Pyelonephritis in children

Pyelonephritis in children is a special case of urinary tract infection (UTI). A common feature of all UTIs is the growth and multiplication of bacteria in the urinary tract.

Urinary tract infections are the second most common after an infectious pathology of the respiratory tract. About 20% of women carry them in their lives at least once. The disease quite often recurs (more than 50% of cases in girls and about 30% in boys). There are UTIs with lesions:

• lower urinary tract - cystitis, urethritis;
• upper - pyelonephritis.

Pyelonephritis is a nonspecific acute or chronic microbial inflammation of the epithelium of the bowel-and-pelvis system and interstitial kidneys with secondary involvement of tubules, blood and lymph vessels in the process.

Pyelonephritis in children is the most serious type of UTI, it requires timely diagnosis and adequate treatment, because when involved in the inflammatory process of interstitial kidneys, there is a risk of their sclerosis and development of menacing complications (kidney failure, arterial hypertension).

The true share of pyelonephritis in children in the structure of all UTIs is difficult to determine, as almost a quarter of patients can not accurately determine the localization of the inflammatory process. Pyelonephritis, as well as UTI as a whole, occurs in any age groups: in the first 3 months of life they are more often sick with boys, and at an older age it is approximately 6 times more likely to be met in women. This is due to the peculiarities of the structure of the female genitourinary system, allowing easy colonization of the urethra by microorganisms and an upward spread of infection: the proximity of the outer orifice of the urethra to the anus and vagina, its small length and relatively large diameter, a peculiar rotational movement of urine in it.

For the incidence of pyelonephritis, three age peaks are characteristic:

• early childhood (about 3 years) - prevalence of UTI reaches 12%;
• young age (18-30 years) - mostly women suffer, often the disease occurs during pregnancy;
• elderly and senile age (over 70 years) - the incidence in men is growing, which is associated with a greater prevalence of prostatic disease, as well as an increased incidence of chronic diseases - risk factors (diabetes, gout).

Pyelonephritis, which occurred in early childhood, often turns into a chronic form, worsening during puberty, at the beginning of sexual activity, during pregnancy or after childbirth.

[1], [2], [3], [4]

Causes of pyelonephritis in children

Pyelonephritis in children is a nonspecific infectious disease, i.e. For him, there is no specific causative agent. In most cases, it is caused by gram-negative bacteria; usually in the urine reveal any one species (the presence of several more often indicates a violation of the technique of urine sampling).

Escherichia coli (the so-called uropathogenic strains - 01, 02, 04, 06, 075) - in 50-90% of cases.

Another intestinal microflora (Proteus, Pseudomonas aeruginosa, Klebsiella, Citrobacter, Senatia, Acinetobacter) is less common. Among the strains of the protein, the most pathogenic are P. Mirabilis, P. Vulgaris, P. Rettegri, P. Morganii (they are detected in approximately 8% of children suffering from pyelonephritis). About the same frequency, Enterococcus and K. Pneumoniae are detected, and Enterobacter and S. Aeruginosa in 5-6% of cases (this causative agent causes persistently current forms of pyelonephritis, it is often detected in the urine of persons who have undergone surgery on the organs of the urinary system ). Enterobacter cloacae, Citrobacter, Serratia marcescens are typical pathogens of nosocomial forms of the disease. Gram-positive bacteria - Staphylococcus epidermidis and aureus, Enterococcus - are found only in 3-4% of patients with PN. Considering the above, with the empirical appointment of treatment proceed from the assumption that pyelonephritis is caused by gram-negative bacteria.

Pyelonephritis of a fungal etiology (for example, caused by Candida albicans) is very rare and mostly in people with immunodeficiency states. Non-polycillic pyelonephritis predominantly occurs in children with gross anatomical abnormalities of the urinary system or after urological operations, catheterization of the bladder or ureters. For such cases, there is the term "complicated", or "problem" IMT. Thus, the leading role in the development of the disease belongs to autoinfection with a predominance of intestinal microflora, less often - pyogenic cocco from nearby or distant inflammatory foci.

Despite the wide spectrum of microorganisms that can participate in the development of the inflammatory process in the kidneys, the mechanism of the effect of bacteria on the organs of the urinary system is most studied in relation to E. Coli. Its pathogenicity is mainly associated with K- and O-antigens, as well as with P-fimbriae.

• K-antigen (capsular) due to the presence of an anionic group prevents effective phagocytosis, has low immunogenicity and is therefore poorly recognized by the protective system (these factors contribute to the long-term existence of bacteria in the body).
• O-antigen is part of the cell wall, has the properties of endotoxin and promotes the adhesion of the microorganism.
• P-fimbriae are the thinnest mobile filaments with special molecules-adhesins. With their help, bacteria bind to glycolipid receptors of epithelial cells, which allows them to penetrate into the upper urinary tract even without vesical-reflux reflux (for example, E. Coli with
• P-fimbriae is found in 94% of patients with proven pyelonephritis and only 19% with cystitis).

In addition, the virulence of the microorganism determines non-fimbrial adhesion factors (facilitate the ascending path of bacteria penetration), hemolysin (causes hemolysis of erythrocytes, promotes the growth of a bacterial colony), flagella (ensure the mobility of bacteria, play a large role in the development of hospital urinary infection, particularly associated with catheterization bladder) and bacterial glycocalyx.

