Deranged platelet calcium homeostasis in diabetic patients with end-stage renal failure. A possible link to increased cardiovascular mortality?
OBJECTIVE
Platelet hyperfunction is a typical feature of the prothrombotic state that frequently complicates the natural history of diabetes. In uremia, a bleeding diathesis is present, which principally involves the primary phase of hemostasis. Thus, in patients with uremia of diabetic origin, the infrequent coexistence of two opposite alterations of hemostasis takes place. In patients with uremia, an increased incidence of cardiovascular events and related mortality is observed. This phenomenon is greatly amplified in uremia of diabetic origin. Calcium homeostasis is a critical aspect of platelet function, which has recently become available in human diseases. The aim of this study was to evaluate calcium homeostasis in platelets from patients with uremia of diabetic and nondiabetic origin.


METHODS
We evaluated, by means of Fura 2, the intracellular concentration of ionized calcium ([Ca2+]i) in platelets from 18 patients with uremia of diabetic origin, 12 patients with uremia of nondiabetic origin and 16 healthy control subjects [Ca2+]i was evaluated in resting conditions and after stimulation with 0.05, 0.1, 0.5 U/ml thrombin.


RESULTS
Platelets from uremic patients with diabetes had higher resting [Ca2+]i than both control subjects (P = 0.01) and uremic patients without diabetes (P = 0.001). Similarly, after stimulation with thrombin, the absolute increase of [Ca2+]i was higher (P < 0.05) in platelets from uremic patients with diabetes compared with both control subjects and uremic patients without diabetes. The relative increase of [Ca2+]i was higher (P < 0.05) than normal in platelets from uremic patients after weak or intermediate strength thrombin. No correlation were present between [Ca2+]i values and other clinical and laboratory variables potentially associated with platelet hyperfunction.


CONCLUSIONS
Diabetes and uremia in combination further deteriorate the abnormal platelet calcium homeostasis observed in uremia.
Vicari
A M
AM
Department of Medicine, IRCCS H. San Raffaele, Milano, Italy.
Taglietti
M V
MV
Pellegatta
F
F
Spotti
D
D
Melandri
M
M
Galli
L
L
Ronchi
P
P
Folli
F
F
D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000097:blood*; D002318:Cardiovascular Diseases / Q000401:mortality*; D003928:Diabetic Nephropathies / Q000097:blood* / Q000401:mortality; D005260:Female; D006487:Hemostasis; D006706:Homeostasis; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D013917:Thrombin / Q000494:pharmacology; D014511:Uremia / Q000097:blood* / Q000401:mortality
D015415:Biomarkers; D013917:Thrombin; D002118:Calcium