Untitled - Roche Trasplantes
Untitled - Roche Trasplantes
Untitled - Roche Trasplantes
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EARLY DIAGNOSIS OF CHRONIC ALLOGRAFT NEPHROPATHY<br />
BY MEANS OF PROTOCOL BIOPSIES<br />
anti-Il2 receptor antibody (51). An alternative strategy has been studied since the early<br />
1980’s, notably early conversion from a calcineurin inhibitor based regimen to one which<br />
eliminates the CNI after three, six or twelve months. It is not in the scope of this chapter<br />
to identify and review these studies which others have accomplished in formal metaanalyses<br />
(52, 53), but it is important to note that one of the more recent studies using<br />
sirolimus and corticosteroids as maintenance therapy was accompanied by protocol<br />
biopsies (54). In this study biopsies at implantation, 12 and 36 months were studied in<br />
a subset of patients that provided biopsy material at each time point. The most interesting<br />
feature of this study was that the group in which the CNI was eliminated had<br />
resolution of tubular atrophy between 12 and 36 months, without increased interstitial<br />
fibrosis. Thus the total CADI index of chronic damage was unchanged in the sirolimus<br />
treated patients, suggesting that the strategy might hold out some hopes for long term<br />
improvement in CAN, if effective and applicable clinical regimens can be developed to<br />
avoid the CNI’s.<br />
Future opportunities<br />
Clearly, very early diagnosis of events that may subsequently damage the graft might<br />
increase the effectiveness of interventions. The possibility that gene events will predict<br />
histology has been borne out in early studies from a number of groups including our<br />
own. Vitalone at the World Transplant Congress in Boston in July 2006 (55), presented<br />
data derived from Gene Microarrays demonstrating that genes associated with both<br />
CAN and rejection “turn on” –i.e., produce mRNA– earlier than the histological changes<br />
were apparent. If this is borne out in other laboratories and in other series of patients,<br />
it may offer a way of predicting the patients in whom intervention would be especially<br />
valuable.<br />
SUMMARY<br />
Chronic Allograft Nephropathy is the syndrome that has come to plague renal transplantation<br />
as the cause of most graft losses. It has been evident for as long as we have been<br />
transplanting the kidney, but in the early days it was overshadowed by acute rejection<br />
and mis-interpreted as an entirely immune related phenomenon termed “chronic rejection”.<br />
It has been the source of most concern to clinical transplant programs for the past<br />
ten years, but the long term nature of the syndrome has meant that it has not been an<br />
easy target for research. Paradoxically, the pharmaceutical industry –which has the most<br />
to gain from long term use of particular agents– is most unlikely to fund the research trials<br />
that we will need to prove which are the best treatment options. Long term investments<br />
in this area are likely to be superseded before they have produced any answers. We are<br />
thus left with the individual transplant centre studies, implied answers from long term<br />
cohort studies using older pharmaceutical agents and new molecular genomic and proteomic<br />
technologies that have yet to deliver on their promise.<br />
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