Clinicofunctional Assessment of the Urinary System State and Determination of Treatment Tactics in Children with Vesicoureteral Reflux

The dissertation is devoted to the clinicofunctional assessment of the state of the urinary system in children with vesicoureteral reflux (VUR) and the development of a differentiated tactics for the management and treatment of this patient contingent. In the work, the features of clinical manifestations and the functional state of the urinary tract have been studied; disturbances of urodynamics of the lower urinary tract of varying degrees of severity, always accompanying VUR, have been identified. The oxidant and antioxidant status of children with this disease has been investigated, and a connection between the degree of urodynamic disturbances and the state of antioxidant protection has been established. On the basis of the obtained data, a differentiated algorithm for diagnosis and complex treatment of children with VUR has been developed, taking into account the initial functional state of urodynamics and the antioxidant status, which has made it possible to increase the efficacy of conservative therapy and reduce the number of surgical interventions.

RELEVANCE,

One of the most pertinent issues in pediatric urology remains the problem of vesicoureteral reflux. Over recent years, there has been a sharp increase in interest among urologists and pediatric surgeons in this disease, as it is one of the leading causes leading to the development of pyelonephritis and chronic renal insufficiency. According to data from various authors, vesicoureteral reflux is encountered in 10–53% of cases among patients with urinary tract infections (5, 35, 9).

Over the past decade, significant advances have been achieved in endourology and pharmacology of the urinary tract, which have found their reflection in the treatment of children with VUR. The proportion of open surgical interventions has significantly decreased, and the role of conservative therapy has increased. At the same time, the very nature of the disease and the complexity of conducting well-grounded pathogenetic treatment (identifying factors of substantial significance in the development of VUR in a particular child) compel the search for ways to increase the efficacy of conservative therapy and the justified application of minimally invasive and surgical interventions. It is known that for the formation of a condition in which urine refluxes into the kidney, two components must be present: anatomical insufficiency of the ureterovesical junction and functional disturbances of the urinary bladder exerting a prolonged influence on the urodynamics of the upper and lower urinary tracts. At the present time, the significance of various neuromuscular dystrophies and the tissue form of myelodystrophy as the most serious factors largely determining the course of the disease and the prognosis, and often leading the patient to disability or chronic renal insufficiency, is not disputed. The tissue form of myelodystrophy manifests not only in urodynamic disturbances of the lower urinary tract (levator-sphincter imbalance, neurogenic bladder dysfunction) but also in tissue disturbances in the walls of the urinary bladder and ureter, being a continuously acting factor, it determines ineffective therapy in patients with VUR. Identification of this pathology requires a clear diagnostic algorithm for determining indications for the appointment of therapy directed not only at restoring normal passage of urine through the ureter but also at correcting bioenergetic disturbances occurring directly in the urinary bladder itself. This implies a change in the principles of conservative therapy and determines the treatment tactics of the patient in the presence of VUR, affecting the most substantial pathogenetic links of the disease that are of importance for the prognosis in each specific case of VUR in children.

At the present stage, the role and significance of mitochondrial pathology in children with dysfunctions is being discussed (8). A change in the antioxidant and oxidant activity of blood has been identified in patients with chronic pyelonephritis and chronic renal insufficiency (23, 145). Although these conditions are present in VUR and in a considerable proportion of cases, at the present time there are no specific recommendations for the elimination of mitochondrial insufficiency in children and its consequences in the form of activation of lipid peroxidation, and accordingly, the final treatment tactics has not been determined.

RESEARCH OBJECTIVE: On the basis of studying the features of clinical manifestations and the functional state of the urinary tract in children with vesicoureteral reflux, to develop a differentiated tactics for the management and treatment of such patients and to evaluate the results of the latter.

RESEARCH TASKS.

1. To evaluate the oxidant and antioxidant status in children with vesicoureteral reflux by means of investigation of antioxidant activity of blood and products of lipid peroxidation.

2. To determine the clinicofunctional criteria for disturbance of urodynamics of the lower urinary tract in vesicoureteral reflux.

3. To develop a differentiated treatment tactics for children with reflux depending on the degree of urodynamic disturbance, taking into account the state of the antioxidant status.

4. To evaluate the results of differentiated treatment of children with vesicoureteral reflux.

SCIENTIFIC NOVELTY.

