Pyelonephritis in children

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

Urinary tract infections are the second most common after infectious respiratory diseases. About 20% of women suffer from them at least once in their lives. The disease often recurs (more than 50% of cases in girls and about 30% in boys). UTIs are distinguished with damage to:

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

Pyelonephritis is a non-specific acute or chronic microbial inflammation of the epithelium of the renal pelvis and calyceal system and the interstitium of the kidneys with secondary involvement of the tubules, blood and lymphatic vessels in the process.

Pyelonephritis in children is the most serious type of UTI according to prognosis; it requires timely diagnosis and adequate treatment, since when the renal interstitium is involved in the inflammatory process, there is a risk of their sclerosis and the development of formidable complications (renal failure, arterial hypertension).

It is difficult to determine the true proportion of pyelonephritis in children in the structure of all UTIs, since it is impossible to accurately determine the localization of the inflammatory process in almost a quarter of patients. Pyelonephritis, like UTIs in general, occurs in any age group: in the first 3 months of life, it is more common in boys, and at an older age it is approximately 6 times more common in females. This is due to the structural features of the female genitourinary system, allowing easy colonization of the urethra by microorganisms and the ascending spread of infection: the proximity of the external opening of the urethra to the anus and vagina, its short length and relatively large diameter, and the peculiar rotational movement of urine in it.

The incidence of pyelonephritis is characterized by three age peaks:

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

Pyelonephritis that occurs in early childhood often becomes chronic, worsening during puberty, at the beginning of sexual activity, during pregnancy or after childbirth.

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Causes of pyelonephritis in children

Pyelonephritis in children is a non-specific infectious disease, i.e. it is not characterized by any specific pathogen. In most cases, it is caused by gram-negative bacteria; usually, one type is detected in the urine (the presence of several most often indicates a violation of the urine collection technique).

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

Other intestinal microflora (Proteus, Pseudomonas aeruginosa, Klebsiella, Citrobacter, Senatia, Acinetobacter) - less often. Among the strains of Proteus, the most pathogenic are P. mirabilis, P. vulgaris, P. rettegri, P. morganii (they are detected in about 8% of children with pyelonephritis). Enterococcus and K. pneumoniae are detected with approximately the same frequency, and Enterobacter and S. aeruginosa - in 5-6% of cases (moreover, this pathogen causes persistent forms of pyelonephritis, it is often detected in the urine of people who have undergone surgery on 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. Given the above, when empirically prescribing treatment, it is assumed that pyelonephritis is caused by gram-negative bacteria.

Fungal pyelonephritis (e.g. caused by Candida albicans) is very rare and occurs mainly in individuals with immunodeficiency states. Non-colibacillary pyelonephritis occurs mainly 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 a term "complicated" or "problematic" UTI. Thus, the leading role in the development of the disease belongs to autoinfection with a predominance of intestinal microflora, less often - pyogenic coccal from nearby or distant inflammatory foci.

Despite the wide range of microorganisms capable of participating in the development of the inflammatory process in the kidneys, the mechanism of the effect of bacteria on the urinary system organs has been 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 defense system (these factors contribute to the long-term existence of bacteria in the body).
• O-antigen is part of the cell wall, has endotoxin properties and promotes microorganism adhesion.
• P-fimbriae are the thinnest mobile threads with special adhesin molecules. With their help, bacteria bind to glycolipid receptors of epithelial cells, which allows them to penetrate into the upper urinary tract even without vesicoureteral reflux (for example, E. coli with
• P-fimbriae are found in 94% of patients with proven pyelonephritis and only in 19% with cystitis).

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

A study of the relationship between E. coli pathogenicity factors and the course of UTI in children showed that bacteria with several pathogenicity factors are detected in pyelonephritis in children significantly more often (in 88% of cases) than in cystitis and asymptomatic bacteriuria (in 60 and 55%, respectively). Acute pyelonephritis is caused by various strains of E. coli, and chronic recurrent pyelonephritis is caused mainly by serogroups 0b and 02.