A study of the relationship between E. Coli pathogenicity factors and the course of UTI in children has shown that bacteria with several pathogenicity factors are detected in pyelonephritis in children much more often (in 88% of cases) than in cystitis and asymptomatic bacteriuria (in 60 and 55%, respectively). Acute pyelonephritis causes various strains of Escherichia coli, and chronic relapsing - mainly serogroups O and 02.

For bacteria that can survive in the human body for a long time, the following properties are characteristic:

• antilizimic activity - the ability to inactivate lysozyme (found in all species of enterobacteria and Escherichia coli, as well as in 78.5% of proteic strains);
• anti-interferon activity - the ability to inactivate bactericidal leukocyte interferons;
• anticomplementary activity - the ability to inactivate complement.

In addition, a number of microorganisms produce beta-lactamases, which destroy many antibiotics (especially penicillins, cephalosporins I and II generations).

When investigating the pathogenicity of microorganisms isolated under various forms of UTI, it was found that in children with transient bacteriuria, bacteria are low in the urine, and with highly virulent bacteria.

[5], [6], [7], [8]

How does the child develop pyelonephritis?

Primary ways of infection into the kidney:

• hematogenous - is observed in rare cases (more often - in newborns with sepsis caused by Staphylococcus aureus, less often - at an older age in the background of systemic infections with bacteremia), embolic jade (apo-stems or kidney carbuncle) may develop, when circulating microorganisms linger in the glomeruli and lead to the appearance of abscesses in the cortical substance;
• ascending - basic.

Normally, the urinary tract is sterile, with the exception of the distal urethra. Colonization of the mucous membrane of the lower urinary tract is impeded by a number of factors:

• hydrodynamic protection (regular and complete emptying of the bladder) - mechanical removal of bacteria;
• glycoproteins, which prevent bacteria from attaching to the mucosa (uromucoid reacting with E. Coli fimbriae);
• humoral and cellular immunity (IgA, IgG, neutrophils and macrophages);
• low pH of urine and fluctuations in its osmolarity.

In boys during puberty, the secret of the prostate gland, possessing bacteriostatic properties, also plays a protective role.

Transient disturbance of local protective factors can be a consequence of microcirculation defects in the wall of the bladder during hypothermia or after the acute respiratory viral infection. With neurogenic bladder dysfunction, the accumulation of residual urine disrupts the hydrodynamic defense and promotes the attachment of bacteria to the mucous membrane of it and the ureters.

Sources of bacteria that enter the urinary tract are the colon, vagina, or cavity of the foreskin, so the risk of pyelonephritis in children increases with intestinal dysbacteriosis and inflammatory diseases of the vulva. Treatment with antibiotics (for example, with an infection of the respiratory tract) can lead not only to intestinal dysbiosis, but also to changes in the composition of the vaginal microflora or the foreskin: to suppress saprophytic strains and the appearance of uropathogenic bacteria. Constipation also predisposes to disruption of the intestinal biocenosis in the child.

An important role in the development of pyelonephritis in children is played by:

• the initially existing obstacle to the outflow of urine - mechanical (congenital - hydronephrosis, urethral valve, acquired - urolithiasis or dizmetabolic nephropathy with crystalluria, resulting in micro-obstruction at the level of the tubules even without stone formation) or functional (neurogenic bladder dysfunction);
• vesical-pulmonary reflux (PLR) - retrograde transfer of urine into the upper urinary tract due to failure of the vesicoureterial anastomosis.

Thus, the risk factors for the development of pyelonephritis in children include anatomical abnormalities of the urinary system, PLR, metabolic disorders (mainly persistent oxalate or urate crystalluria), urolithiasis, and bladder dysfunction.

However, for the development of the microbial inflammatory process in the kidney, in addition to these factors, the state of the body's immune system is important. It is established that the emergence of infections of the urinary system is facilitated by a deficiency of secretory IgA, as well as changes in the pH of the vagina, broken hormonal profile, recent infections and intoxications. In children who have had UTIs during the newborn period, often associated pus-inflammatory diseases, intestinal dysbacteriosis, hypoxic encephalopathy, signs of morphofunctional immaturity. For children who have fallen ill with pyelonephritis at the age of 1 month to 3 years, frequent ARVI, rickets, atopic dermatitis, IDA, intestinal dysbacteriosis are typical.

In the development of pyelonephritis in the ascending pathway of penetration of the pathogen, several stages are distinguished. First, infection of the distal urethra occurs. Later, the infection spreads to the bladder, from which bacteria enter the pelvis and kidney tissue (largely due to PLR) and colonize them. Penetrating into the renal parenchyma, microorganisms cause inflammation (it largely depends on the characteristics of the body's immune system). In this process, we can distinguish the following points:

• production of macrolephages and monocytes of interleukin-1, which forms an acute phase response;
• liberation by phagocytes of lysosomal enzymes and superoxide damaging the tissue of the kidneys (primarily the most structurally and functionally complex cells of the tubular epithelium);
• synthesis of specific antibodies in lymphocytic infiltrates;
• the production of serum immunoglobulins against O- and K-antigens of bacteria;
• sensitization of lymphocytes to bacterial antigens with an increase in the proliferative response to them.

