Inhibitors of ADAMTS13: a potential factor in the cause of thrombotic microangiopathy in a renal allograft recipient.
BACKGROUND
Thrombotic microangiopathy (TMA) is a well-known complication after renal allograft transplantation. In most cases, calcineurin inhibitor is believed to play a role in the development of this disorder. Recent studies have shown that a deficiency in the activity of the von Willebrand factor-cleaving metalloprotease ADAMTS13 causes thrombotic thrombocytopenic purpura. A similar mechanism occurring in patients who develop TMA after renal transplantation has not been described.


METHODS
Analysis of plasma samples from a patient who developed TMA after receiving a cadaveric renal allograft revealed undetectable ADAMTS13 activity and the presence of its inhibitors.


RESULTS
Discontinuation of cyclosporine and daily plasma exchange increased the ADAMTS13 activity, which was followed by resolution of the microangiopathic hemolysis and improvement of the graft function. At 3-month follow-up, the ADAMTS13 activity remained in the normal range and no inhibitors were detected.


CONCLUSIONS
This is the first case to demonstrate a correlation between the presence of ADAMTS13 inhibitors and transplant-associated TMA. Autoimmune inhibitors of ADAMTS13 should be considered in patients with transplant-associated thrombotic microangiopathy. The role of calcineurin inhibitor in the formation of autoantibodies to ADAMTS13 remains to be explored.
Pham
Phuong-Thu T
PT
Division of Nephrology, Kidney and Pancreas Transplantation, Department of Medicine, UCLA Medical Center, University of California at Los Angeles, 7-155 Factor Building, 10833 LeConte Avenue, Los Angeles, CA 90095, USA. ppham@mednet.ucla.edu.
Danovitch
Gabriel M
GM
Wilkinson
Alan H
AH
Gritsch
H Albin
HA
Pham
Phuong-Chi T
PC
Eric
Tong M
TM
Kendrick
Elizabeth
E
Charles
Lassman R
LR
Tsai
Han-Mou
HM
D016572:Cyclosporine / Q000009:adverse effects; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000601:surgery; D016030:Kidney Transplantation; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*; D008833:Microcirculation; D008875:Middle Aged; D010951:Plasma Exchange; D010976:Platelet Count; D013927:Thrombosis / Q000139:chemically induced* / Q000201:enzymology* / Q000628:therapy; D014184:Transplantation, Homologous; D014841:von Willebrand Factor / Q000378:metabolism
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D014841:von Willebrand Factor; D016572:Cyclosporine; D008666:Metalloendopeptidases