Bacteria that can survive in the human body for a long time are characterized by the following properties:

• antilysozyme activity - the ability to inactivate lysozyme (found in all types of enterobacteria and E. coli, as well as in 78.5% of Proteus 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, first and second generation cephalosporins).

When studying the pathogenicity of microorganisms isolated in various forms of UTI, it was found that children with transient bacteriuria have low-virulent bacteria in their urine, while those with transient bacteriuria have highly virulent bacteria.

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How does pyelonephritis develop in a child?

The main routes of infection penetration into the kidney are:

• hematogenous - observed in rare cases (more often in newborns with sepsis caused by Staphylococcus aureus, less often in older children against the background of systemic infections with bacteremia), the development of embolic nephritis (apostematous or renal carbuncle) is possible, when circulating microorganisms are retained in the glomeruli and lead to the formation of abscesses in the cortex;
• ascending - main.

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

• hydrodynamic protection (regular and complete emptying of the bladder) - mechanical removal of bacteria;
• glycoproteins that prevent the attachment of bacteria to the mucous membrane (uromucoid, which reacts with E. coli fimbriae);
• humoral and cellular immunity (IgA, IgG, neutrophils and macrophages);
• low urine pH and fluctuations in its osmolarity.

In boys during puberty, the secretion of the prostate gland, which has bacteriostatic properties, also plays a protective role.

Transient disruption of local protective factors may be a consequence of microcirculation defects in the bladder wall during hypothermia or after an acute respiratory viral infection. In neurogenic dysfunction of the bladder, accumulation of residual urine disrupts hydrodynamic protection and promotes the attachment of bacteria to the mucous membrane of the bladder and ureters.

The sources of bacteria entering the urinary tract are the colon, vagina or foreskin, so the risk of pyelonephritis in children increases with intestinal dysbacteriosis and inflammatory diseases of the external genitalia. Antibiotic treatment (for example, for respiratory infections) can lead not only to intestinal dysbacteriosis, but also to a change in the composition of the vaginal or foreskin microflora: to the suppression of saprophytic strains and the appearance of uropathogenic bacteria. Constipation also predisposes to a violation of the intestinal biocenosis in a child.

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

• the initially existing obstruction to the outflow of urine is mechanical (congenital - hydronephrosis, urethral valve; acquired - urolithiasis or dysmetabolic nephropathy with crystalluria, leading to micro-obstruction at the level of the tubules even without stone formation) or functional (neurogenic dysfunction of the bladder);
• Vesicoureteral reflux (VPR) is a retrograde flow of urine into the upper urinary tract due to failure of the vesicoureteral junction.

Thus, 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 a microbial inflammatory process in the kidneys, in addition to the listed factors, the state of the body's immune system is important. It has been established that the occurrence of urinary tract infections is facilitated by a deficiency of secretory IgA, as well as changes in vaginal pH, disrupted hormonal profile, recent infections and intoxications. In children who have had UTIs in the neonatal period, concomitant purulent-inflammatory diseases, intestinal dysbacteriosis, hypoxic encephalopathy, and signs of morphofunctional immaturity are often detected. Frequent acute respiratory viral infections, rickets, atopic dermatitis, iron deficiency anemia, and intestinal dysbacteriosis are typical for children who have developed pyelonephritis at the age of 1 month to 3 years.

In the development of pyelonephritis with an ascending path of penetration of the pathogen, several stages are distinguished. Initially, the distal parts of the urethra are infected. Later, the infection spreads to the bladder, from where the bacteria penetrate the renal pelvis and kidney tissue (largely due to PLR) and colonize them. Microorganisms that have penetrated the renal parenchyma cause an inflammatory process (it largely depends on the characteristics of the body's immune system). In this process, the following points can be distinguished:

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

The consequence of the above processes is an inflammatory reaction (neutrophilic infiltration with varying degrees of exudative component is characteristic of the initial stages, and lymphohistiocytes predominate in subsequent stages). The experiment showed that in the first hours after bacteria enter the kidney, processes similar to those in the shock lung occur: activation of complement components, which leads to platelet and granulocyte aggregation; cytolytic tissue damage (direct and mediated by inflammation mediators). The described processes lead to ischemic necrosis of kidney tissue in the first 48 hours of the disease. Tissue damaged in this way is easily infected with bacteria, and, ultimately, microabscesses occur. Without adequate treatment, renal blood flow decreases and the volume of functioning parenchyma decreases. In the chronic course of the process, as it progresses, the synthesis of "antirenal" antibodies and the formation of specific T-killers sensitized to renal tissue are noted. Ultimately, progressive nephron death can lead to interstitial sclerosis and the development of chronic kidney disease (CKD).

