genberg.qxp 31/7/07 2:39 pm Page 56
Transplantation
Figure 1: Incidence of All Types of Malignant Tumours in
patients on dialysis, high body mass index (BMI) impairs both patient and
Cadaveric Kidney Recipients Compared with the Expected
graft survival in kidney transplant recipients. In fact, a large BMI
Incidence in the General Population
mismatch between donor and recipient negatively influences the
outcome (especially when the donor has a low BMI and the recipient has
18,000
Patients
a high BMI).
23,24
n=190,046
16,000
Malignancy
14,000
As the transplanted population is getting older, malignancy is becoming
12,000
a growing concern.
25
Cancer may become the leading cause of death in
c
e (per 100,000)
organ recipients, as treatment for cardiovascular disease and infections
en
10,000
c
i
d
has improved (see Figures 1 and 2). Several studies report a significantly
8,000
higher incidence of malignancy in the transplant recipients compared
6,000
with the general population. In Australia and Sweden, a three-fold
Patients expected
umulative in 4,000
increase in the overall cancer risk has been observed.
26,27
It should be
C
noted, however, that these analyses are based on data from cohorts of
2,000
transplant recipients predominantly treated with first-generation
0
immunosuppressives. It is expected that the increasing use of
0246 810
antiproliferative agents, such as the target of rapamycin (mTOR)
Years
inhibitors sirolimus and everolimus, and the antimetabolites
mycophenolate mofetil
28
and mycophenolic acid, may have a positive
Source: Dantal J et al., 2007
25
by permission of Oxford University Press.
impact on cancer incidence. Several studies show an inhibitory effect on
tumour development
29,30
using these agents.
Donor Factors
Donor-related factors are also known to affect outcome. Donor age >65 BK Virus Nephropathy
years is correlated to poorer outcome compared with younger donor Although BK virus nephropathy (BKVN) in kidney transplants was
age.
19
(Kidneys from LDs, regardless of cold ischaemia time, HLA match, described more than 30 years ago, it was not recognised as a significant
donor age, etc., perform better than kidneys from DDs.
20
) cause of graft injury and destruction until recently.
31
Based on anecdotal
and mainly retrospective data, BKVN is estimated to cause progressively
Recipient Factors destructive nephropathy in 1–10% of kidney recipients. To date, there is
Recipient-related factors are likewise important. Although kidney no firmly established treatment, and between 10 and 30% of patients
transplantation has been shown to benefit all patients with end-stage with BKVN are reported to lose their graft within one year of diagnosis.
renal disease compared with dialysis, some patients have better long- In fact, BKVN has been suggested as being one possible explanation for
the limited improvement in long-term graft survival rate, despite the
greatly reduced incidence of acute rejection.
32
Importantly, in BKVN
patients, the necessary reduction of immunosuppression has not been
Although kidney transplantation has
associated with acute graft rejection.
33,34
Since BKV could be regarded as
been shown to benefit all patients with
being an opportunistic infection, this observation may indicate that these
patients are, in fact, over-immunosuppressed (or possibly more sensitive
end-stage renal disease compared with
to immunosuppression) compared with transplanted patients without
dialysis, some patients have better
BKVN. Consequently, this could be an important factor predisposing
them to BKVN.
long-term graft survival.
Advances in Immunosuppression
Maintenance immunosuppressive therapy over the past decade has
term graft survival. Death-censored graft survival rates are worse in the become more diversified. Until the mid-1990s, cyclosporine and
elderly. However, the most frequent cause of graft loss in the older azathioprine were the cornerstones in maintenance immunosuppressive
recipients is death with a functioning graft, not actual graft loss. In therapy. Today, these agents have been largely replaced by the newer
fact, patient death because of cardiovascular disease is one of the agents tacrolimus and mycophenolate mofetil. Triple immuno-
most important causes of graft loss overall. Consequently, risk factors suppression continues to be the standard, and corticosteroids are still
for cardiovascular disease, such as hypertension, hyperlipidaemia part of most widely used immunosuppressive protocols. More effective
and diabetes mellitus, are also risk factors for impaired long-term immunosuppression has reduced the incidence of acute rejection
graft survival.
21,22
without a reduction in patient survival. The calcineurin inhibitors
(CNIs) still remain the most important immunosuppressive drugs
Furthermore, in a large, retrospective analysis of >70,000 patients in transplantation.
35
transplanted between 1988 and 1997, both graft and patient survival
rates were decreased in recipients who had been treated with dialysis for In terms of drug development, sirolimus (Rapamune
®
, registered in 2001)
>12 months prior to transplantation. Not surprisingly, pre-emptive is the latest conceptually new drug for maintenance immunosuppression
transplantation reduced the rate of graft loss. In contrast to data for to reach the market. The promising agents FTY720 or fingolimod
56 EUROPEAN RENAL DISEASE 2007
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