Reversal of accelerated renal allograft rejection with FK 506.
Although FK 506 has been shown to effectively reverse refractory renal allograft rejection, its ability to reverse accelerated renal allograft rejection as a primary agent has not been specifically addressed. Herein evidence of the ability of FK 506 to reverse accelerated renal allograft rejection is presented. A 16-yr-old highly sensitized (PRA 75%) male underwent a second cadaveric renal transplant procedure. Despite induction immunosuppression with ATGAM, cyclosporine, azathioprine, and corticosteroids, a marked elevation in serum creatinine (1.6-->2.1 ng/dl) and reduction in urine output (4000 ml/d-->1000 ml/d) were observed on the sixth post-transplant day. Renal allograft biopsy performed at that time revealed typical features of accelerated rejection including neutrophil margination in glomerular and interstitial capillaries, and C3, IgG, and fibrin deposition in glomerular and interstitial capillaries (by immunofluorescence). FK 506 therapy was promptly instituted and ATGAM therapy discontinued. Serum creatinine peaked within 3 d of FK 506 therapy (2.5 mg/dl) and subsequently progressively dropped to 1.2 mg/dl. Repeat biopsy on FK 506 treatment day 12 revealed marked histologic improvement. Renal function remains excellent (1.3 mg/dl) 18 months after initiation of FK 506 therapy, and recurrent rejection has not been observed. This experience provides evidence that FK 506 therapy may effectively reverse accelerated renal allograft rejection, and that it provides a means for treating antibody-mediated mechanisms of allograft rejection.
Woodle
E S
ES
University of Chicago, Section of Transplantation, IL, USA.
Newell
K A
KA
Haas
M
M
Bartosh
S
S
Josephson
M A
MA
Millis
J M
JM
Bruce
D S
DS
Piper
J B
JB
Aronson
A J
AJ
Thistlethwaite
J R
JR
D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000906:Antibodies / Q000276:immunology; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D001706:Biopsy; D002102:Cadaver; D002196:Capillaries / Q000473:pathology; D003176:Complement C3 / Q000032:analysis; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D005337:Fibrin / Q000032:analysis; D005938:Glucocorticoids / Q000627:therapeutic use; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology / Q000502:physiology; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000627:therapeutic use; D009504:Neutrophils / Q000473:pathology; D012086:Reoperation; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D016055:Urinary Retention / Q000209:etiology
D000893:Anti-Inflammatory Agents; D000906:Antibodies; D000961:Antilymphocyte Serum; D003176:Complement C3; D005938:Glucocorticoids; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D008776:Methylprednisolone Hemisuccinate; D016572:Cyclosporine; D005337:Fibrin; D003404:Creatinine; D001379:Azathioprine; D016559:Tacrolimus