Immunological Disorders and Their Correction in Patients with Terminal Stage Chronic Renal Failure (CSR) Before and After Allogeneic Kidney Transplantation

The dissertation is dedicated to the study of immunological disorders and their correction in patients with terminal stage chronic renal failure before and after allogeneic kidney transplantation. The work analyzes immunological parameters of patients receiving various replacement therapy modalities, including traditional hemodialysis, program hemodialysis supplemented with ozone therapy, and the post-transplantation period, considering genetic blood markers and treatment duration. A computer program for optimizing standard immunosuppressive therapy has been developed.

RELEVANCE OF THE RESEARCH. Terminal chronic renal failure is the outcome of most chronic kidney diseases [17, 23, 29, 55, 67, 68, 80, 93, 126, 127, 144, 145, 148, 156, 171, 220]. Data on the prevalence of CKD are highly contradictory and the number of patients with CKD fluctuates significantly [9, 42, 43, 87, 95, 96, 98, 121, 127, 140, 150, 195, 205, 223, 225, 229, 247, 251, 277]. The problem of comprehensive treatment of patients with terminal stage CKD remains one of the most relevant and largely unresolved problems of therapy, pediatrics, and surgery [11, 17, 23, 29, 54, 55, 67, 68, 80, 87, 92, 93, 126, 127, 144, 145, 148, 156, 171, 220].

To eliminate endogenous intoxication in terminal stage CKD, a number of modern comprehensive treatment methods have been proposed, such as hemodialysis [27, 28, 32, 41, 49, 65, 81, 90, 93, 141, 142, 145, 167, 200], various variants of peritoneal dialysis [5, 27, 66, 145, 149, 200], extracorporeal detoxification of the organism [27, 130, 200], oxygen impact methods — ozone therapy [3, 13, 14, 35, 73, 74, 76, 79, 94, 97, 99, 103, 114, 136, 155, 217, 230, 250], and kidney transplantation [21, 23, 109, 117, 156, 171, 220, 263], which have significantly improved treatment outcomes [29, 99].

It has been proven that one of the pathogenetic symptoms of terminal stage CKD is secondary immunodeficiency, in the development of which immunological reactivity plays an important role [4, 12, 16, 33, 38, 40, 46, 53, 57, 64, 93, 100, 107, 108, 112, 127, 129, 131, 134, 143, 147, 160, 173]. However, insufficient attention is paid to problems of immunological shifts in the organism in terminal stage CKD: schemes for the correction of immunological disorders in terminal stage CKD in the pre- and postoperative periods of kidney transplantation have not been developed, although the expediency and necessity of using immunomodulators in the treatment of patients with chronic diseases is considered proven [16, 38, 46, 57, 91, 129, 143, 152]. Moreover, the use of immunomodulators in surgical patients to stimulate functional mechanisms and correct secondary immunodeficiencies is one of the promising directions for enhancing the immunological protection of the organism in the prevention and treatment of infectious complications [34, 47, 160, 178]. In the clinic of hospital surgery of the Voronezh State Medical Academy named after N.N. Burdenko, methods of ozone therapy for various surgical diseases have been developed and implemented in clinical practice for a number of years. Studies conducted in the clinic have demonstrated the pathogenetic rationale for the use of ozone solutions for topical, parenteral, and intestinal therapy in surgical pathology. At the same time, the question of the influence of ozone therapy in the comprehensive treatment of patients with terminal stage CKD receiving replacement therapy remains insufficiently studied. In this regard, our attention was attracted by the use of ozone solutions in patients on hemodialysis.

RESEARCH OBJECTIVE: to improve the outcomes of comprehensive treatment of patients with terminal stage chronic renal failure before and after allogeneic kidney transplantation by selecting and optimizing immunocorrective therapy.

RESEARCH TASKS:

1. To identify typical immunological reactions in patients with terminal stage CKD on PGD with establishing key parameters and formulas of immunological disorders.

2. To evaluate typical immunological reactions in patients with terminal stage CKD receiving replacement therapy depending on the duration of treatment with establishing key parameters and formulas of immunological disorders.