Pathological anatomy

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

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

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

Serous inflammation (most cases of pyelonephritis) - edema and leukocyte infiltration of the interstitium. Multinucleated cells are found in edematous areas and in the lumen of the tubules. The glomeruli are usually unchanged. Inflammation affects the kidney unevenly, and the affected areas may be adjacent to normal tissue. Infiltration zones are located mainly around the collecting tubules, although they are sometimes found in the cortex. The process ends with scarring, which makes it possible to talk about the irreversibility of changes even in acute pyelonephritis.

Chronic pyelonephritis in children. The changes are mainly represented by unevenly expressed mononuclear cell infiltration and focal sclerosis of the parenchyma. During the period of exacerbation, exudate containing multinucleated cells is found in the interstitium. The process is completed by atrophy of the tubules and their replacement 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).

As pyelonephritis progresses, interstitial sclerosis develops, i.e., proliferation of connective tissue in the interstitium, which also leads to scarring of the glomeruli and a progressive decrease in renal function. One of the main signs of pyelonephritis, which distinguishes it from other tubulointerstitial lesions, is changes in the epithelium of the calyces and pelvis: signs of acute (edema, impaired microcirculation, neutrophil infiltration) or chronic inflammation (lymphohistiocytic infiltration, sclerosis).

Symptoms of pyelonephritis in children

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

• general infectious - increase in body temperature to 38 °C, chills, intoxication (headache, vomiting, loss of appetite), possible pain in muscles and joints;
• local - frequent painful urination when the infection spreads in an ascending manner (when the mucous membrane of the bladder is involved in the inflammatory process), pain in the abdomen, side and lower back (they are caused by stretching of the kidney capsule with parenchyma edema).

In the first year of life, general infectious symptoms predominate in the clinical picture. Infants with PN often experience regurgitation and vomiting, loss of appetite, upset stool, pale-gray skin; signs of neurotoxicosis and meningeal symptoms may appear with high fever. Older children complain of abdominal pain in 2/3 of cases, usually in the periumbilical region (radiating from the diseased organ to the solar plexus). The pain may radiate along the ureter to the thigh and groin. The pain syndrome is usually mild or moderate, its increase is noted with involvement of the perirenal tissue in the inflammatory process (with relatively rare staphylococcal PN) or with impaired urine outflow.

Exacerbation of chronic pyelonephritis in children sometimes occurs with scanty symptoms. In the latter case, only targeted collection of anamnesis allows us to identify complaints of mild pain in the lumbar region, episodes of "unmotivated" subfebrile temperature, latent urination disorders (imperative urges, occasionally enuresis). Often the only complaints are manifestations of infectious asthenia - pale skin, increased fatigue, decreased appetite, in young children - weight loss and growth retardation.

Edema syndrome is not typical for pyelonephritis. On the contrary, during periods of exacerbation, signs of exsicosis are sometimes noted both due to fluid loss due to fever and vomiting, and due to a decrease in the concentration function of the kidneys and polyuria. Nevertheless, slight pastosity of the eyelids is sometimes noticeable in the morning (it occurs due to disturbances in the regulation of water-electrolyte balance).

Arterial pressure in acute pyelonephritis does not change (unlike the onset of acute glomerulonephritis, which often occurs with its increase). Arterial hypertension (AH) is a companion and complication primarily of chronic PN in cases of nephrosclerosis and progressive decline in organ function (in such cases, AH is often persistent and can acquire a malignant character).

