Features of the Clinical Course and Renal Hemodynamics in Children with Chronic Pyelonephritis Developing Against the Background of Connective Tissue Dysplasia

The dissertation is devoted to the study of features of the clinical course and hemodynamics of the kidneys in children with chronic pyelonephritis developing against the background of connective tissue dysplasia. The investigation was conducted at Rostov State Medical University and validated in nephrological centers in Chelyabinsk. A comprehensive clinical-instrumental examination using ultrasonic Dopplerography of renal vessels was carried out. It has been demonstrated that at varying degrees of severity of connective tissue dysplasia, the development of obstructive forms of pyelonephritis against the background of anomalies of renal position, often combined with dismetabolic disturbances and the development of tubular insufficiency, is typical. For the first time, it has been established that in the pathogenesis of chronic pyelonephritis against the background of connective tissue dysplasia, vessels of varying calibers — from trunk renal arteries to interlobar arteries — are involved, which is reflected in the ultrasonic velocity parameters of hemodynamics and indices of peripheral resistance of renal vessels.

Relevance of the Problem

Chronic pyelonephritis is the most common infectious kidney disease in children (M.S. Ignatova, 2001; G.A. Makovetskaya et al., 2003; S. Sreenorsimmp, S. Hellerstein, 1998; W.R. Cottell, 1999). M.V. Ermann (1996) includes the diagnosis of pyelonephritis among the 19 most prevalent diagnoses of urinary system pathology registered in children. The diversity of clinical forms of urinary tract infection in children is determined by the level of involvement of the urinary system organs, conditions of infection, presence or absence of organic or functional obstruction of the urinary tract, and impairment of hemodynamics (A.V. Papayan, N.D. Savenkova, 1997; I.N. Zakharova, 2001; V.I. Kirillov et al., 2004; K.A. Burbidge, 1984; J.C. Mulier, 1994).

Many authors believe that most severe kidney diseases are a consequence of timely unrecognized diseases and developmental defects of the urinary system in children, accompanied by a slowly progressive decline in tubular kidney functions (N.A. Korovina, I.N. Zakharova, N.P. Gerasimova, O.V. Savelieva, 2004; I. Gordon, 1990; M. Nuutinen, 1999; J.C. Madoni, 2001).

Chronic pyelonephritis in recent times has acquired a paucisymptomatic and latent disease course, which complicates timely diagnosis and, consequently, delays the onset of adequate therapeutic, rehabilitative, and preventive measures (A.A. Vyalkova, 1989; N.A. Korovina, 1993; L.I. Antonova, 1996; E. Bourdon, 2001).

Much work has been devoted to the study of the pathogenesis of chronic pyelonephritis. It is well known that in the development of chronic pyelonephritis, a certain significance is attached to the states of organism resistance, agent virulence, the presence of foci of infection, the degree of impairment of urine passage, and the magnitude of microbial invasion (N.A. Lopatkin, A.G. Pugachev, 1986; O.V. Bukharin, 1997; I.A. Borisov, 2000; N.A. Korovina, I.N. Zakharova, 2002; P.L. Ogra, H.S. Faden, 1985; A. Mayrire, 1990; M.R. Andrich, 1992; R.D. Berg, 1994).

There are numerous indications of the influence of organic and functional obstruction in the process of formation of chronic pyelonephritis (I.Yu. Balalaeva, 1999; A.V. Papayan, 2001; C.J. Zusman, 1998). As a result of obstruction of the urinary tract, damage to kidney tissue occurs due to the development of aseptic immune reactions or bacterial inflammation with subsequent development of nephrosclerosis, the degree of which determines the volume of kidney parenchyma excluded from functioning (K.B. Roberts, 1983, R.L. Chevalier, et al., 1994, 1998, 1999, 2000).

Obstruction may be caused by various developmental anomalies of the kidneys and urinary tract (N.A. Lopatkin, 1986; A.V. Papayan, I.D. Savenkova, 1997; A.Sh. Rumyantsev, et al., 2000; T.V. Sergeeva, O.V. Komarova, 2002; N.A. Korovina, I.N. Zakharova, et al., 2003).

In recent years, the formation of urinary tract infection, including pyelonephritis, has been associated, in addition, with the presence of various systemic defects in the child's organism. In particular, significance is attributed in the genesis of chronic pyelonephritis to connective tissue dysplasia, which manifests as a violation of the supportive connective tissue framework during the embryonic and postnatal periods due to altered fibrillogenesis of the extracellular matrix, which can lead to a disturbance of homeostasis — at the tissue, organ, and organism levels — in the form of various defects of visceral and locomotor organs with a progressive course (O.V. Lisichenko, G.N. Vereshagina et al., 1993; V.A. Artamonova, Yu.N. Zakharova et al., 1999; V.F. Demin et al., 2005; M.J. Glesby, 1989; A. Mayrire, 1990).

The development of pyelonephritis in the context of connective tissue dysplasia may be facilitated by the presence of vascular wall changes, since this pathology reveals features of the functional state of medium- and small-caliber vessels, due to aneurysms of renal vessels (V.M. Yakovlev, 1993; V.M. Yakovlev, G.I. Nechaeva, 1994).

Doppler assessment of renal hemodynamics plays an important role in evaluating the functional state of the kidneys, the change in whose characteristics makes it possible to detect impairment of intrarenal blood flow in inflammatory kidney diseases in children (M.I. Pykov, Yu.M. Skokov, N.A. Korovina, 1999; Yu.B. Perevezentseva, N.N. Smirnova, 2003; M.V. Averchenko, E.E. Klimova, I.G. Fedotov, 2005; U. Beseghi, 1996; G. Nilson, Loren, N. Person, 1998; A.F. Abdalah et al., 1999).

