Research Information System
Thesis Type: Expertise In Medicine
Institution Of The Thesis: Gazi Üniversitesi, Tıp Fakültesi, Turkey
Approval Date: 2019
Thesis Language: Turkish
Student: TOLGA BAKIR
Supervisor: GALİP GÜZ
Abstract:Along with the increasing prevalence of chronic renal failure is a major problem worldwide. In patients undergoing renal transplantation after end stage renal failure, some medical problems may develop during the posttransplant period. One of these problems is avascular necrosis of the femoral head due to glucocorticoid use (AVN). Various traumatic and atraumatic factors may contribute to the etiology of osteonecrosis. A certain etiological role has been identified for some of these factors, but this is not current for risk factors. The use of glucocorticoids and excessive alcohol intake play a role in more than 80% of atraumatic cases. The pathogenesis of osteonecrosis is a controversial area. Genetic susceptibility, metabolic factors, vascular damage, increased intraosseous pressure and mechanical stress can cause osteonecrosis by affecting intraosseous blood supply. Nitric oxide (NO) is one of the most important paracrine signaling molecules in the human body. Thrombin, bradykinin, thromboxane A2, histamine, adenine nucleotides and aggregated platelets cause NO release, and the vasoconstrukation response of the vessel wall is then released as a neutral vasodilator. In addition to its vasoactive properties, nitric oxide is a potent inhibitor of platelet adhesion and aggregation. Vasoactive properties of NO also play a role in bone metabolism, inhibition of osteoclasts after mechanical stimulation and estrogen stimulation is regulated by eNOS. For all these reasons, the NO system is an important pathogenetic pathway of osteonecrosis. Bone cells have 3 main nitric oxide sentatases (eNOS, bNOS, and iNOS), eNOS predominant in osteoblastic cells. Daha önceki çalışmalarda eNOS polimorfizminin idiopatik osteonekrozis gelişimi ile ilişkili olabileceği gösterilmiştir. 218 renal transplantation volunteers who were followed in Gazi University Faculty of Medicine between 2002 and 2019 were included in the study. The pelvis of the patients with symptomatic AVN findings were diagnosed with magnetic resonance imaging (MRI). We evaluated AVN patients by considering risk factors and clinical characteristics. x Among the 218 patients included in the study between 2002 and 2019, AVN developed in the follow-up of 21 patients (9.6%). 135 of the patients were male and 83 were female. AVN was seen in 14 males (9%) and 7 (9%) of females. There was no significant difference in gender in the group without AVN (p=0.30). NOS polymorphism was detected in 16 of 21 patients in the AVN group, while in AVN group this number was 181 in 219 patients. Therefore, there was no relationship between NOS polymorphism and AVN development (p= 0.12). Cox regression analysis of sex, age, NOS polymorphism, dialysis duration, cumulative glucocorticoid dose, cnc users, mammalian Target of Rapamycin inhibitors (mTORi) and non-use cox regression analysis showed that only cyclosporine and sirolimus were independent predictive factors. Accordingly, cyclosporine use was observed to be an important independent risk factor in the development of AVN with HR: 19 [95% confidence interval 1.63-221 p <0.2]. The same situation was also observed in sirolimus users and the risk of development of AVN was determined as HR: 12.6 [95% confidence interval, 2.0-75.89 p <0.006] and sirolimus was defined as an independent risk factor. In our study, we could not find a clue that the eNOS polymorphism increased AVN in patients using glucocorticoids, but patients who used cyclosporine increased the risk of AVN by 12 times compared to those who did not use calcineurin inhibitors (CNI) and 12 patients using sirolimus compared to non-mTORi patients. ,