Role of Donor Kidney Biopsies in Renal Transplantation
It is recommended that all donor kidneys should be examined by a pre-transplantation or post-perfusion biopsy. Such an examination provides a baseline with which future biopsies may be compared. Pre-existing lesions such as capillary thrombosis, arteriolosclerosis, glomerulosclerosis and interstitial fibrosis can be recorded, so that the occurrence of the same lesions in post-transplantation biopsies is not misconstrued as evidence of tacrolimus/cyclosporine toxicity or chronic allograft nephropathy. A donor kidney is mandatory in clinical settings such as an older donor (age > 55), hypertension, diabetes mellitus, acute tubular necrosis, disseminated intravascular coagulation, or unexplained rise in serum creatinine prior to death. Sometimes a biopsy becomes necessary when preliminary gross examination of the organ shows cortical scarring, renal artery atherosclerosis, or the presence of localized neoplastic nodules.
The sample of choice is a generous wedge biopsy about 1cm long and 0.5 cm in depth. The suggested size ensures that at least half the cortical zone is available for evaluation, and minimizes erroneous conclusions due to superficial subcapsular scarring secondary to senile arteriolosclerosis. Some centers prefer that both a wedge and a needle biopsy be performed to provide assurance that the deep cortex has been adequately sampled.
Urgent histologic processing of donor biopsies can be performed, when the decision on whether or not to transplant is contingent on the morphologic findings. Since prolonged cold ischemia is detrimental to long term graft function, the biopsies need to be read as soon as possible. Rapid processing protocols can yield quality permanent within 2 hours of the receipt of a specimen. Consistently providing this level of service, however, requires that both a technologist and a pathologist to be on call 24 hours a day, 7 days a week. As an alternative, a frozen section service can be offered with only the pathologist required to be on call outside of normal working hours. Frozen section morphology is adequate to recognize sclerotic glomeruli, advanced interstitial fibrosis and arteriosclerosis in the donor kidney.
Interpretation of a donor kidney biopsy calls for a semi-quantitative assessment of the degree of glomerulosclerosis, arteriosclerosis, and interstitial fibrosis present. If most of the glomeruli are patent and there is only mild arteriosclerosis and interstitial fibrosis present, the donor kidney is suitable for use. However, the extent of acceptable chronic changes within the donor kidney has not yet been rigorously defined. A widely accepted empiric rule based, in part, on a study by Gaber et al is that kidneys with greater than 20% sclerotic glomeruli not be used. At Pittsburgh, surgeons are also hesitant to use any kidney with more than mild interstitial fibrosis (greater than 25% of cortical area affected) or mild arteriosclerosis (greater than 25% luminal occlusion).
Many studies have attempted to validate the utility of donor biopsies in clinical practice by formal statistical analysis. The conclusions have not been uniform: interstitial fibrosis, glomerulosclerosis, or arteriosclerosis have variably been identified as a critical parameter in different patient populations. Glomerular, interstitial and vascular lesions are frequently (but not always) proportional to each other, and it stands to reason that advanced changes in any of the major anatomic compartments in a donor kidney should contraindicate transplantation. Yet, studies which fail to find any correlation between donor biopsy findings and post-transplantation graft function have also been published. Many of these investigations have methodological problems that include small numbers of patients, insufficient histologic detail for critical evaluation, studies limited to biopsies with only mild histologic changes, and use of only crude graft survival rates in evaluating clinical outcome.
Biopsies performed in the setting of suspected or laboratory documented disseminated intravascular coagulation need to be evaluated for the extent of microvascular injury. Organs with diffuse and extensive glomerular thrombosis should be discarded. On the other hand, the presence of scattered capillary thrombi present in a minority of glomeruli does not necessarily contraindicate transplantation. When the donor serum creatinine is normal or marginally elevated, successful transplantation has been reported. Isolated fibrin thrombi can apparently be dissolved by an intact fibrinolytic system, although this may result in a transient microangiopathic hemolytic anemia in a few instances.
Occasionally, donor biopsies will show changes consistent with glomerulonephritis. There are well documented instances of glomerulonephritis having been transmitted from donor to recipient as a result of renal transplantation. The risk is probably the highest for IgA nephropathy, a disease with high prevalence in some geographic regions. Based on isolated case reports in the literature, it would appear that mild glomerular changes in the donor biopsy can probably be ignored. Thus, modest donor derived IgA deposits do not cause significant graft dysfunction, and can spontaneously resolve with time. Similar observations have been made regarding donor transmitted membranoproliferative glomerulonephritis Type I. Focal segmental sclerosis has also been shown not to progress in the post-transplantation period.
The final indication for a donor kidney biopsy is the presence of a grossly visible nodule noticed during harvesting of the organ. When histologic examination shows a benign cyst, leiomyoma or angiomyolipoma, it is safe to proceed with transplantation. However, finding a small epithelial neoplasm can generate dilemmas that may be difficult to resolve, particularly when a high grade carcinoma is not demonstrated. The distinction between a so-called renal adenoma and a small low grade renal cell carcinoma is arbitrary, and traditionally based on the size of the lesion. If the donor lesion is small (say less than 0.5cm) and completely excised, the risk of residual or recurrent carcinoma in the recipient is probably extremely small. Dr. Israel Penn has reported 6 cases, where wide excision of the donor nodule led to an uneventful course documented by up to 186 months of post-transplantation follow up. The rare occurrence of post-transplant renal allograft carcinoma, despite the estimated 7-25% incidence (based on routine autopsy data) of small renal cell neoplasms in donor kidneys, also suggests that the use of such kidneys might be reasonable, at least in the context of informed recipient consent. Nonetheless, this is a controversial issue, and some transplant centers refuse to accept organs with small epithelial neoplasms.
1. Brunt EM, Kisson JM, Cole BR, Hanto DW. Transmission and resolution of type I membranoproliferative glomerulonephritis in recipients of cadaveric renal allografts. Transplantation 1988;46:595.