Decreased intraplatelet Ca2+ release and ATP secretion in pediatric nephrotic syndrome

Platelets play an important role in the natural history of idiopathic nephr otic syndrome (NS). Although thromboembolic events are rare, the activation of circulating platelets is generally considered an important factor in th e prethrombotic state in children with NS. Platelet-activating factor (PAF) , a potent endogenous phospholipid mediator of inflammation, stimulates int racellular free calcium (Ca2+) mobilization, aggregation, and release react ions in platelets obtained from normal donors. Platelet-related effects of PAF in children with NS are unknown. We studied PAF-induced intracellular C a2+ mobilization in washed platelets and ATP secretion in platelet-rich pla sma in 34 children with idiopathic NS and in 7 healthy children. There was a significant decrease in ATP secretion: 0.021+/-0.011 mu g/10(7) cells wit h 20 nM PAF and 0.089+/-0.017 mu g/10(7) platelets with 200 nM PAF versus c ontrol values (0.195+/-0.004 mu g/10(7) and 0.813+/-0.09 mu g/10(7), respec tively). Moreover, PAF-evoked increase in intracellular free Ca2+ concentra tion was twofold lower in NS patients than in control subjects (230.1+/-22. 4 nM versus 455.6+/-15.3 nM). Also, thrombin-induced intracellular free Ca2 + mobilization was diminished in children with NS compared with the control group. Thus, contrary to expectations, a decrease of platelet reactivity i n response to PAF in vitro was observed in children with idiopathic NS. We suggest that this decreased platelet reactivity may reflect a period refrac tory to PAF and may be considered as platelet desensitization to PAF releas ed in vivo in children with NS.