In general, the symptoms of pyelonephritis in children are not very specific, and laboratory symptoms, especially changes in the general urine analysis and the results of bacteriological examination, play a decisive role in its diagnosis.

Classification of pyelonephritis in children

There is no single classification of PN used worldwide. According to the 1980 classification adopted in domestic pediatrics, the following forms of pyelonephritis are distinguished:

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

Depending on the course of the process, a distinction is made between:

• acute pyelonephritis in children;
• Chronic pyelonephritis in children is a protracted (longer than 6 months) or recurrent disease.

Moreover, in chronic PN, exacerbations are caused by the same strain of bacteria, and if another is detected, the disease is regarded as a repeated episode of acute PN.

Phases of pyelonephritis:

• in acute renal failure - peak, abate and remission;
• in chronic PN - exacerbation, incomplete (clinical) remission (there are no clinical and laboratory signs of inflammatory activity, but there are changes in urine tests) and complete (clinical and laboratory) remission (no changes in urine tests).

Classification of any kidney disease contains a characteristic of their functional state. In acute renal failure or in the exacerbation of chronic renal failure, renal function may be preserved, sometimes its partial impairments are noted (primarily a change in concentration ability), and the development of acute or chronic renal failure is also possible.

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

Form of pyelonephritis	Flow	Activity	Kidney function
Primary. Secondary.	Acute. Chronic.	Peak. Subsidence. Incomplete remission. Complete remission.	Preserved. Partial disorders. ARF. CRF
Obstructive. Dysmetabolic. Obstructive-metabolic.

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Remote consequences of pyelonephritis in children

The recurrence rate 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 risk of recurrence of the disease increases significantly with narrowing of the urinary tract or with urodynamic disorders. Nephrosclerosis occurs in 10-20% of patients with renal failure (the risk of its development directly depends on the frequency of recurrence). Obstructive uropathy or reflux in themselves can lead to the death of the parenchyma of the affected kidney, and with the addition of pyelonephritis, the risk increases. According to numerous studies, it is pyelonephritis in children against the background of gross congenital anomalies of the urinary tract that is the main cause of the development of terminal CRF. In cases of unilateral damage, kidney shrinkage can lead to the development of hypertension, but the overall level of glomerular filtration does not suffer, since compensatory hypertrophy of the undamaged organ develops (with bilateral damage, the risk of developing chronic renal failure is higher).

The pediatrician should remember that the remote consequences of pyelonephritis - hypertension and chronic renal failure - do not necessarily occur in childhood, but can develop in adulthood (and in young and able-bodied adults). Women with pyelonephritic nephrosclerosis are at greater risk of developing pregnancy complications such as hypertension and nephropathy. According to a number of studies, the risk of nephrosclerosis increases with:

• urinary tract obstruction;
• vesicoureteral 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 urine of predominantly neutrophilic leukocytes and bacteria). In most patients during the peak or exacerbation of PN, microscopic examination of sediment reveals >20 leukocytes per 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). In pyelonephritis in children, it is not associated with a violation of the permeability of the glomerular barrier, but is caused by a disorder of protein reabsorption in the proximal tubules.

Erythrocyturia of varying severity can occur in a number of patients, its causes are varied:

• involvement of the mucous membrane of the bladder in the inflammatory process;
• urolithiasis;
• disruption of blood outflow from the venous plexuses and their rupture, which occurs as a result of compression of the renal vessels at the height of inflammation activity;
• abnormal kidney structure (polycystic disease, vascular anomalies);
• renal papilla necrosis.

Hematuria does not serve as an argument for making a diagnosis of PN, but it also does not allow one to reject it (in such cases, additional examination is necessary to determine its causes).

Cylindruria is an inconstant symptom: a small number of hyaline or leukocyte casts are detected.

Changes in urine pH

Normally, the acidic reaction of urine during UTI can change to a sharply alkaline reaction. However, a similar shift is also observed in other conditions: consumption of large amounts of dairy and plant products, renal failure, and damage to the renal tubules.