The consequence of the above processes is an inflammatory reaction (for the initial stages, neutrophil infiltration with a different degree of exudative component is characteristic, and for the subsequent stages, the predominance of lymphohystocytes is characteristic). In the experiment it was shown that in the first hours after the entry of bacteria into the kidney, processes similar to those in the shock lung: activation of complement components, which leads to aggregation of platelets and granulocytes; cytolytic damage to tissues (direct and mediated by inflammatory mediators). The described processes lead to ischemic necrosis of the kidney tissue in the first 48 hours of the disease. Damaged tissue is easily infected with bacteria, and ultimately, microabscesses occur. Without adequate treatment, the renal blood flow decreases and the volume of the functioning parenchyma decreases. In the chronic course of the process, as it progresses, the synthesis of the "counter" antibodies and the formation of specific T-killers sensitized to the renal tissue are noted. Eventually, the progressive death of nephrons can lead to interstitial sclerosis and the development of chronic renal failure (CRF).

Pathological anatomy

Acute pyelonephritis in children can occur in the form of purulent or serous inflammation.

Purulent inflammation. Bacteria (most often staphylococcus), having penetrated into the kidney, find favorable conditions for reproduction in hypoxia zones. The products of their vital activity damage the vascular endothelium, thrombus formation occurs, and infected thrombi in the vessels of the cortex cause infarcts with subsequent suppuration. Education possible:

• multiple small foci - apostematous (pustular) nephritis;
• large abscesses in any part of the cortex - carbuncle of the kidney;
• perinephalic abscess - paranephritis. 

Serous inflammation (most cases of pyelonephritis) - edema and leukocyte infiltration of interstitium. In the edematous areas and in the lumen of the tubules, multinucleate cells are detected. The glomeruli are usually unchanged. Inflammation captures the kidney unevenly, and affected areas can coexist with normal tissue. The zones of infiltration are located mainly around the collecting tubes, although sometimes they are found in the cortical layer. The process ends with scarring, which makes it possible to talk about the irreversibility of changes even with acute pyelonephritis.

Chronic pyelonephritis in children. The changes are mainly unevenly expressed mononuclear cell infiltration and focal sclerosis of the parenchyma. During exacerbation, exudates containing polynuclear cells are found in the interstitium. End the process atrophy of the tubules and replace them with connective tissue. In chronic pyelonephritis, the glomeruli also suffer (the main cause of their ischemia and death is vascular damage during inflammation in the interstitium).

With the progression of pyelonephritis, interstitial sclerosis is formed, i.e. Proliferation of connective tissue in the interstitium, which also leads to scarring of glomeruli and a progressive decrease in kidney function. One of the main signs of pyelonephritis, which distinguishes it from other tubulointerstitial lesions, is changes in the epithelium of calyx and pelvis: signs of acute (edema, microcirculation disturbance, neutrophilic infiltration) or chronic inflammation (lymphohistiocytic infiltration, sclerosis).

Symptoms of pyelonephritis in children

Since pyelonephritis in children is an infectious disease, it has the following symptoms:

• general infectious - raising the body temperature to 38 ° C, chills, intoxication (headache, vomiting, lack of appetite), pain in the muscles and joints is possible;
• local - frequent painful urination when the infection spreads upward (when the mucous membrane of the bladder is involved in the inflammatory process), abdominal pain, in the side and in the waist (they are caused by the extension of the kidney capsule in the edema of the parenchyma).

In the first year of life, the clinical picture is dominated by general infectious symptoms. In infants, patients with PN, often noted regurgitation and vomiting, loss of appetite, stool disorder, pale gray skin; with high fever, there may be signs of neurotoxicosis and meningeal symptoms. Older children in two-thirds of cases complain of abdominal pain, usually in the near-buccal region (irradiation from the diseased organ into the solar plexus region). The pain can give up the ureter in the thigh and groin. Pain syndrome is usually mild or moderate, its increase is noted when involving in the inflammatory process of pericardial cellulose (with relatively rare staphylococcal PN) or in violation of the outflow of urine.

Exacerbation of chronic pyelonephritis in children sometimes occurs with scant symptoms. In the latter case, only a purposeful collection of anamnesis allows to identify complaints of unsharp pains in the lumbar region, episodes of "unmotivated" subfebrile condition, implicit urination disorders (imperative urges, occasionally enuresis). Often the only complaints are manifestations of infectious asthenia - pallor of the skin, increased fatigue, decreased appetite, in young children - weight loss and stunting.

For pyelonephritis edematous syndrome is not typical. On the contrary, at times of exacerbation, there are signs of exsicosis, both as a result of fluid loss due to fever and vomiting, and at the expense of a decrease in the concentration function of the kidneys and polyuria. Nevertheless, sometimes light easiness of the eyelids is noticeable in the mornings (it arises from disturbances in the regulation of the water-electrolyte balance).

Arterial pressure in acute pyelonephritis does not change (in contrast to the debut of acute glomerulonephritis, often occurring with its increase). Arterial hypertension (AH) is a companion and complication of primarily chronic PN in cases of development of nephrosclerosis and progressive decrease in organ function (in such cases, hypertension is often persistent and can acquire a malignant character).

In general, the symptoms of pyelonephritis in children are low-specific, and a crucial role in its diagnosis is played by laboratory symptoms, especially changes in the general analysis of urine and the results of bacteriological research.

Classification of pyelonephritis in children

There is no single, universally used PN classification. According to the 1980 classification of the Russian pediatrics, the following forms of pyelonephritis are distinguished:

• primary;
• secondary - develops against the background of the existing pathology of the urinary system (congenital anomalies, neurogenic bladder dysfunction, PLR), with metabolic disorders with the formation of crystals or concrements in the urine (oxaluria, uraturia, etc.), as well as with congenital immunodeficiency states, diseases endocrine system. Foreign researchers identify obstructive and non-obstructive pyelonephritis in children.

