Diagnostic Contribution of Renal Allograft Biopsies at Various Intervals After Transplantation

Abstract

Renal allograft biopsy is the accepted gold standard for investigating episodes of graft dysfunction in the early posttransplant period. The situation is less clear in late transplant biopsies. Later renal biopsies performed for graft dysfunction or as part of a routine investigative protocol have not been subjected to detailed critical evaluation. Two hundred sixty-three consecutive renal allograft biopsies in a single center were evaluated. They were arbitrarily divided into three groups based on interval after transplantation: group 1, up to 3 months (n=117); group 2, 4-12 months (n=60); and group 3, greater than 12 months after transplantation (n=86). There were no significant differences in demographic factors among the groups. The mean interval after transplantation was 0.8+/-0.1 months in group 1, 6.1+/-0.3 months in group 2, and 40.1+/-3.4 months in group 3. There were six principal diagnostic categories: acute rejection (AR), chronic rejection (CR), cyclosporine (CsA) nephrotoxicity, acute tubular necrosis (ATN), normal, and others. A statistically significant decrease in the frequency of AR (P<0.001) was seen in group 3 (3%) compared with groups 1 (43%) and 2 (37%). In contrast, the frequency of CR was significantly higher (P<0.001) in group 3 (71%) compared with groups 1 (0) and 2 (10%). ATN was seen almost exclusively in group 1. All but one of the 37 patients with ATN were in this group. CsA nephrotoxicity remained an important cause of graft dysfunction in all three groups, with no significant difference in incidence among the three groups. The differences between groups with other histological types were not significant. Patient management was changed based on the biopsy report in 84 patients in group 1 (72%), 45 patients in group 2 (75%), and only 16 patients in group 3 (19%) (P<0.001). In only seven patients in group 3 did the change in management result in a significant change in serum creatinine. All of these seven patients had CsA nephrotoxicity on biopsy and also had a significantly higher level of CsA compared with those with AR or CR. Thus, the diagnosis might have been possible without the need for biopsy. We conclude that late renal allograft biopsies are only rarely helpful in patient management and as such should be an investigation of last resort.

Urinary Cell mRNA Profiles and Differential Diagnosis of Acute Kidney Graft Dysfunction

“…However, our study cohort represents the vast majority of transplant recipients who present with acute allograft dysfunction. 15 External validation with the use of an independent dataset (a dataset not involved in model development) would be a robust way of showing the generalizability of our findings. Also, the study design was not conducive to determine whether the signature functions as not only a diagnostic biomarker but also, a treatment response-predictive biomarker.…”

“…15 Thus, approximately 35%-40% of biopsies done to confirm AR, are not, in fact, AR, and can potentially be avoided. Instead of the current strategy to biopsy all to confirm AR, if the physician uses the six-gene signature, then a substantial number of biopsies can be avoided without an undue number of patients with AR experiencing delayed diagnosis.…”

One-year routine renal transplant biopsies in children

“…Protocol transplant biopsies have been performed at variable intervals after transplantation, in pediatric as well as in adult recipients. CAN has been a common finding even in the early post-transplant period [2,5,6,7,8,9,10,11,12,13,14,15,16,18,19,20,21,22,23,24,25,26,27,28,29,30]. The Helsinki group found diffuse interstitial fibrosis and tubular atrophy in respectively 62% and 64% of the biopsies in patients with stable graft function 2 years after cadaveric renal transplantation.…”

“…Many centers have performed protocol renal biopsies at variable intervals in stable functioning grafts in order to evaluate the significance of acute and chronic changes [2,5,6,7,8,9,10,11,12,13,14,15,16]. In our department, protocol biopsies are performed 1 year after kidney transplantation.…”

Medullary nephritis in the diagnosis of acute cellular rejection

“…Biopsy has been an important diagnostic tool in acute rejection, which is a common complication in renal grafting, requiring immediate therapeutic management [1][2][3][4]. Acute rejection is defined as an acute deterioration in the allograft function, associated with specific pathological changes, presumed to be secondary to cell or humoral mediated immune mechanisms.…”