Fourty eight patients with cadaveric kidney allografts treated by cyclosporin A (CSA) or tacrolimus (FK506) underwent protocol graft biopsies at 1, 3 and 12 months after transplantation, and 110 biopsy specimens were obtained. Histologic diagnosis was made according to the Banff scheme. The main cause of the graft instability at 1 and 3 months was acute clinical rejection, these biopsies showed all known histological patterns of tubulointersticial and vascular rejection. Acute tubular nephropathy was found in 13% and borderline changes or nephrotoxicity in 8.7% of instable grafts. Specifically, we focused on the occurence of subclinical rejection and toxic reactions in stable renal allografts. Of these, 36.1% showed histological patterns of acute tubulointersticial and vascular rejection. The Banff score of subclinical rejection was significantly lower than in clinically apparent rejection. CSA and tacrolimus nephrotoxicity were seen in 14.2%, 19.5% and 27.2% of specimens at 1, 3 and 12 months, respectively. In over one half of the identified cases of nephrotoxicity neither increased level of immunosuppresion nor features of allograft dysfunction were found. At 12 months, 45.5% of specimens showed mild chronic transplant nephropathy and 18.1% moderate chronic transplant nephropathy. Normal morphology was found in 36.4% of biopsies. We found a high prevalence of subclinical rejection and nephrotoxicity in the studied cohort. We conclude that protocol biopsy is a reliable method in the diagnosis of clinically silent, as well as clinically apparent, disorders of the transplanted kidney.

        Key words: renal transplantation - protocol biopsy - subclinical rejection - nephrotoxicity