For the first time, changes in the oxidant and antioxidant status in children with VUR have been identified and studied. A connection between disturbances of urodynamics of the lower urinary tract and the degree of disturbances of antioxidant protection has been noted.

The features of the clinical course and the diagnostic algorithm for the management of patients with VUR have been determined. A differentiated approach to complex treatment of children with VUR has been developed, taking into account the initial functional state of urodynamics of the lower urinary tract.

It has been established that vesicoureteral reflux is always accompanied by disturbances of urodynamics of the lower urinary tract of varying degrees of severity.

The necessity of conducting a course of mitochondrial therapy prior to correction of urodynamic disturbances has been noted, as it changes the type and degree of urodynamic disturbance.

Complex therapy of children with VUR, taking into account the antioxidant link of pathogenesis, has been substantiated.

PRACTICAL SIGNIFICANCE.

A new method of intraurodynamic examination of children has been introduced and refined, increasing the percentage of detection of VUR and improving the quality of diagnosis of dysfunctions of the lower urinary tract.

Investigation of urodynamics of the lower urinary tract in children with VUR has made it possible to conclude the necessity of predominantly invasive methods of examination.

The identified reliable differences of the antioxidant status from normal values and its increase upon oxidant therapy allow the assertion that disturbances of cellular bioenergetics of the detrusor play an important role in the pathogenesis of VUR.

Analysis of the obtained data and application of the proposed algorithm for diagnosis of urodynamic disorders with investigation of the antioxidant status in VUR have demonstrated high efficacy of the use of a complex of pharmacotherapy and physiotherapy in children with vesicoureteral reflux.

The use of the algorithm of differentiated treatment tactics in VUR has made it possible to reduce the number of surgical interventions and associated postoperative complications.

PRESENTATION AND DISCUSSION.

The main provisions of the dissertation were reported and discussed at the regional physician-scientific-practical conference dedicated to the 50th anniversary of the establishment of MUZ "Children's Regional Hospital" of the Jewish Autonomous Oblast (Birobidzhan, 2003); the Pacific Scientific-Practical Conference of students and young scientists with international participation (Vladivostok, 2004); the scientific-practical conference of MUZ DKGKB (Vladivostok, 2004); the 1st Regional Scientific-Practical Conference "Achievements and Prospects of Development of Pediatric Surgery" (Vladivostok, 2005); the scientific-practical conference "Endoscopy and Endoscopic Surgery of Children and Adolescents" (Khabarovsk, 2005); the session of the problem commission of GOU VPO VGMU Roszdrav "Motherhood and Childhood" (Vladivostok, 2005).

IMPLEMENTATION INTO PRACTICE AND PUBLICATIONS.

The results of the investigation have been applied in the work of the Primorsky Krai Uro-Nephrological Center based on the departments of urology and nephrology of MUZ "Children's City Clinical Hospital" of Vladivostok. The obtained data are used in the educational process at the Department of Pediatric Surgical Diseases and the course of urology of GOU VPO VGMU Roszdrav. A certificate of a rationalization proposal No. 2580 dated 18.06.04 has been received (Golovina O. B., Shapkina V.V., Danilov V.V.). Based on the materials of the dissertation, 13 printed works have been published in the press and central press.

MAIN PROPOSITIONS SUBMITTED FOR DEFENSE.

1. The degree of urodynamic disturbances in children with vesicoureteral reflux is associated with a change in the state of the oxidant and antioxidant link. Investigation of the antioxidant status and pharmacological correction of it make possible the step-by-step treatment of urodynamic disturbances of the lower urinary tract.

2. Complex treatment of children with vesicoureteral reflux, directed, inter alia, at correction of the antioxidant status, increases the efficacy of traditional methods of treatment, allows a reduction in the number of exacerbations and an increase in the duration of remission of pyelonephritis and urinary tract infection, as well as, within a shorter period, a reduction in the degree of reflux or acceleration of its remission.

STRUCTURE AND VOLUME OF THE DISSERTATION.

The dissertation is presented on 158 pages of typed text and consists of an introduction, a literature review, 5 independent investigations, a conclusion, conclusions, practical recommendations, a list of references including 220 sources, of which 70 domestic and 50 foreign. The text is illustrated by 28 figures, 26 tables, and 9 appendices.