Early protocol renal allograft biopsies and graft outcome

Abstract

To evaluate whether biopsies performed early after transplantation in stable grafts can predict graft failure due to chronic transplant nephropathy, a protocol biopsy was performed at three months in 98 patients treated with antilymphocytic antibodies, cyclosporine and prednisone. Patients were followed for 58 +/- 16 months. Histological diagnosis according to the Banff schema were: normal (N = 41), borderline changes (N = 12), chronic transplant nephropathy (CTN; N = 30), CTN associated to borderline changes (N = 11) and acute rejection (N = 4). Biopsies displaying acute rejection were not considered for statistical analysis. Since clinical characteristics of patients displaying CTN either with or without tubulitis were not different, biopsies were grouped as presence or absence of CTN. Patients displaying CTN had an increased incidence of acute rejection before performing biopsy (24.3 vs. 3.9%, P = 0.003), a higher mean cyclosporine level until biopsy (242 +/- 74 vs. 214 +/- 59 ng/ml, P = 0.049) and a lower actuarial graft survival (80.5% vs. 94.4%, P = 0.024). We conclude that early protocol biopsies are useful to detect patients at risk of losing their graft due to chronic transplant nephropathy.

Serial Protocol Biopsies to Quantify the Progression of Chronic Transplant Nephropathy in Stable Renal Allografts

“…The degree of histocompatibility is a major risk factor for late renal allograft survival (26). In different studies of protocol biopsies it has been shown that acute rejection, but not histocompatibility, is a major risk factor for the early diagnosis of CAN (6,7,9,24). Thus, the present data suggest that even in rejection-free patients, the alloimmune response is determinant in the early development of intimal thickening.…”

“…Different centers have prospectively evaluated histologic renal lesions by means of protocol biopsies, showing that the early diagnosis of CAN implies a poor outcome (6,8,9,24). Recently, it has been documented in 4-month protocol biopsies that CAN associated with transplant vasculopathy implies a poorer prognosis than CAN without vessel narrowing (10).…”

“…Moreover, it has been shown that image analysis allows a very precise quantification of chronic renal damage in sirius red stained biopsies obtained from patients with different chronic nephropaties (28,29). Taking into consideration that interstitial fibrosis measured according to Banff criteria constitutes a powerful predictor of late renal allograft outcome (6,(8)(9)(10),…”

“…Donor and recipient biopsies were performed and processed for routine light microscopy as previously described (9). Briefly, tissue was embedded in paraffin, cut into 4-mm sections and stained with hematoxilin and eosin, periodic acid-Schiff, Masson's trichrome and silver methenamine.…”

“…The study of protocol biopsies has shown that CAN can be detected early after transplantation and that the presence of CAN in stable grafts is an independent predictor of allograft survival (6)(7)(8)(9). Recently, we have observed in 3-month protocol biopsies, that the presence of CAN associated with transplant vasculopathy (cv-score Ն1), implies a poorer allograft survival than CAN without vessel involvement (10).…”