In the course of the process, one distinguishes:

• acute pyelonephritis in children;
• chronic pyelonephritis in children - prolonged (longer than 6 months) or recurrent disease.

Moreover, in chronic PN exacerbation causes the same strain of bacteria, and if another is detected, the disease is regarded as a repeated episode of acute PN.

The phases of pyelonephritis:

• at acute PN - heat, stagnation and remission;
• with chronic PN - exacerbation, incomplete (clinical) remission (there are no clinical and laboratory signs of inflammation activity, but there are changes in urinalysis) and complete (clinical and laboratory) remission (there are no changes in urine tests).

The classification of any kidney disease contains a characteristic of their functional state. In acute PN or with exacerbation of chronic kidney function can be preserved, sometimes note its partial disorders (primarily changes in concentration ability), it is also possible to develop acute or chronic renal failure.

Classification of pyelonephritis (Studenikin M.Ya., 1980, supplemented by Maidannik VG, 2002)

The form of pyelonephritis	Flow	Activity	The function of the kidneys
Primary. Secondary	Sharp. Chronic	The heat. The fading. Remission is incomplete. Complete remission	Saved. Partial violations. OPN. CRF
Obstructive. Dismetabolic. Obstructive metabolic

[9], [10], [11]

The long-term consequences of pyelonephritis in children

The frequency of recurrence of pyelonephritis in girls in the next year after the onset of the disease is 30%, and at 5 years - up to 50%. In boys, this probability is lower - about 15%. The threat of a recurrence of the disease increases significantly with narrowing of the urinary tract or in cases of urodynamic disorders. Nephrosclerosis occurs in 10-20% of patients with PN (the risk of its development directly depends on the frequency of recurrence). Obstructive uropathy or reflux alone can lead to the death of the parenchyma of the affected kidney, and when pyelonephritis is attached, the risk increases. According to numerous studies, it is pyelonephritis in children against a background of gross congenital anomalies of the urinary tract - the main cause of the development of terminal CRF. In cases of unilateral damage, the wrinkling of the kidney can lead to the development of hypertension, but the overall level of glomerular filtration does not suffer, as compensatory hypertrophy of the intact organ develops (in bilateral lesions, the risk of CRF is higher).

Pediatricians should remember that the long-term consequences of pyelonephritis - AH and CRN - do not necessarily occur in childhood, but can develop in adulthood (and in young and able-bodied). Women with pyelonephritic nephrosclerosis are at greater risk of pregnancy complications such as hypertension and nephropathy. According to a number of studies, the risk of nephrosclerosis increases with:

• obstruction of the urinary tract;
• vesicular-pulmonary reflux;
• frequent recurrence of pyelonephritis;
• inadequate treatment of exacerbations.

Laboratory signs of pyelonephritis in children

Bacterial leukocyturia is the main laboratory symptom of UTI (detection in the urine of predominantly neutrophilic leukocytes and bacteria). In the majority of patients in the period of heightening or exacerbation of PN, with a microscope of sediment,> 20 white blood cells are observed in the field of vision, but there is no direct relationship between their number and the severity of the disease.

Proteinuria is either absent or insignificant (<0.5-1 g / L). When pyelonephritis in children, it is not associated with a violation of the permeability of the glomerular barrier, but is caused by a disorder of the reverse absorption of the protein in the proximal tubules.

Erythrocyturia of different severity can arise in a number of patients, its causes are diverse:

• involvement in the inflammatory process of the mucous membrane of the bladder;
• urolithiasis disease;
• violation of the outflow of blood from the venous plexuses and their rupture, which occurs due to compression of the kidney vessels at the height of the activity of inflammation;
• the disturbed structure of the kidneys (polycystosis, vascular abnormalities);
• necrosis of the papilla of the kidney.

Hematuria does not serve as an argument for diagnosis of PN, but also does not allow it to be rejected (in such cases, an additional examination is needed to find out its causes).

Cilindrarium is a non-permanent symptom: they detect a small number of hyaline or leukocyte cylinders.

PH change in urine

Normally, an acidic urine reaction with UTI can change to a sharply alkaline one. However, a similar shift is observed in other conditions: the consumption of a large number of dairy and plant products, renal insufficiency, and damage to the renal tubules.

The decrease in the specific gravity of urine is typical for pyelonephritis in children with symptoms of impaired tubular functions (decreased ability to osmotic concentration). In acute pyelonephritis in children, such abnormalities are reversible; in chronic cases, they are of a persistent nature and can be combined with other signs of tubular disorders (glucosuria against normal plasma glucose concentration, electrolyte disturbances, metabolic acidosis).

General blood analysis

For children with pyelonephritis, inflammatory changes are typical: neutrophilic leukocytosis and an increase in ESR, anemia is possible. The severity of these disorders corresponds to the severity of general infectious symptoms.

Blood chemistry

Its changes (increase in the concentration of C-reactive protein, seromucoid) also reflect the severity of the inflammatory reaction. Signs of a violation of the nitrogen excretory function of the kidneys in acute pyelonephritis in children are rare, and in chronic cases they depend on the severity of nephrosclerosis.

[12], [13], [14], [15]

Study of the acid-base state of blood

Sometimes there is a tendency to metabolic acidosis - a manifestation of infectious toxicosis and a sign of impaired tubular function of the kidneys.