3. To establish typical immunological reactions in patients with terminal stage CKD after allogeneic kidney transplantation depending on blood genetic markers with identifying key parameters and formulas of immunocorrection targets.

4. To characterize typical immunological reactions in patients with terminal stage CKD depending on the duration of treatment after allogeneic kidney transplantation with establishing key parameters and formulas of immunocorrection targets.

5. To study the effectiveness of the use of ozone solutions in the comprehensive treatment of patients with terminal stage CKD on program hemodialysis.

6. To develop a computer program for optimizing standard immunosuppressive therapy in patients with terminal stage CKD after allogeneic kidney transplantation.

SCIENTIFIC NOVELTY:

Typical immunological disorders in patients with terminal stage CKD depending on the duration of replacement therapy and blood genetic markers have been established.

Typical immunological disorders in kidney transplant recipients depending on blood genetic markers at various time points after transplantation have been documented.

Key indicators of immunological disturbances and the formula of immune system disorders in patients receiving treatment on hemodialysis have been determined.

Key indicators of immunological disturbances and formulas of immunocorrection targets in patients after the combination of traditional treatment with ozone therapy have been identified.

Key indicators of immunological disturbances and formulas of immunocorrection targets in patients after kidney transplantation have been established.

A computer program for optimizing standard immunosuppressive therapy in patients after kidney transplantation has been developed (rationale proposal No. 2710 dated 25.11.2004; certificate of official registration of a computer program No. 2005611432 dated 15.06.2005).

PRACTICAL SIGNIFICANCE:

Typical immunological disorders in patients with terminal stage CKD depending on the duration of hemodialysis treatment and blood genetic markers have been studied.

Formulas of immune system disorders have been determined that justify the choice of an immunocorrective agent in the complex therapy of patients receiving treatment on hemodialysis.

A formula of immunocorrection targets has been identified that justifies the inclusion of ozone therapy in the complex therapy of patients with terminal stage CKD.

Formulas of immunocorrection targets have been determined that justify the choice of an immunocorrective agent in the complex therapy of patients after kidney transplantation.

A computer program for optimizing standard immunosuppressive therapy in patients after kidney transplantation has been developed.

IMPLEMENTATION OF RESULTS AND APPROVAL.

Dissertation materials are used in the educational process at the departments of hospital surgery, microbiology, virology, and immunology of the Voronezh State Medical Academy named after N.N. Burdenko. The results of the work have been implemented in clinical practice at the Voronezh Interterritorial Transplantation Center based on the urological kidney transplant department of Voronezh Regional Clinical Hospital No. 1. Fifteen printed works on the dissertation topic have been published, including five in central and international press, and one methodological manual recommended by the Methodological Association for Medical and Pharmaceutical Education of Russian universities as a textbook for medical university students. A certificate of official registration of a computer program and a certificate of rationalization proposal have been obtained.

The main provisions of the dissertation were presented at the jubilee scientific-practical conference dedicated to the 85th anniversary of the Voronezh State Medical Academy named after N.N. Burdenko "Prevention and Treatment of Diseases in Modern Environmental and Hygienic Conditions" Voronezh, 2003; an interregional conference of young scientists "New Technologies in Biology and Medicine" Voronezh, 2004; the All-Russian scientific-practical conference "Kidney Diseases: Epidemiology, Diagnosis, Treatment" Kyzyl, 2004; the Jubilee scientific conference of the Kursk State Medical University and a session of the Central Black Earth Scientific Center of the Russian Academy of Medical Sciences dedicated to the 70th anniversary of the Kursk State Medical University Kursk, 2005; the All-Russian scientific-practical conference "Clinical Organ Transplantation" Moscow, 2005; an interregional scientific-practical conference of young scientists with international participation "Modern Directions of Theoretical and Practical Medicine" Voronezh, 2005; the international scientific-practical conference "Actual Issues of Emergency Surgery" Ukraine, Kharkov, 2005.

VOLUME AND STRUCTURE OF THE DISSERTATION. The dissertation is presented on 140 pages of typed text and consists of an introduction, 4 chapters, and a conclusion. The first chapter considers the history and current state of the question. The second chapter is dedicated to the characteristics of research objects and the description of technical provision, materials, and clinical research methods.