Evaluation by histology, immunohistology and PCR of protocollized renal biopsies 1 week post-transplant in relation to subsequent rejection episodes

Renal biopsies were performed 1 week following renal transplantation at a time without clinical evidence of rejection in 43 patients (13 females, mean age 48 years range 18–60 and 30 males, mean age 43 years range 17–59 years). Thirty-six biopsies were available for histological or immunohistochemical analysis. Immunohistochemical analyses were performed with monoclonal antibodies against leukocytes (CD45), monocytes (WT14), complement factor 3 (C3), T-cells (Leu4), T-cell receptor αβ and γδ, tumour necrosis factor α(TNFα) IL-2 receptor (IL2-R, TAC), intercellular adhesion molecule-l (ICAMI) and HLA-DR. The slides were scored semiquantitatively with the observers having no knowledge of clinical or patient data. TNFα and IL-2R were also measured by quantative PCR. None of the studied parameters correlated to delayed graft function or graft loss. Histological analysis showed that both focal interstitial infiltrate (18/35) and tubular basement membrane disruption (11/35) were followed by a higher incidence of subsequent rejection (P = 0.03 and 0.02 respectively). Also positivity for WT14 around tubuli (P = 0.02) was associated with subsequent occurrence of rejection. The intensity of staining of ICAM-I on PTC as well as TAC on proximal tubular cells was associated with the number of subsequent rejection episodes. The association between the IL-2 receptor and subsequent rejection was also found applying PCR to the tissue specimens. We conclude that the presence of focal interstitial infiltrates and tubulitis in 1-week biopsies from well-functioning grafts carries an increased risk of subsequent rejection. The observed infiltrate outside the tubuli may consist of either monocytes or lymphocytes. Further studies, both in vitro and in vivo, applying immunohistochemical and molecular biological techniques will be necessary to further elucidate the role of adhesion molecules and interleukins in early and ongoing rejection.