Ultrasound examination (ultrasound)

When it is carried out, in patients with PN sometimes enlargement of the pelvis, coarsening of the contour of the calyx, heterogeneity of the parenchyma with the areas of scarring (in the chronic form of the disease) are sometimes observed. Deferred symptoms of pyelonephritis in children include deformation of the kidney contour and a decrease in its size. Unlike glomerulonephritis, with PN these processes are asymmetric.

In excretory urography - sometimes a decrease in the tone of the upper urinary tract, flattened and rounded corners of the arches, narrowing and elongation of the cups. With the wrinkling of the kidney, the irregularity of its contours, the diminution of size, the thinning of the parenchyma are revealed. It should be noted that these changes are non-specific: they are observed in other nephropathies. The main task of visualizing methods in the examination of a patient with PN is to identify possible congenital anomalies of the urinary system as a soil for the development of the disease.

Ultrasound dopplerography (UZDG)

The study makes it possible to identify asymmetric disorders of renal blood flow in the development of cicatricial changes in organs.

Static nephroscintigraphy with pyelonephritis makes it possible to identify areas of dysfunctional tissue (with acute disease, these changes are reversible, and in chronic cases - stable). The detection of uneven asymmetric changes in the renal parenchyma with USD, nephroscintigraphy or renography in LV is important for differential diagnosis and prognosis.

Diagnosis of pyelonephritis in children

"Pyelonephritis" is mainly a laboratory diagnosis. As complaints of the patient, and data of objective research at PN are not specific and can be very scarce. When collecting an anamnesis by directed questions clarify the presence of such symptoms as temperature rises without catarrhal phenomena, episodes of impaired urination and pain in the abdomen and in the side. When conducting an examination, it is necessary to pay attention to:

• signs of intoxication;
• on the stigma of disembryogenesis (their large number, as well as visible abnormalities of the external genitalia, indicate a high probability of congenital anomalies, including the urinary system);
• on inflammatory changes in the external genitalia (the possibility of an ascending infection).

When pyelonephritis in children, it is possible to detect soreness in palpation of the abdomen along the ureters or in feces in the rib-vertebral corner. However, the above symptoms are nonspecific, and even a complete lack of findings in a physical examination does not allow you to reject the diagnosis before conducting a laboratory test.

The purpose of examination of a patient with suspected pyelonephritis:

• to confirm infection of the organs of the urinary system with the help of general analysis and bacteriological examination of urine (i.e.
• identify leukocyturia and bacteriuria, clarify their severity and change over time);
• evaluate the activity of the inflammatory process - general and biochemical analysis of blood, determination of proteins of the acute phase of inflammation;
• assess the function of the kidneys - determining the concentration of urea and creatinine in the blood serum, sampling Zimnitsky, etc .;
• identify factors predisposing to the disease - visualization of the organs of the urinary system, determination of urinary excretion of urine, functional studies of the lower urinary tract, etc.

A mandatory list of surveys for people with suspected pyelonephritis in children:

• urinalysis is general and quantitative (according to Kakowski-Addis and / or Nechiporenko), it is also desirable to conduct a urine sediment morphology study (uroleukogitogrammy) for detecting the predominant type of leukocytes;
• definition of bacteriuria. Representation of its presence can give colorimetric tests (with triphenyltetrazolium chloride, nitrite), based on the detection of metabolic products of breeding bacteria; however, the most important is bacteriological research, preferably three times. If the sample is obtained with natural urination, then detection of> 100 LLC of microbial bodies in 1 ml of urine is considered to be diagnostic, and if any number is found with catheterization or suprapubic urinary bladder puncture;
• biochemical blood test, determination of creatinine clearance;
• Zimnitsky's trial;
• Ultrasonography of kidney and bladder with determination of residual urine.

Additional methods of examination (for individual indications):

• Excretory urography - with suspected renal anomaly according to ultrasound;
• cystography - in situations with a high probability of detecting PLR (acute pyelonephritis in children under 3 years old, expansion of pelvis according to ultrasound, recurrent course of PN, complaints of persistent dysuria);
• cystoscopy - performed only after cystography with persistent complaints of dysuria, with HRD;
• additional study of the function of the renal tubules (urinary excretion of ammonia and titrated acids, electrolytes, samples with dryness and with water load, determination of osmolarity of urine);
• Functional methods of investigation of the lower urinary tract (determination of the rhythm of urination, urofluometry, cystomanometry, etc.) are performed with persistent dysuria;
• determination of the excretion of salts with urine (oxalates, urates, phosphates, calcium) is performed when large and aggregated crystals are detected in it or when kidney stones are detected;
• radionuclide studies (clarification of the degree of lesion of the parenchyma: scanning with 231 - sodium iodopyrupate, static nephroscintigraphy with 99тТс);
• determination of urinary excretion of beta2-microglobulin - a marker of tubular damage.

[16], [17], [18], [19], [20], [21]

Differential diagnosis of pyelonephritis in children

Because of the nonspecific clinical picture of pyelonephritis in children, differential diagnosis at the initial stage (before obtaining the results of laboratory studies) is very complicated. Abdominal pain in combination with fever often requires the exclusion of acute surgical pathology (most often acute appendicitis). In fact, with any fever without signs of respiratory failure and in the absence of other obvious local symptoms, pyelonephritis should be ruled out in children.

When there are changes in urinalysis, differential diagnosis is performed with the diseases listed below.

