Untitled - Roche Trasplantes

BIOPSIA DE PROTOCOLO EN EL TRASPLANTE RENAL
The ground on which we have been able to build models of CAN is thus from histology
and not from the clinical environment. Studies of biopsies taken in an attempt to diagnose
clinical events are also uselessly misleading since they are biased by the clinical
overlay that comes with the decision to undertake the biopsy. It is thus only from protocol
biopsy studies that one can really build the conceptual models with which to test therapeutic
interventions.
Reports of long term protocol renal allograft biopsy series were scarce until the past five
years or so. The longest series was published from our group in Sydney (REF JASN 66-79)
in which 120 recipients of simultaneous pancreas and kidney transplant recipients were
biopsied at 0, 3 and 12 months and then annually thereafter to ten years. Our series, like
that from the Mayo Clinic (17) which was predominantly from living donor transplants, started
with normal kidneys from young donors and very short cold ischemia times. We had
previously published a shorter series of protocol biopsies taken from deceased donor grafts,
which thus included the impact of preceding donor disease (9,18), while others have described
the different impacts of varied immunosuppressive regimens (19-23).
Chronic allograft nephropathy is the final common pathway of different causes of renal
allograft damage. That damage may have started in the hypertensive donor or through
cold ischaemia and reperfusion injury, through acute rejection, acute or chronic CNI nephrotoxicity
and from sub-clinical rejection. It may be possible in a single biopsy to discern
the relative influences of some of these factors, but in severe cases the biopsy is as
uninformative as the “end stage kidney” that we are familiar with from native renal diseases.
Our current working model is shown in Figure 1 and described below. We believe that it
provides the foundation for understanding not only CAN, but also the relationships between
the histological appearances and the clinical perspectives (2). The new genomic
techniques for elucidating changes at the molecular level may also potentially be inculcated
into explaining the model and the early evolution of CAN.
Subclinical rejection
Fibrosis of the kidney occurs in two separate phases (68), two thirds develops quite rapidly
during the first year, with a slow and progressive accumulation beyond that time.
Interestingly the interstitial fibrosis exceeds the tubular atrophy suggesting that it is related
to more than simply the damage of tubules. The two strongest contenders for this effect
are ischaemia-reperfusion injury and acute allograft immune response –acute rejection.
In the Hannover protocol series of 258 patients (22) biopsied at 6, 12 and 16 weeks,
CAN was present in 70 (37%) and absent in 120 at 26 weeks. The significant risk factors
for CAN were receiving a deceased donor kidney, long cold ischaemia and acute rejection.
In the Westmead series acute tubular necrosis was predictive for CAN and the use
18