title: The histopathological changes associated with allograft rejection and drug toxicity in renal transplant recipients maintained on FK506. Clinical significance and comparison with cyclosporine.
abstract: The histopathological changes in 51 renal allograft biopsies from patients immunosuppressed with FK506 were compared with those seen in 30 needle biopsies obtained from patients on cyclosporine. The frequency and severity of rejection episodes were similar in both groups. Tubular vacuolation and myocyte vacuolation were found to be useful morphological markers to monitor short-term drug toxicity associated with both drugs. Long-term administration of FK506 led to striped interstitial fibrosis and arteriolar hyalinosis, similar to that previously documented for cyclosporine. One case each of hemolytic uremic syndrome and necrotizing arteriopathy was noted in patients receiving FK506. FK506 and cyclosporine are structurally unrelated compounds; hence the parallelism observed in their nephrotoxicity profile suggests that the interactions of these drugs with renal tissue involves the operation of two different initial signal-transducing mechanisms, ultimately activating the same final metabolic pathways.
authors.affiliation: Division of Transplantation Pathology, Presbyterian University Hospital, Pittsburgh, Pennsylvania 15213.
authors.forename: P S
authors.initials: PS
authors.lastname: Randhawa
authors.forename: R
authors.initials: R
authors.lastname: Shapiro
authors.forename: M L
authors.initials: ML
authors.lastname: Jordan
authors.forename: T E
authors.initials: TE
authors.lastname: Starzl
authors.forename: A J
authors.initials: AJ
authors.lastname: Demetris
mesh_terms: D000328:Adult; D001707:Biopsy, Needle; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D005355:Fibrosis / Q000139:chemically induced; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced; D006084:Graft Rejection / Q000453:epidemiology / Q000473:pathology*; D006801:Humans; D007165:Immunosuppression Therapy; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015398:Signal Transduction; D016559:Tacrolimus / Q000009:adverse effects* / Q000627:therapeutic use*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D016572:Cyclosporine; D016559:Tacrolimus