Для корреспонденцииЗулькарнаев Алексей Батыргараевичдоктор медицинских наук, профессор кафедры трансплантологии, нефрологии и искусственных органов факультета усовершенствования врачей ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского»,
Aim– to perform a comparative study of the long-term results of the combined use of extracorporeal photochemotherapy (photopheresis) and drug immunosuppression and standard immunosuppressive therapy in patients after kidney transplantation.Materials and methods. An open cohort randomized study was conducted, including 60 patients with chronic kidney disease stage 5D. All patients underwent single-group cadaveric kidney transplantation. Patients were randomly divided into two groups. All transplants were paired, the fi rst kidney transplant was received by the patient of the main group, the second – by comparison group. 30 patients of the main group received standard protocol of immunosuppression and 10–15 sessions of photopheresis during the fi rst six months after transplantation. All patients of the comparison group received standard immunosuppressive therapy only. End points: primary – graft loss, surrogate – the number of acute rejection episodes and infectious complications, the dynamics of creatinine blood concentration, the glomerular fi ltration rate and daily proteinuria, the dynamics of tacrolimus C0 blood concentration. To study the mechanism of photopheresis action in the late postoperative period, we evaluated the immunological parameters: subpopulation of naive T-cells (CD3+CD4+CD45RO–CD28+), the level of CD28 molecule expression (MFI) on these cells and also – subpopulation of T-regulatory cells (CD3+CD4+CD25 (Hi)CD127–).Results.The use of photopheresis leads to the graft function improvement in the late postoperative period: the creatinine concentration (p = 0.017) in the blood and daily proteinuria (p = 0.011) were lower in patients of the main group, the glomerular fi ltration rate was higher (p = 0.027). The incidence rate ratio (IRR) of rejection in the main group was signifi cantly lower than in the comparison group: 0.2509 (95% CI 0.05386, 0.9167), p = 0.0358. The risk of graft loss was also lower in the main group: IRR 0.2782 (95% CI 0.07562, 0.8657), p = 0.026, as well as the risk of infectious complications: IRR 0.3888 (95% CI 0.2754; 0, 5445), p < 0.0001. Survival rate of transplants was higher in the main group (Log Rank p = 0.009; Breslow p = 0.005). The use of photopheresis made it possible to reduce the concentration of tacrolimus in the late postoperative period (p = 0.0017) without increasing the risk of graft rejection. The photopheresis tolerogenic effect in the late postoperative period may be due to an increase in the population of T-regulatory cells with the CD3+CD4+CD25(Hi)+CD127– phenotype compared to the patients which received only standard immunosuppressive therapy (p = 0.024).Conclusion.The preventive use of photopheresis contributes to improvement of the kidney transplantation long-term outcomes. Further studies are needed to study the mechanisms of photopheresis action and markers of partial immunological tolerance to the allograft.
Despite the use of up-to-date immunosuppressive agents, graft rejection episodes are quite common and pose a serious threat to thousands of solid organ recipients. Continuous use of various combinations of immunosuppressants cause serious complications, such as arterial hypertension, post-transplant diabetes mellitus, renal failure, increased risk of infections, malignant neoplasms, etc. The attempts to achieve the desired or forced minimization of the graft immunosuppression are associated with the threat of its rejection, which makes it necessary to search for less toxic, non-medical, immunological, including cellular, management methods. One of the promising methods based on cell technology is extracorporeal photopheresis (ECP). ECP is a well-established second line therapy recommended for the prevention and treatment of refractory rejection of a heart transplant. ECP improves the pulmonary allograft functioning in patients with treatment resistant obliterating bronchiolitis syndrome. However, its value as a preventive method has not yet been established. ECP effectiveness for induction, maintenance, or anti-crisis therapy in transplantation of kidney, liver or other solid organs has been rather convincing, but the lack of randomized multicenter studies limits its use. The optimal ECP strategy has not been yet established. Nevertheless, current understanding of the pathophysiological and immunological aspects of ECP is sufficient to develop a standard methodology and technology for the procedure, as well as for a quality control system for ECP in kidney and liver transplant recipients. The review discusses possible mechanisms of the immunomodulating effect of ECP. ECP is being increasingly studied in prospective randomized trials with larger samples. This allows for an extension of its clinical indications with clear criteria, as well as for studying its multifactorial underlying immunomodulating mechanism of action. Further research is needed to identify biomarkers that could predict ECP effectiveness in solid organ transplantation.
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