Eurotransplant Senior DR-compatible Program

The current *Eurotransplant Senior Program* allocates kidneys from older
donors(at least 65 year), without prospective matching for HLA antigens, to
older (at least 65 years) local transplant candidates (13). The ESP program was
introduced in 1999 and has resulted in a significant increase in availability
of kideney older donors for transplantation and consequentely more elderly
dialysis patients have placed on the kidney waiting list. Besides these
advantages, several studies have documented higher acute rejection rates in
recipients of kideney fron older donors, independent of the age category of the
recipients. It is conceivable that prophylactic treatment with anti-lymphocyte
antibodies attenuates the interaction between renal aging changes,
ischemia-reperfusion injury and the ensuing immune response. Thus, at least
theoretically, it should be possible to improve the outcome of older donor
kidneys in young recipients by providing more intensive immune suppression in
the early post-operative period in order to prevent excess rejection rates.
Such an approach may be acceptable for younger recipients, but remains to be
determined for the elderly. The therapeutic index for clinical immune
suppression appears to be even narrower in the elderly than in younger renal
transplant recipients.
In the elderly, cardiovascular and especially infectious causes are among the
leading primary causes of death. There is no doubt that extra boluses of
steroids, recycling of the steroid taper or treatment with poly- or monoclonal
antibodies add significantly to post-transplant morbidity and mortality.
We propose that introduction of prospective matching for HLA-DR antigens in the
context of Old-for-Old allocation may result in less acute rejection episodes,
better preservation of renal function as well as less infectious cause
morbidity and mortality.

Reduce acute rejection rates in the Old-for-Old kidney transplantation program.
Less acute rejection in these vulnerable older kidneys inevitable translates in
better initial kidney function. Less need for acute rejection treatments with
high dose intravenous steroids and/or polyclonal anti T-cell antibodies will
allso reduce to incidence of inctious cause mortality, the leading cause of
death in the elderly transplant recipient.

Observational, prospective, randomized multicenter allocation study to compare
the impact of prospective matching for HLA-DR antigens between donor and
recipient on outcome parameters in the Eurotransplant Senior Program (ESP).
Paired kidneys from 300 donors >= 65 year of age will be randomized at the
center or (cooperating) regional level: the first kidney according to current
ESP allocation (waiting time, no prospective matching for HLA antigens) and the
contra-lateral kidney aimed at zero mismatches for HLA-DR followed by waiting
time. Cold ischemia times should be as short as possible, but always under 20
hours.
In the participating centers recipients will be treated with an evidence-based
standardized immunosuppressive regimen. This regimen is already standard
therapy in the large majority of transplant centers and its superior efficacy
has been documented in the largest prospective study in de novo trenal
transplant recipients to date.

This is an observational allocation study and there is no additional burden
associated with participation. The proposed HLA matching will, according to all
medical knowledge, not negatively but rather positively influence the outcome
of the selected patients. Treatment regimens and outpatient department visits
are according to (evidence-based) standard medical care for renal transplant
recipients and their follow-up. The amount and number of blood samples,
physical examinations or other tests are the same in both groups and according
to current standard care after renal transplantation.