Apoptosis in the human allografted kidney. Analysis by terminal deoxynucleotidyl transferase-mediated DUTP-botin nick...

Apoptosis is a distinct form of cell death and occurs under a variety of physiological and pathological conditions. This study was conducted to examine the occurrence of apoptotic cell death in 44 formalin-fixed, paraffin-embedded biopsy specimens from allografted kidneys by the terminal deoxynucleiotidyl transferase (TdT)-mediated D-UTP-biotin nick end labeling (TUNEL) method. Careful observation of routine hematoxylin and eosin sections revealed a few apoptotic cells in cortical tubules. TUNEL signal was detected variably in tubular epithelia, and occasionally in lymphocytic cells and endothelium. The number of tubular epithelia demonstrating TUNEL signals was highest for cyclosporine tubulopathy, followed by acute rejection of very mild or mild grade, and then by chronic allograft nephropathy. Protocol biopsies from normally functioning grafts showed the least apoptotic cells, with the number being significantly lower than that of both cyclosporine tubulopathy (P < 0.01) and acute rejection (P < 0.05). Two specimens of acute accelerated rejection with diffuse hemorrhagic necrosis showed nonspecific signals in a few epithelia. These findings suggest that acute rejection or cyclosporine nephropathy not infrequently induces apoptosis of tubular epithelia, which might lead to tubular atrophy or loss, resulting in chronic transplant nephropathy.