Molecular mechanisms of elimination of upper ureteral stones

DOI: https://doi.org/10.29296/25877305-2022-06-10
Issue: 
6
Year: 
2022

Professor E. Barinov, MD; Yu. Malinin, Candidate of Medical Sciences;
Kh. Grigoryan, Candidate of Medical Sciences
M. Gorky Donetsk National Medical University, Donetsk, Donetsk People's Republic

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 (α2AR-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.

Keywords: 
nephrology
nephrolithiasis
lithokinetic therapy
ureteral motility
α2-adrenergic receptor
TXA2 receptor



References: 
  1. Shen H., Chen Z., Mokhtar A.D. еt al. Expression of β-adrenergic receptor subtypes in human normal and dilated ureter. Int Urol Nephrol. 2017; 49 (10): 1771–8. DOI: 10.1007/s11255-017-1667-y
  2. Guan N.N., Gustafsson L.E., Svennersten K. Inhibitory Effects of Urothelium-related Factors. Basic Clin Pharmacol Toxicol. 2017; 121 (4): 220–4. DOI: 10.1111/bcpt.12785
  3. Skolarikos A., Grivas N., Kallidonis P. Members of RISTA Study Group. The Efficacy of Medical Expulsive Therapy (MET) in Improving Stone-free Rate and Stone Expulsion Time, After Extracorporeal Shock Wave Lithotripsy (SWL) for Upper Urinary Stones: A Systematic Review and Meta-analysis. Urology. 2015; 86 (6): 1057–64. DOI: 10.1016/j.urology.2015.09.004
  4. Sairam K. Should we SUSPEND MET? Not really. Cent Eur J Urol. 2016; 69 (2): 183. DOI: 10.5173/ceju.2016.864
  5. Campschroer T., Zhu X., Vernooij R.W.M. et al. α-Blockers as medical expulsive therapy for ureteric stones: a Cochrane systematic review. BJU Int. 2018; 122 (6): 932–45. DOI: 10.1111/bju.14454
  6. Liyan Xu, Yan W. Combined influence of ABCB1 genetic polymorphism and DNA methylation on aspirin resistance in Chinese ischemic stroke patients. Acta Neurol Belg. 2021Online ahead of print. DOI: 10.1007/s13760-021-01714-1
  7. Al-Sofiani M.E., Yanek L.R., Faraday N. еt al. Diabetes and Platelet Response to Low-Dose Aspirin. J Clin Endocrinol Metab. 2018; 103 (12): 4599–608. DOI: 10.1210/jc.2018-01254
  8. Chaignat V., Danuser H., Stoffel M.H. еt al. Effects of a non-selective COX inhibitor and selective COX-2 inhibitors on contractility of human and porcine ureters in vitro and in vivo. Br J Pharmacol. 2008; 154 (6): 1297–307. DOI: 10.1038/bjp.2008.193
  9. Nørregaard R., Jensen B.L., Topcu S.O. еt al. Cyclooxygenase type 2 is increased in obstructed rat and human ureter and contributes to pelvic pressure increase after obstruction. Kidney Int. 2006; 70 (5): 872–81. DOI: 10.1038/sj.ki.5001616
  10. Lee S.Y., Lee M.Y., Park S.H. et al. NS-398 (a selective cyclooxygenase-2 inhibitor) decreases agonist-induced contraction of the human ureter via calcium channel inhibition. J Endourol. 2010; 24 (11): 1863–8. DOI: 10.1089/end.2009.0461
  11. Wang H., Sun X., Dong W. еt al. Association of GPIa and COX-2 gene polymorphism with aspirin resistance. J Clin Lab Anal. 2018; 32 (4): e22331. DOI: 10.1002/jcla.22331
  12. Jerde T.J., Calamon-Dixon J.L., Bjorling D.E. et al. Celecoxib inhibits ureteral contractility and prostanoid release. Urology. 2005; 65 (1): 185–90. DOI: 10.1016/j.urology.2004.08.057
  13. Huang Z.A., Scotland K.B., Li Y. еt al. Determination of urinary prostaglandin E2 as a potential biomarker of ureteral stent associated inflammation. J Chromatogr B Analyt Technol Biomed Life Sci. 2020; 1145: 122107. DOI: 10.1016/j.jchromb.2020.122107
  14. Luo R., Kakizoe Y., Wang F. еt al. Deficiency of mPGES-1 exacerbates renal fibrosis and inflammation in mice with unilateral ureteral obstruction. Am J Physiol Renal Physiol. 2017; 312 (1): F121-F133. DOI: 10.1152/ajprenal.00231.2016
  15. Motiejunaite J., Amar L., Vidal-Petiot E. Adrenergic receptors and cardiovascular effects of catecholamines. Ann Endocrinol (Paris). 2021; 82 (3-4): 193–7. DOI: 10.1016/j.ando.2020.03.012
  16. Monks D.R., Bund S.J. The modulation of ureteral smooth muscle contractile responses by α1- and α2-adrenoceptor activation. Physiol Int. 2018; 105 (3): 225–32. DOI: 10.1556/2060.105.2018.3.19
  17. Hering L., Rahman M., Hoch H. еt al. α2A-Adrenoceptors Modulate Renal Sympathetic Neurotransmission and Protect against Hypertensive Kidney Disease. J Am Soc Nephrol. 2020; 31 (4): 783–98. DOI: 10.1681/ASN.2019060599
  18. Park Y.C., Tomiyama Y., Hayakawa K. еt al. Existence of a beta3-adrenoceptro and its functional role in the human ureter. J Urol. 2000; 164 (4): 1364–70.