[22], [23], [24], [25], [26], [27]

Acute glomerulonephritis (OGN) with nephritic syndrome

Leukocyturia is a common symptom of this disease, but in typical cases it is insignificant and short-lived. Sometimes, especially in the debut of OGN, the number of neutrophils in the urine exceeds the number of erythrocytes (more than 20 cells in the field of view). Bacteria in the urine are not determined (abacterial leukocyturia). The more rapid disappearance of leukocytes from urine is characteristic than the normalization of protein concentration and the cessation of hematuria. Fever and dysuria with OGN are less common than with PN. For both diseases, complaints of pain in the abdomen and lower back are typical, however, unlike pyelonephritis, OGN is characterized by edema and AH.

[28], [29], [30], [31]

Abacterial interstitial nephritis (IN)

The immune damage of the basal membrane of the tubules is considered to be decisive in its development. It occurs for various reasons - toxic effects (drugs, heavy metals, radiation damage), metabolic shifts (impairment of urinary or oxalic acid metabolism), etc. The defeat of renal interstitium develops as in infectious diseases (viral hepatitis, infectious mononucleosis, diphtheria, hemorrhagic fever ), and with rheumatoid arthritis and gout, AH, after kidney transplantation. At IN, the clinical picture is also meager and nonspecific, with changes in laboratory tests: leukocyturia and signs of impaired tubular functions. However, unlike PN in the urine sediment, there are no bacteria and lymphocytes and / or eosinophils predominate.

[32], [33], [34], [35], [36], [37]

Tuberculosis of the kidneys

With a small but persistent leukocyturia, which does not decrease with the use of standard antibacterial drugs (especially with repeated negative bacteriological tests of urine), this disease should be excluded. Renal damage is the most common extrapulmonary form of tuberculosis. For him, as for PN, complaints of low back pain and dysuria, signs of intoxication, small proteinuria, changes in urine sediment (appearance of leukocytes and a small number of red blood cells) are typical. Differential diagnosis is complicated by the fact that in the early (parenchymal) phase of the disease there are no specific X-ray changes. To make a diagnosis, a special urine test is needed to determine the mycobacterium tuberculosis (standard methods do not detect them).

Infection of the lower urinary tract (cystitis)

According to the picture of urinalysis and according to the bacteriological study, the diseases are almost identical. Although approaches to their treatment are largely similar, but differential diagnosis is necessary, first, to determine the duration and intensity of antibiotic therapy and, secondly, to refine the prognosis (with cystitis there is no danger of damage to the kidney tissue). Acute diseases can be distinguished according to the clinical picture: in cystitis, the leading complaint is dysuria in the absence or low severity of the common infectious symptoms (the epithelium of the bladder has practically no resorptive capacity), therefore fever above 38 ° C and an increase in ESR of more than 20 mm / h make us think more about pyelonephritis, than about cystitis. Additional arguments in favor of acute PN - complaints of pain in the abdomen and in the waist, transient violations of the concentration ability of the kidneys.

In chronic course of UTI, the clinical picture of both diseases is not very symptomatic, which makes it difficult to recognize them and generates a problem of overdiagnosis (any recurrent infection is unambiguously regarded as chronic pyelonephritis). A significant role in determining the level of damage is played by signs of impaired renal tubule function. For their detection, in addition to Zimnitsky's standard test, loading tests for concentration and dilution, determination of osmolarity of urine, excretion of ammonia, titrated acids and electrolytes with urine are shown. A highly informative but costly method is to determine the content of beta2-microglobulin in the urine (this protein is normally re-adsorbed by 99% by the proximal tubules, and its increased secretion indicates their defeat). Radionuclide studies have also been shown to identify focal changes in the kidney parenchyma. It should be noted that even with a sufficiently complete examination in almost 25% of cases, it is difficult to accurately determine the level of the lesion.

Inflammatory diseases of external genital organs

Girls even have a significant leukocyturia (more than 20 cells in the field of vision), but without fever, dysuria, abdominal pain and without laboratory signs of inflammation always makes us think that the cause of changes in urine sediment is inflammation of the external genitalia. When confirming the diagnosis of vulvitis in such cases, it is advisable to prescribe a local treatment and repeat the urinalysis after the disappearance of the symptoms of the disease, rather than rush with the use of antibacterial drugs. However, with the above complaints, even in cases of obvious vulvitis, it is not worth throwing aside the possibility of developing an ascending infection. Similar tactics are justified in the inflammatory processes of the genitals in boys.

Treatment of pyelonephritis in children

Objectives of treatment

• Removal of bacteria from the urinary tract.
• Closing of clinical symptoms (fever, intoxication, dysuria).
• Correction of violations urodynamics.
• Prophylaxis of complications (nephrosclerosis, AH, CRF).

Treatment of pyelonephritis in children can be carried out both in hospital and outpatient settings. Absolute indications for hospitalization are the early age of the patient (younger than 2 years), severe intoxication, vomiting, dehydration symptoms, bacteremia and sepsis, severe pain syndrome. However, in most cases, the main reason for placing a GP patient in a hospital is the inability to conduct an adequate examination quickly on an outpatient basis. If there is such a possibility, then older children with a moderate course of the disease can be treated at home.

During the period of pyelonephritis, children are assigned a bed rest or sparing regimen (depending on the disruption of the general condition). Dietotherapy is aimed at shaking the tubular apparatus of the kidneys - restrict products containing excess protein and extractives, exclude salting, spices and vinegar, salt no more than 2-3 g / day (in the hospital - table number 5 according to Pevzner). With pyelonephritis (except in some cases), there is no need to exclude from the diet of the patient salt or animal protein. It is recommended to drink abundantly (50% more than the norm).

