Georgetown University.
improve outcomes after early corticosteroid withdrawal.
1. Hollenberg SM, Evans RM, Cell, 1988;55:899–906. 2009;9:160–68. 21. Gallon LG, Winoto J, Leventhal JR, et al., Clin J Am Soc Nephrol,
2. Ray A, Prefontaine KE, Proc Natl Acad Sci U S A, 1994;91: 12. Woodle ES, First MR, Pirsch J, et al., Ann Surg, 2006;1:1029–38.
752–6. 2008;248:564–77. 22. Pascual J, van Hooff JP, Salmela K, et al., Transplantation,
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1995;15:943–53. 2005;137:364–73. 23. Maalouf NM, Shane E, J Clin Endocrinol Metab,
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2003;8:160–66. Transplantation, 2006;82(Suppl. 3):322. 24. ter Meulen CG, van Riemsdijk I, Hene RJ, et al., Transplantation,
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1080–89. Transplant, 2007;7(Suppl. 2):263. 25. Vincenti F, Monaco A, Grinyo J, et al., Am J Transplant,
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2001;72:845-850. 2008;8:307–16. 26. Woodle ES, Vincenti F, Lorber MI, et al., Am J Transplant,
7. Birkeland Transplantation, 1998;66:1207–10. 17. Vitko S, Klinger M, Salmela K, et al., Transplantation, 2005:5:157–66.
8. Matas AJ, Kandaswamy R, Gillingham KJ, et al., Am J 2005;80:1734–41. 27. Ahsan N, Hricik D, Matas A, et al., Transplantation,
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9. Kaufman DB, Leventhal JR, Axelrod D, et al., Am J Transplant, Transpl Int, 2003;16:82–7. 28. Kumar MS, Moritz MJ, Saaed MI, et al., Am J Transplant,
2005;5:2539–48. 19. Kumar MS, Heifets M, Moritz MJ, et al., Transplantation, 2005;5:1976–85.
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76 US NEPHROLOGY
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