Molecular mechanisms of elimination of upper ureteral stones

Objective. To evaluate the efficiency of lithokinetic therapy (LKT) in the localization of upper third ureteral stones and to establish the molecular mechanisms that modulate ureteral motility. Subjects and methods. The investigation was prospective and enrolled 61 patients with upper third ureteral stones. Within 7 days, the patients received standard LKT including non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics. According to the imaging control data, the patients were divided into 2 groups: 1) effective elimination of the calculus (n=40); 2) inefficient stone elimination (n=21). The activity of α2-adrenergic receptor and thromboxane A2 (TXA2) receptor was studied in vitro on platelet suspension after 24,48, and 72 hours and 7 days. Platelet aggregation was assessed by the turbidimetric method on a Chrono-Log analyzer (USA). Results. The hyperreactivity to TXA2 receptor and α2-adrenergic receptor was revealed in all the patients at the time of hospitalization. Group 1 achieved hyporeactivity to the TXA2 receptor during LKT; Group 2 failed. According to the results of modeling the risk of ineffective stone elimination, the critical activity threshold for the TXA2 receptor (TXA2-Rcrit) was >35%. Group 1 patients were also observed to have two waves of decreased α2-adrenoreceptor activity after 48 hours and 7 days; as a result, hyporeactivity to the receptor developed; in Group 2, α2-adrenergic receptor hyperreactivity persisted at all points of the study. The critical activity threshold for α2-adrenergic receptor (a.flR-Rcrit) with ineffective elimination was >52%. Conclusion. Hyperreactivity to the α2-adrenergic receptor and TXA2 receptor modulates the functional state of the ureter wall, resulting in the lower efficiency of elimination of >6-mm stones from the lumen of the upper third of the ureter during standard LKT.