Questions regarding the features of the clinical course of chronic pyelonephritis in children with connective tissue dysplasia, the role of changes in renal blood flow impairment, and changes in vascular resistance in renal arteries in the formation of this disease against the background of connective tissue dysplasia are practically not addressed in the literature.

In connection with this, the present investigation has been undertaken.

Objective of the investigation: Based on the conduct of a comprehensive clinical-instrumental examination using ultrasonic Dopplerography of renal vessels, to identify the features of the clinical course and hemodynamics of the kidneys in children with chronic pyelonephritis developing against the background of connective tissue dysplasia.

Tasks of the investigation:

1. To determine the features of the clinical course of chronic pyelonephritis in children developing against the background of connective tissue dysplasia.

2. To determine the features of renal hemodynamics in children with non-obstructive forms of chronic pyelonephritis in the inactive phase of the disease.

3. To identify the features of renal hemodynamics in children with chronic pyelonephritis developing against the background of connective tissue dysplasia.

4. To determine the features of hemodynamic disturbances in the kidneys in chronic pyelonephritis in children with varying degrees of severity of connective tissue dysplasia.

5. To evaluate the significance of using impulse Dopplerography as a method necessary for the comprehensive examination of children in order to more early detection of hemodynamic disturbances of the kidneys in children with pyelonephritis developing against the background of connective tissue dysplasia.

Scientific Novelty

As a result of the conducted work, the clinical features of chronic pyelonephritis forming against the background of systemic connective tissue dysplasia have been identified. It has been proven that at varying degrees of severity of connective tissue dysplasia, the development of obstructive forms of pyelonephritis against the background of anomalies of renal position, often combined with dismetabolic disturbances and the development of tubular insufficiency of kidney function, is typical. For the first time, it has been established that in the process of formation of chronic pyelonephritis in the context of connective tissue dysplasia, vessels of varying calibers are involved — large (trunk renal arteries), medium (segmental renal arteries), and interlobar renal arteries. This is evidenced by changes in the ultrasonic velocity parameters of hemodynamics and indices characterizing peripheral resistance of renal vessels.

Practical Significance

The results of the conducted work consist in the identification of hemodynamic disturbances in the kidneys in children with chronic pyelonephritis against the background of connective tissue dysplasia.

In this case, not only segmental renal arteries but also trunk renal arteries are involved in the pathological process, which should be confirmed by ultrasonic investigation of renal hemodynamics.

Taking into account the results of Dopplerography, in particular, changes in velocity parameters (maximum systolic blood flow velocity, minimum diastolic blood flow velocity, time-averaged blood flow velocity) and indices characterizing peripheral resistance of renal vessels, during dispensary observation by nephrologists of children with signs of connective tissue dysplasia may contribute to more early detection of signs of tubular insufficiency of the kidneys.

Principal Propositions of the Dissertation to be Defended

1. In chronic pyelonephritis developing in children with varying degrees of expression of connective tissue dysplasia by phenotypic signs and in the presence of instability of the cervical vertebrae of the antelisthesis or retrolisthesis type, the development of obstructive forms of the disease against the background of anomalies of renal position in combination with dismetabolic disturbances and the development of tubular insufficiency is more typical.

2. In the formation of chronic pyelonephritis in children, disturbances of renal hemodynamics are observed, as evidenced by the changes detected by impulse Dopplerography in such velocity parameters as maximum systolic velocity, terminal diastolic velocity, as well as time-averaged blood flow velocity and indices reflecting peripheral resistance in the renal vessels. The character of changes in renal hemodynamics depends on the presence of connective tissue dysplasia in children.

3. Changes in renal hemodynamics in chronic pyelonephritis in children against the background of connective tissue dysplasia are characterized by a decrease in velocity parameters and indices reflecting peripheral resistance at the level of renal and segmental arteries, as well as a decrease in maximum systolic velocity at the level of small-caliber arteries.

Implementation of Research Results in Practice

The results obtained during the comprehensive investigation in children with chronic pyelonephritis developing against the background of connective tissue dysplasia have been implemented in the work of the nephrological center of MUZ DGB No. 1 and the nephrological department of MUZ DGKB No. 7 in the city of Chelyabinsk.

The results of the dissertation work are used in the educational process with students, as well as clinical residents and interns at the Department of Pediatric Diseases No. 3 of Chelyabinsk State Medical Academy.

Validation of the Work

The principal propositions of the dissertation work were presented at a scientific-practical conference dedicated to the 50th anniversary of GUZ DDKB on Station Chelyabinsk of GOUZhD (Chelyabinsk, 2003), a regional conference "Health of Adolescents: Problems and Ways of Their Solution" (Vladivostok, 2004), a scientific session dedicated to the 60th anniversary of the Chelyabinsk State Medical Academy "Actual Problems of Medical Science and Practical Healthcare" (Chelyabinsk, 2004), a conference dedicated to the 25th anniversary of the Ural State Academy of Postgraduate Education "Actual Problems of Medical Science, Technologies, and Professional Education" (Chelyabinsk, 2005), the I Russian Congress "Modern Technologies in Pediatrics and Pediatric Surgery" (Moscow, 2005).

Publications

Five scientific works have been published on the material of the dissertation.

Structure and Volume of the Dissertation

The dissertation is presented on 157 pages of typed text and consists of an introduction, a review of literature, 4 chapters of original research, a conclusion, propositions, and a reference list including 159 domestic and 78 foreign sources. The work is illustrated by 28 tables, 9 figures, and 9 diagrams.