A decrease in the specific gravity of urine is a typical symptom of tubular dysfunction for pyelonephritis in children (reduced ability for osmotic concentration). In acute pyelonephritis in children, such disorders are reversible, while in chronic pyelonephritis, they are persistent and can be combined with other signs of tubular dysfunction (glucosuria against the background of normal glucose concentration in blood plasma, electrolyte disorders, metabolic acidosis).

Complete blood count

Pyelonephritis in children is characterized by inflammatory changes - neutrophilic leukocytosis and increased ESR, anemia is possible. The severity of these disorders corresponds to the severity of general infectious symptoms.

Biochemical blood test

Its changes (increased concentration of C-reactive protein, seromucoid) also reflect the severity of the inflammatory reaction. Signs of impaired nitrogen-excreting function of the kidneys in acute pyelonephritis in children are rarely detected, and in chronic pyelonephritis they depend on the severity of nephrosclerosis.

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Blood acid-base balance study

Sometimes a tendency to metabolic acidosis is noted - a manifestation of infectious toxicosis and a sign of impaired renal tubular function.

Ultrasound examination (ultrasound)

When it is performed in patients with PN, dilation of the renal pelvis, coarsening of the cup contour, heterogeneity of the parenchyma with areas of scarring (in the chronic form of the disease) are sometimes observed. Delayed symptoms of pyelonephritis in children include deformation of the kidney contour and a decrease in its size. Unlike glomerulonephritis, in PN, these processes are asymmetrical.

During excretory urography, a decrease in the tone of the upper urinary tract, flattening and rounding of the angles of the vaults, narrowing and elongation of the calyces are sometimes noted. When the kidney is shriveled, its contours are uneven, its size is reduced, and the parenchyma is thinned. It should be noted that these changes are non-specific: they are also observed in other nephropathies. The main task of visualization methods when examining a patient with PN is to identify possible congenital anomalies of the urinary system as a basis for the development of the disease.

Ultrasound Dopplerography (USDG)

The study allows us to identify asymmetrical disturbances in renal blood flow during the development of cicatricial changes in the organs.

Static nephroscintigraphy in pyelonephritis allows to identify areas of non-functioning tissue (in acute disease, the indicated changes are reversible, and in chronic disease, they are stable). Detection of uneven asymmetric changes in the renal parenchyma using ultrasound Doppler imaging, nephroscintigraphy or renography in PN is important for differential diagnosis and prognosis.

Diagnosis of pyelonephritis in children

"Pyelonephritis" is primarily a laboratory diagnosis. Both the patient's complaints and the objective examination data for PN are non-specific and can be very scanty. When collecting anamnesis, targeted questions clarify the presence of symptoms such as temperature increases without catarrhal symptoms, episodes of impaired urination, and pain in the abdomen and side. When conducting an examination, it is necessary to pay attention to:

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

In children with pyelonephritis, pain may be detected during abdominal palpation along the ureters or during percussion in the costovertebral angle. However, the above symptoms are nonspecific, and even a complete absence of findings during physical examination does not allow one to reject the diagnosis before conducting a laboratory study.

The purpose of examining a patient with suspected pyelonephritis:

• confirm urinary tract infection with a general urine analysis and bacteriological examination (i.e.
• identify leukocyturia and bacteriuria, clarify their severity and changes over time);
• assess the activity of the inflammatory process - general and biochemical blood tests, determination of acute phase inflammation proteins;
• assess kidney function - determine the concentration of urea and creatinine in the blood serum, perform the Zimnitsky test, etc.;
• identify factors predisposing to the disease - conducting visual examinations of the urinary system, determining the excretion of salts in the urine, functional studies of the lower urinary tract, etc.

Mandatory list of examinations for individuals with suspected pyelonephritis in children:

• general and quantitative urine tests (according to Kakovsky-Addis and/or Nechiporenko), it is also advisable to conduct a study of the morphology of urine sediment (uroleukocytogram) to identify the predominant type of leukocytes;
• determination of bacteriuria. An idea of its presence can be given by colorimetric tests (with triphenyltetrazolium chloride, nitrite), based on the detection of metabolic products of multiplying bacteria; however, bacteriological examination, preferably three times, is of the utmost importance. If the sample is obtained during natural urination, then the detection of >100,000 microbial bodies in 1 ml of urine is considered diagnostically significant, and if during catheterization or suprapubic puncture of the bladder - any number of them;
• biochemical blood test, determination of creatinine clearance;
• Zimnitsky's test;
• Ultrasound of the kidneys and bladder with determination of residual urine.