The main method of treatment of pyelonephritis in children is antibacterial therapy. The choice of the drug depends on both the isolated pathogen and the severity of the patient's condition, age, kidney and liver function, previous treatment, etc. Ideally, the definition of the sensitivity of bacteria to antibiotics in each specific case is considered, but in practice in clinically expressed UTI, treatment is in most cases prescribed empirically (at least at the initial stage). Proceed from the fact that in acute, emerging outside the hospital, PN is the most likely causative agent - E. Coli. If the disease develops after surgery or other manipulations on the urinary tract, the probability of identifying "problem" pathogens (for example, Pseudomonas aeruginosa) increases. When choosing drugs preference is given to antibiotics bactericidal, rather than static action. Urine collection should be carried out for bacteriological investigation as early as possible, since with the proper choice of medicine, bacteriuria disappears already on the 2-3rd day of treatment.

In addition to the general requirements for the antibiotic (its effectiveness in relation to the proposed pathogen and safety of use), in the treatment of pyelonephritis in children, the drug requires the ability to accumulate in the renal parenchyma in high concentrations. This requirement is met by cephalosporins of II-IV generations, amoxicillin + clavulanic acid, aminoglycosides, and fluoroquinolones. Other antibacterial agents (nitrofurantoin, non-fluorinated quinolones: nalidixic acid, nitroxoline-5-NOK, pipemidic acid-palin, phosphomycin) are excreted in the urine in fairly high concentrations, so they are effective in cystitis, but they are not used as starting therapy pyelonephritis in children. The E. Coli is resistant to aminopenicillins (ampicillin and amoxicillin), so they are undesirable as starting therapy drugs.

Thus, for the treatment of community-acquired pyelonephritis, "protected" penicillins (amoxicillin + clavulanic acid-augmentin, amoxiclav), cephalosporins of the II-IV generation (cefuroxime-zinatsef, cefoperazone-cefobide, ceftazidime-fortum, etc.) are considered as the first choice drugs for the first choice. Despite its potential nephro- and ototoxicity, aminoglycosides (gentamicin, tobramycin) retain their positions, but the use of these drugs requires monitoring of kidney function, which is possible only in a hospital. Aminoglycoside of the new generation - netilmicin has low toxicity, but because of its high cost it is rarely used. In severe PN (body temperature 39-40 ° C, severe intoxication), antibiotics are first administered parenterally, and when the condition improves, they switch to taking the drug of the same group per os ("stepwise" therapy). In mild cases, especially in older children, it is possible to prescribe an antibiotic orally at once. If within 3-4 days of clinical and laboratory effect of treatment is not, the drug is changed.

Antibacterial drugs of first choice for administration per os in outpatient settings

A drug	Daily dose, mg / kg	Multiplicity of application, once a day
Amoxicillin + clavulanic acid	20-30	3
Cefixim	8	2
Ceftibuten40	9	2
Cefaclor	25	3
Cefuroxime	250-500	2
Cephalexin	25	4

Antibacterial drugs of first choice for parenteral use 

A drug	Daily dose, mg / kg	Multiplicity of application, once a day
Amoxicillin + clavulanic acid	2-5	2
Ceftriaxone	50-80	1
Cefotaxime	150	4
Cefazolin	50	3
Gentamicin	2-5	2

Treatment of acute community-acquired pyelonephritis in children

Children under 3 years. Assign amoxicillin + clavulanic acid, cephalosporin II-III generation or aminoglycoside. The antibiotic is injected parenterally until the fever disappears, and then the medication is taken per os. The total duration of therapy is up to 14 days. After completion of the main course and before the cystography, a supportive treatment with uroseptic is prescribed. Cystography is performed for all patients regardless of the ultrasound data 2 months after remission is reached, since the probability of HRD at an early age is very high. Urography is carried out according to individual indications (suspicion of urinary tract obstruction according to ultrasound).

Children older than 3 years. Assign amoxicillin + clavulanic acid, cephalosporin II-III generation or aminoglycoside. In severe general condition, the antibiotic is administered parenterally, followed by a transition to per os, with a mild condition it is permissible to take the drug orally at once. In the absence of changes on sonograms, treatment is completed after 14 days. If ultrasound examination reveals an expansion of pelvis, then at the end of the main course, a maintenance treatment with uroseptics is prescribed before the cystography (it is performed 2 months after reaching remission). Urography is indicated for suspected renal anomalies according to ultrasound.

Preparations for maintenance therapy (taken once a night):

• amoxicillin + clavulanic acid - 10 mg / kg;
• co-trimoxazole [sulfamethoxazole + trimethoprim] - 2 mg / kg;
• furazidine (furagin) - 1 mg / kg.

Treatment of acute hospital (nosocomial) pyelonephritis in a child

Apply drugs effective against Pseudomonas aeruginosa, proteus, enterobacter, klebsiella (aminoglycosides, in particular netilmicin, cephalosporins of III-IV generation). Fluoroquinolones (ciprofloxacin, ofloxacin, norfloxacin), widely used in the treatment of adults, have numerous side effects (including unfavorable effects on the growth zones of cartilage), therefore in children under 14 years of age they are appointed in exceptional cases. Also, for special indications in severe cases, carbapenems (meropenem, imipenem), piperacillin + tazobactam, ticarcillin + clavulanic acid are used.

