title: Morphological and functional differences in haemostatic axis between kidney transplanted and end-stage renal disease patients.
abstract: End-stage renal disease (ESRD) is characterized by several atherothrombotic abnormalities, and kidney transplant seems to improve most of them. However, because it is not clear which mechanism is responsible for such improvement, our purpose was to clarify that point.We conducted a cross sectional study involving 30 ESRD patients, 30 ESRD kidney-transplanted patients (Ktx) and 30 healthy controls (C) to evaluate platelet morphology and function, atherothrombotic profile, endothelial abnormalities and cytokine levels involved in the insulin resistance/endothelial dysfunction. (i) Platelet morphology: The ESRD group showed platelet size similar to the other two groups (ESRD=3518x10(3)+/-549x10(3) nm2, C=3075x10(3)+/-197x10(3) nm2, Ktx=2862x10(3)+/-205x10(3) nm2) with similar platelet granules and number. (ii) Platelet surface glycoprotein: The CD41 and P-Selectin were similar between groups. (iii) Platelet intracellular calcium: Resting intracellular calcium was statistically higher in ESRD compared to the C group (ESRD=182.1+/-34.5, Ktx=126.7+/-14.1, C=72.0+/-11.0 nM, P<0.01). (iv) Hypercoagulability markers and natural anticoagulants: The Ktx and ESRD groups showed higher levels of hypercoagulability markers compared to the C group. A reduction in antithrombin activity was evident in ESRD compared to the Ktx group (P=0.03). (v) Endothelial morphology: The ESRD group showed a thickened vessel basal membrane compared to the Ktx and C groups with more endothelial sufference. (vi) Insulin resistance and pro-inflammatory cytokine profile: The ESRD showed a higher homeostasis model assessment provided equations for estimating insulin resistance (HOMA-IR) compared to the Ktx and C groups (ESRD=2.6+/-0.3, Ktx=1.8+/-0.2, C=1.1+/-0.1, P=0.005) and increased soluble tumor neurosis factor alpha (sTNFalpha) (P<0.05) and soluble vascular cell adhesion molecule (sVCAM) levels (P<0.01). Positive correlations were evident among HOMA-IR and sTNFalpha (P<0.001) and sVCAM (P=0.01), respectively. In a small subgroup of ESRD who underwent Ktx (five pts), our findings were confirmed at 1 year of follow-up, suggesting an improvement of almost haemostatic abnormalities. Kidney transplant is associated with a better atherothrombotic profile in ESRD, platelet intracellular calcium and cytokines seem to be most influenced by the transplant, while most morphological abnormalities are retained.
authors.affiliation: Department of Internal Medicine, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fiorina
authors.forename: Franco
authors.initials: F
authors.lastname: Folli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferrero
authors.forename: Elena
authors.initials: E
authors.lastname: Orsenigo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Finzi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Mazzolari
authors.forename: Claudia
authors.initials: C
authors.lastname: Placidi
authors.forename: Lucia
authors.initials: L
authors.lastname: Perego
authors.forename: Stefano
authors.initials: S
authors.lastname: La Rosa
authors.forename: Marco
authors.initials: M
authors.lastname: Melandri
authors.forename: Lucilla
authors.initials: L
authors.lastname: Monti
authors.forename: Carlo
authors.initials: C
authors.lastname: Capella
authors.forename: Armando
authors.initials: A
authors.lastname: D'Angelo
authors.forename: Carlo
authors.initials: C
authors.lastname: Staudacher
authors.forename: Antonio
authors.initials: A
authors.lastname: Secchi
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000473:pathology / Q000648:ultrastructure; D002118:Calcium / Q000097:blood; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000473:pathology; D006487:Hemostasis; D006801:Humans; D007333:Insulin Resistance; D020382:Interleukin-18 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D016030:Kidney Transplantation
chemical_list: D020382:Interleukin-18; D002118:Calcium