Additional examination methods (according to individual indications):

• excretory urography - if a kidney abnormality is suspected based on ultrasound data;
• cystography - in situations with a high probability of detecting PLR (acute pyelonephritis in children under 3 years of age; dilation of the renal pelvis according to ultrasound data; recurrent course of PN; complaints of persistent dysuria);
• cystoscopy - performed only after cystography in case of persistent complaints of dysuria, in case of PLR;
• additional examination of renal tubule function (urinary excretion of ammonia and titratable acids, electrolytes, dry food and water load tests, determination of urine osmolarity);
• functional methods of examination of the lower urinary tract (determination of the rhythm of urination, uroflowmetry, cystomanometry, etc.) are carried out in case of persistent dysuria;
• determination of the excretion of salts in urine (oxalates, urates, phosphates, calcium) is carried out when large and aggregated crystals are detected in it or when kidney stones are detected;
• radionuclide studies (to clarify the degree of parenchyma damage: scanning with 231-sodium iodohippurate; static nephroscintigraphy with 99mTc);
• determination of urinary excretion of beta2-microglobulin, a marker of tubular damage.

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Differential diagnostics of pyelonephritis in children

Due to the non-specificity of the clinical picture of pyelonephritis in children, differential diagnostics at the initial stage (before receiving the results of laboratory tests) is very difficult. Abdominal pain in combination with fever often requires exclusion of acute surgical pathology (most often - acute appendicitis). In fact, with any fever without signs of respiratory tract damage and in the absence of other obvious local symptoms, it is necessary to exclude pyelonephritis in children.

If changes are detected in urine tests, differential diagnostics are carried out with the diseases listed below.

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Acute glomerulonephritis (AGN) with nephritic syndrome

Leukocyturia is a common symptom of this disease, but in typical cases it is insignificant and short-lived. Sometimes, especially at the onset of AGN, the number of neutrophils in the urine exceeds the number of erythrocytes (more than 20 cells in the field of view). Bacteria are not detected in the urine (abacterial leukocyturia). Typically, leukocytes disappear from the urine more quickly than the normalization of protein concentration and the cessation of hematuria. Fever and dysuria are less common in AGN than in PN. Both diseases are characterized by complaints of abdominal and lumbar pain, however, unlike pyelonephritis, AGN is characterized by edema and hypertension.

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Abacterial interstitial nephritis (IN)

The immune damage to the tubular basement membrane is considered to be the determining factor in its development. It occurs for various reasons - toxic effects (medicines, heavy metals, radiation damage), metabolic changes (impaired uric or oxalic acid metabolism), etc. Damage to the renal interstitium develops both in infectious diseases (viral hepatitis, infectious mononucleosis, diphtheria, hemorrhagic fever), and in rheumatoid arthritis and gout, hypertension, after kidney transplantation. With IN, the clinical picture is also scanty and nonspecific, characterized by changes in laboratory tests: leukocyturia and signs of impaired tubular function. However, unlike PN, there are no bacteria in the urine sediment and lymphocytes and / or eosinophils predominate.

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Tuberculosis of the kidneys

In case of slight but persistent leukocyturia that does not decrease with the use of standard antibacterial drugs (especially with repeated negative results of bacteriological examination of urine), the above disease should be excluded. Kidney damage is the most common extrapulmonary form of tuberculosis. For it, as for renal failure, complaints of back pain and dysuria, signs of intoxication, slight proteinuria, changes in urine sediment (the appearance of leukocytes and a small number of erythrocytes) are characteristic. Differential diagnostics is complicated by the fact that in the early (parenchymatous) phase of the disease there are no specific radiological changes yet. To establish a diagnosis, a special urine test is necessary to determine mycobacteria tuberculosis (they are not detected by standard methods).

