Gender features of hemostasis regulation in hematuria associated with nephrolithiasis

Objective. Evaluation of the gender features of the severity of hematuria that occurs during spontaneous elimination of stones from the urinary tract, and to identify receptors that modulate intracellular signaling during the development of compensatory mechanisms of platelet aggregation in women and men.

Material and methods. The study included 89 women (Group 1) and 61 men (Group 2) with nephrolithiasis, in whom hematuria was detected during examination. The activity of receptors regulating proaggregant activity of platelets was analyzed, in particular, purine P2Y-, PX1-receptors, TR-receptor, α₂-adrenoreceptor, GPVI-receptor, PAF-receptor, and adenosine A2A-receptor; agonists in concentrations EC50, causing aggregation at the level of 50% in healthy individuals, were used. Modeling of synergism of signaling pathways was reproduced by incubating platelets with subthreshold concentrations of agonists (EC10). Platelet aggregation was assessed by turbidimetric method on the ChronoLog analyzer (USA). Statistical analysis was performed using the MedCalc package.

Results. In the 1st group, severe hematuria (62,0±1,9 RBC per field) developed against the background of hyperreactivity of the PAF receptor and TR receptor, normoreactivity of the α₂-adrenoreceptor, purine P2X1 receptor, P2Y receptors, hyporeactivity of the adenosine A2 receptor and GPVI receptor. In the 2nd group, moderate microhematuria (35,9±1,9 RBC per field) was caused by hyperreactivity of the PAF receptor and TR receptor, normoreactivity of purine P2Y receptors, P2X1 receptor, adenosine A2 receptor and GPVI receptor, as well as hyporeactivity of the α₂-adrenoreceptor. Limitation of hematuria in the 1st group was ensured by the synergism of the PAF receptor, TR receptor and α₂-adrenoreceptor, in the 2nd group - PAF receptor, TR receptor and P2Y receptors. Optimal aggregation parameters in women were achieved through the interaction of signaling pathways associated with Gq and G12/13 (TR receptor) and Gi (α₂-adrenoreceptor) proteins; in men - with co-activation of signaling pathways associated with Gq, G12/13 (TR receptor) and Gq, Gi (P2Y receptors) proteins.

Conclusion. Further understanding of the mechanisms of intracellular platelet signaling associated with the GPCR receptor system will optimize the tactics of drug therapy for hematuria associated with nephrolithiasis.