Treatment with several antibiotics is indicated in the following cases:

• severe septic flow of microbial inflammation (apostematous nephritis, kidney carbuncle);
• severe pyelonephritis caused by microbial associations;
• overcoming the multiple resistance of microorganisms to antibiotics, especially with "problem" infections caused by Pseudomonas aeruginosa, proteus, klebsiella, citrobacter.

The following drug combinations are used:

• "Protected" penicillins + aminoglycosides;
• cephalosporins III-IV generation + aminoglycosides;
• vancomycin + cephalosporins III-IV generation;
• vancomycin + amikacin.

Vancomycin is prescribed mainly with a confirmed staphylococcal or enterococcal nature of the disease.

Treatment of exacerbation of chronic pyelonephritis in a child is carried out on the same principles as acute. With a mild exacerbation, it can be performed on an outpatient basis with the appointment of protected penicillins, cephalosporins of the third generation per os. After elimination of the symptoms of exacerbation of chronic, and also after acute pyelonephritis, if urinary tract obstruction was diagnosed, the appointment of anti-relapse treatment for 4-6 weeks or more (up to several years) is indicated, its duration is determined individually.

Normalization of urodynamics is the second most important moment of treatment of pyelonephritis in children. Children older than 3 years are recommended a regime of compulsory urination with the emptying of the bladder every 2-3 hours (regardless of the urge). In obstructive pyelonephritis or PLR, the treatment is carried out together with a urologic surgeon (they decide on the catheterization of the bladder, surgical treatment). With neurogenic dysfunction of the bladder (after specifying its type), appropriate medical and physiotherapy treatment is performed. If they detect concrements, then together with the surgeon determine the indications for their rapid removal and correct metabolic disorders with diet, drinking regimen, drugs (pyridoxine, allopurinol, magnesium and citrate preparations, etc.).

Antioxidant therapy in the acute period is contraindicated, it is prescribed after the process activity subsides (after 5-7 days after initiation of antibiotic treatment). Apply vitamin E at a dose of 1-2 mg / (kgsut) or beta-carotene 1 drop per year of life for 4 weeks.

With PN, secondary mitochondrial dysfunction of tubular epithelial cells occurs, therefore, the appointment of levocarnitine, riboflavin, lipoic acid is indicated.

Immunocorrective therapy is prescribed according to strict indications: severe PN in young children; purulent lesions with multiple organ dysfunction syndrome; obstinately relapsing obstructive PN; resistance to antibiotic therapy; unusual composition of pathogens. The treatment is carried out after the process activity has died down. Apply Urovaksom, interferon alfa-2 preparations (viferon, reaferon), bifidobacteria bifidum + lysozyme, echinacea purpurea herb (immunal), lycopid.

Phytotherapy is performed during periods of remission. Assign herbs that have anti-inflammatory, antiseptic, regenerating effect: parsley leaves, kidney tea, mountaineer bird grass (sporich4), cowberry leaves, etc .; as well as finished preparations based on plant raw materials (phytolysin, kanefron H). However, it should be noted that the effectiveness of phytotherapy with PI is not confirmed.

Sanatorium treatment is possible only with the preservation of kidney function and not earlier than 3 months after the elimination of the symptoms of exacerbation. It is conducted in local sanatoriums or resorts with mineral waters (Zheleznovodsk, Essentuki, Truskavets).

Dispensary observation and prevention

Measures of primary prevention of pyelonephritis in children:

• regular emptying of the bladder;
• regular emptying of the intestine;
• sufficient fluid intake;
• hygiene of external genital organs, timely treatment of their inflammatory diseases;
• conducting ultrasound of the urinary system to all children under the age for timely detection and correction of anomalies. Similar measures are justified as prevention of exacerbations of pyelonephritis.

All children who have suffered at least one PN attack are subject to a follow-up visit of the nephrologist for 3 years, and if a urinary tract obstruction is found or the disease recurs, then permanently.

After the transferred acute non-obstructive PN for the first 3 months, urinalysis control tests are performed every 10-14 days, up to a year - monthly, and then - quarterly and after intercurrent diseases. Arterial pressure is controlled at each visit to the doctor. Once a year, the kidney function (Zimnitsky's test and determination of serum creatinine concentration) and ultrasound of the urinary system are performed. After 6 months after the disease, it is advisable to carry out static nephroscintrigraphy to identify possible scar changes in the kidney parenchyma.

If the pyelonephritis developed against the background of PLR, obstruction of the urinary tract, the patient is observed by the nephrologist and urologist together. In such cases, in addition to the above studies, repeated urography and / or cystography, nephroscintigraphy, cystoscopy, etc. (their frequency is determined individually, but on average - every 1-2 years). Such patients and persons with a single kidney pyelonephritis are at risk of developing CRF, they need a very careful and regular monitoring of the function of the organ. If its progressive decrease is fixed, then the patients are further observed together with specialists in hemodialysis and transplantation.

An important task for the pediatrician is to train the patient and his parents. They should pay attention to the importance of monitoring the regular emptying of the bladder and intestines, the need for prolonged preventive treatment (even with normal urinalysis results), the possibility of an unfavorable prognosis for pyelonephritis in children. In addition to the above, it is necessary to explain the importance of regular urine tests and fixation of their results, as well as timely recognition of the symptoms of exacerbation and / or disease progression.