Lower urinary tract infection (cystitis)

According to the urine analysis picture and the bacteriological examination data, the diseases are practically identical. Although the approaches to their treatment are largely similar, differential diagnostics is necessary, firstly, to determine the duration and intensity of antibacterial therapy and, secondly, to clarify the prognosis (with cystitis, there is no risk of damage to the renal tissue). Acute diseases can be distinguished by the clinical picture: with cystitis, the leading complaint is dysuria in the absence or slight expression of general infectious symptoms (the epithelium of the bladder has virtually no resorptive capacity), therefore, fever above 38 °C and an increase in ESR of more than 20 mm / h make one think more about pyelonephritis than about cystitis. Additional arguments in favor of acute renal failure are complaints of pain in the abdomen and lower back, transient disturbances in the concentration capacity of the kidneys.

In chronic UTI, the clinical picture of both diseases is asymptomatic, which complicates their recognition and creates the problem of overdiagnosis (any recurrent infection is definitely regarded as chronic pyelonephritis). Signs of renal tubular dysfunction play a major role in determining the level of damage. In addition to the standard Zimnitsky test, loading tests for concentration and dilution, determination of urine osmolarity, excretion of ammonia, titratable acids and electrolytes with urine are indicated for their detection. A highly informative but expensive method is determination of the beta2-microglobulin content in urine (this protein is normally 99% reabsorbed by the proximal tubules, and its increased excretion indicates their damage). Radionuclide studies are also indicated for detection of focal changes in the renal parenchyma. It should be noted that even with a fairly complete examination, in almost 25% of cases it is difficult to accurately determine the level of damage.

Inflammatory diseases of the external genitalia

In girls, even 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 one 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 local treatment and repeat the urine test after the symptoms of the disease disappear, and not to rush to use antibacterial drugs. However, with the above complaints, even in cases of obvious vulvitis, one should not discard the possibility of developing an ascending infection. Similar tactics are justified in inflammatory processes of the genitals in boys.

Treatment of pyelonephritis in children

Treatment goals

• Removing bacteria from the urinary tract.
• Relief of clinical symptoms (fever, intoxication, dysuria).
• Correction of urodynamic disorders.
• Prevention of complications (nephrosclerosis, hypertension, chronic renal failure).

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 (under 2 years), severe intoxication, vomiting, symptoms of dehydration, bacteremia and sepsis, severe pain syndrome. However, in most cases, the main reason for placing a patient with pyelonephritis in hospital is the impossibility of conducting a proper examination quickly enough in an outpatient setting. If such an opportunity exists, then older children with a moderate course of the disease can be treated at home.

During the period of active pyelonephritis in children, bed rest or a gentle regimen is prescribed (depending on the general condition). Diet therapy is aimed at sparing the renal tubular apparatus - limiting foods containing excess protein and extractive substances, excluding pickles, spices and vinegar, salt no more than 2-3 g / day (in hospital - table No. 5 according to Pevzner). With pyelonephritis (except for individual cases), there is no need to exclude salt or animal protein from the patient's diet. Plenty of fluids are recommended (50% more than the age norm).

The main method of treating pyelonephritis in children is antibacterial therapy. The choice of drug depends on the isolated pathogen, the severity of the patient's condition, his age, kidney and liver function, previous treatment, etc. Determining the sensitivity of bacteria to antibiotics in each specific case is considered ideal, but in practice, with clinically expressed UTI, treatment is prescribed empirically in most cases (at least at the initial stage). It is assumed that in acute pyelonephritis that occurs outside the hospital, the most likely pathogen is E. coli. If the disease developed after surgery or other manipulations on the urinary tract, the likelihood of isolating "problematic" pathogens (for example, Pseudomonas aeruginosa) increases. When choosing drugs, preference is given to antibiotics with bactericidal rather than static action. Urine should be collected for bacteriological examination as early as possible, since with the correct choice of drug, bacteriuria disappears already on the 2-3rd day of treatment.

