Untitled - Roche Trasplantes

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EARLY DIAGNOSIS OF CHRONIC ALLOGRAFT NEPHROPATHY BY MEANS OF PROTOCOL BIOPSIES J. Chapman ROLE OF PROTOCOL BIOPSY EARLY AFTER TRANSPLANTATION The term “protocol biopsy” implies, in the context of renal transplantation, that biopsy is undertaken as a result of a pre-determined protocol and not because of a clinical event that has lead to the “need” for biopsy. The two processes have lead to very different answers over the years of development of renal transplantation. The clinically driven biopsy leads to a self-perpetuating result. Since biopsy is only performed at times of renal dysfunction, the results lead to the ability to distinguish between different causes of dysfunction –which essentially means distinguishing types of acute rejection from each other and from acute calcineurin inhibitor toxicity, or rare cases of pyelonephritis or vascular catastrophe. The clinically driven biopsy has not allowed distinction between the appearance of the kidney in times of acute dysfunction and times of stable function. It has been illuminating, and still remains surprising to some, that the histological data derived from protocol biopsies taken at times of stable function show a similar range of appearances to clinical biopsies. It has also required protocol biopsies to understand that the functional changes in renal allografts dramatically underestimate the severity of the pathological damage. This chapter reviews the principles upon which the data are accrued from renal allograft biopsies specifically to understand the evolution of chronic allograft nephropathy (1, 2). It is possible to use these data to build and then test a model for understanding the pa- 13
BIOPSIA DE PROTOCOLO EN EL TRASPLANTE RENAL thophysiology of chronic destruction of the renal transplant and the linkage between the underlying pathology and the observed functional changes. THE RISK OF GRAFT COMPLICATIONS In order to justify the use of protocol or surveillance percutaneous needle-core biopsies they must yield a low risk of complications including graft loss and morbidity such as admission to hospital and hemorrhage. A variety of reports of the risk of major complications including substantial bleeding, macroscopic hematuria with ureteric obstruction, peritonitis or graft loss is approximately 1% (3-5). Minor complication include macroscopic hematuria in 3.5%, perirenal hematomas 2.5%, asymptomatic arterio-venous fistulas 7.3% and vasovagal reactions 0.5% (5). Loss of the graft after protocol biopsy is in the region of 0.03%, based on various reports where the losses are recorded as: 0 from 2,127 biopsies (4), 1 from 1,171 (5), 0 of 328 (6), 0 from 1,037 (3), 0 from 961 biopsies (7), 0 from 277 (8), and 1 from 151 (9). The risk of renal allograft biopsy is increased when needles larger that 18G are used (6); when the biopsy is undertaken for clinical indications (presumably because the indication demands higher risks, or the graft is essentially unstable prior to the biopsy); and when the kidney is in an intraperitoneal position. Safety of protocol biopsies should thus be maximized through use of a skilled operator; mandatory ultrasound guidance immediately prior to biopsy to identify any unsuspected lesions such as urinary obstruction or an arterio-venous fistula; and use of an automated spring loaded gun mechanism rather than a manual cannula and trocar. Some operators suggest the use of a 16-gauge needle (10) and a single pass, rather than the 18-gauge needle favoured by many units but with more than one needle core sample (5). Certain exclusion criteria are also required to ensure that inappropriate risks are not taken. Table I details inclusion and exclusion criteria that should be considered prior to protocol biopsy. It would be appropriate for all of the inclusion criteria to be required to be met, but exclusion should require only a single criterion to be met. This is a conservative position designed to reduce the morbidity of the procedure undertaken with a lower yield of therapeutic decision making than occurs with acute clinically indicated biopsies. In particular, the use of ultrasound not only localises the kidney accurately, but also identifies potential sources of complication, the commonest of which is partial ureteric obstruction. RELIABILITY OF PROTOCOL HISTOLOGY RESULTS How good is the biopsy as a sample of the kidney? The reliability of a given result is related to the amount of tissue obtained and to the variability if the histological finding within the kidney. Clearly very patchy events are seen with less reliability than homogeneous 14
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