Ex vivo microvesicle formation after prolonged ischemia in renal transplantation.
BACKGROUND
Patients with chronic renal failure suffer from dysfunction in coagulation. Kidney transplantation induces inflammatory reactions and thus activation of platelets. Activated platelets, in turn, form microvesicles by shedding. These microvesicles have been shown to have coagulant activities. Activated platelets in prolonged cold ischemia were associated with delayed graft function and inferior survival. We investigated ex vivo formation of microvesicles in kidney transplantation and the influence of cold graft storage on microvesicles.


METHODS
20 patients (47.4+/-10.6 years (mean+/-SD)) undergoing transplantation were included in the study after written informed consent. Dependent on cold preservation time of transplanted kidneys, recipients were allocated into two groups with 10.4+/-6.1 h (group 1) and 23.7+/-3.8 h (group 2) preservation time, respectively. Blood samples were drawn before anesthesia, 12 h, 2, 7 and 14 days after transplantation. To evaluate microvesicle release, samples were activated with thrombin-receptor-activating-peptide-6 (TRAP) or adenosine-di-phosphate. Microvesicles were counted as percentage of platelets smaller than a predetermined size in flow cytometry.


RESULTS
Platelet derived ex vivo microvesicle formation was significantly higher up to 48 h after transplantation when stimulated with TRAP in group 1. Platelet count was significantly higher compared to baseline values in the short-term ischemia group but not with long-term ischemia. Creatinine was significantly lower at study end compared to baseline with no differences between both groups.


CONCLUSIONS
Lower platelet microvesicle formation after ex vivo stimulation with TRAP was associated with longer graft ischemia time. This may be a sign of former activation of platelets which could influence graft function and survival.
Schuerholz
Tobias
T
Clinic of Anesthesiology and Intensive Care, Friedrich-Schiller-University, Erlanger Allee 101, D-07747 Jena, Germany. tobias.schuerholz@med.uni-jena.de
Weissig
Annette
A
Juettner
Bjoern
B
Becker
Thomas
T
Scheinichen
Dirk
D
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology; D003080:Cold Temperature; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009926:Organ Preservation; D010446:Peptide Fragments / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D013997:Time Factors
D010446:Peptide Fragments; C082835:thrombin receptor peptide (42-47); D000244:Adenosine Diphosphate