Untitled - Roche Trasplantes
Untitled - Roche Trasplantes
Untitled - Roche Trasplantes
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
EARLY DIAGNOSIS OF CHRONIC ALLOGRAFT NEPHROPATHY<br />
BY MEANS OF PROTOCOL BIOPSIES<br />
early identification and treatment of CAN. Our current model of CAN also demonstrates<br />
why treatment is not a very effective strategy and why prevention of CAN has to be the<br />
goal of all transplant units.<br />
CAN is a diagnosis that has been arrived at through the pathologist’s microscope, rather<br />
than the clinic. Papers from the 1970’s through to the mid 1990’s commonly used<br />
the term “chronic rejection” to describe the clinical phenomenon of slowly and inexorably<br />
rising serum creatinine. Indeed this term can be found in papers from the<br />
past five years still loosely applied to chronic graft failure (15). It is important to understand<br />
the difference between the starting points for each of these terminologies<br />
and the consequent confusions that apply when one term is used interchangeably<br />
with the other.<br />
The term “CAN” arose from the Banff series of pathology conferences driven by such<br />
pathologists as Kim Solez, Robert Colvin, Michael Mihatsch, Daniel Serón and Lorraine<br />
Racusen (1). CAN is thus defined histologically, restricted to the renal allograft and is independent<br />
of aetiology (16). The original intent of the definition was to bring some order<br />
into the chaotic descriptions that were available for a chronically damaged allograft.<br />
Unfortunately there remains some opportunity for confusion since the underlying aetiology<br />
may also be discernable in the biopsy specimen, such as calcineurin inhibitor (CNI)<br />
nephrotoxicity and through the addition to the diagnostic features of some facets with<br />
presumed immunological aetiology. Ample opportunity to confuse has been added by<br />
those who describe pre-transplant donor renal biopsies as having CAN –clearly an absurdity.<br />
The features of CAN that are identified and scored in the Banff schema are tubular<br />
atrophy (Banff: ct) and interstitial fibrosis (Banff: ci). This should not be taken to mean<br />
that CAN is comprised of just these two appearances, nor that these are actually the<br />
most relevant to physiological, functional or prognostic indicators. It is simply that these<br />
two features are the most reliable, diffuse and easily visible changes in the biopsy, not<br />
subject to the vagaries of small samples that plague any definition relying on patchy<br />
changes in vessels or glomeruli. CAN grading from I to III simply identifies the proportion<br />
of the biopsy that is affected by these changes. It is unfortunate that the scoring of<br />
the chronic Banff “qualifiers” do not, in the current version, tie in well to the CAN grading.<br />
A revised version of the schema, with a name change to chronic sclerosing allograft<br />
nephropathy, may help us in the future. At the present time: CAN grade I requires ci1,<br />
ct1; CAN grade II requires moderate changes (ci2/ct2, or ci1/ct2, or ci2/ct1); while grade<br />
III requires severe changes (ci3/ct3, or ci2/ct3, or ci3/ct2). If there are none of the<br />
changes of “chronic rejection” such as vascular changes with disruption of the elastica,<br />
inflammatory cells in the fibrotic intima and proliferation of myofibroblasts in the intima,<br />
the grade of CAN is qualified with an “a”, but if these changes are present then<br />
it is rates “b”.<br />
17