In addition to the general requirements for an antibiotic (its effectiveness against the suspected pathogen and safety of use), when treating pyelonephritis in children, the drug must be able to accumulate in the renal parenchyma in high concentrations. This requirement is met by cephalosporins of the II-IV generations, amoxicillin + clavulanic acid, aminoglycosides, and fluoroquinolones. Other antibacterial agents (nitrofurantoin; non-fluorinated quinolones: nalidixic acid, nitroxoline - 5-NOC; pipemidic acid - palin; fosfomycin) are excreted from the body with urine in fairly high concentrations, so they are effective in cystitis, but they are not used as initial therapy for pyelonephritis in children. E. coli is resistant to aminopenicillins (ampicillin and amoxicillin), so they are undesirable as initial therapy drugs.

Thus, for the treatment of community-acquired pyelonephritis, the first-choice drugs are considered to be "protected" penicillins (amoxicillin + clavulanic acid - augmentin, amoxiclav), cephalosporins of the II-IV generation (cefuroxime - zinacef, cefoperazone - cefobid, ceftazidime - fortum, etc.). Despite their 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. The new generation aminoglycoside - netilmicin has low toxicity, but due to its high cost it is rarely used. In severe cases of 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 ("step" therapy). In mild cases, especially in older children, it is possible to immediately prescribe an antibiotic orally. If there is no clinical or laboratory effect from the treatment within 3-4 days, the drug is changed.

Antibacterial drugs of first choice for oral administration in outpatient settings

Preparation	Daily dose, mg/kg	Frequency of use, once a day
Amoxicillin + clavulanic acid	20-30	3
Cefixime	8	2
Ceftibuten40	9	2
Cefaclor	25	3
Cefuroxime	250-500	2
Cephalexin	25	4

First-line antibacterial drugs for parenteral use

Preparation	Daily dose, mg/kg	Frequency of use, 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 of age. Amoxicillin + clavulanic acid, cephalosporin of the second or third generation, or aminoglycoside are prescribed. The antibiotic is administered parenterally until the fever disappears, then the drug is taken orally. The total duration of therapy is up to 14 days. Upon completion of the main course and before cystography, maintenance treatment with uroseptics is prescribed. Cystography is performed on all patients, regardless of ultrasound data, 2 months after achieving remission, since the probability of PLR at an early age is very high. Urography is performed according to individual indications (suspected obstruction of the urinary tract according to ultrasound data).

Children over 3 years old. Amoxicillin + clavulanic acid, cephalosporin II-III generation or aminoglycoside are prescribed. In severe general condition, the antibiotic is administered parenterally with subsequent transition to per os administration; in mild condition, it is permissible to immediately take the drug orally. If there are no changes in sonograms, treatment is completed after 14 days. If ultrasound reveals dilation of the renal pelvis, then after completion of the main course, maintenance treatment with uroseptics is prescribed until cystography is performed (it is performed 2 months after achieving remission). Urography is indicated if a renal anomaly is suspected based on ultrasound data.

Maintenance therapy drugs (taken once at night):

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

Treatment of acute hospital-acquired pyelonephritis in a child

Drugs effective against Pseudomonas aeruginosa, Proteus, Enterobacter, Klebsiella are used (aminoglycosides, in particular netilmicin; cephalosporins of the III-IV generation). Fluoroquinolones (ciprofloxacin, ofloxacin, norfloxacin), widely used in the treatment of adults, have numerous side effects (including adverse effects on cartilage growth zones), so they are prescribed to children under 14 years of age in exceptional cases. Also, according to special indications in severe cases, carbapenems (meropenem, imipenem), piperacillin + tazobactam, ticarcillin + clavulanic acid are used.

Treatment with multiple antibiotics is indicated in cases of:

• severe septic course of microbial inflammation (apostematous nephritis, renal carbuncle);
• severe course of pyelonephritis caused by microbial associations;
• overcoming multiple resistance of microorganisms to antibiotics, especially in “problematic” infections caused by Pseudomonas aeruginosa, Proteus, Klebsiella, and Citrobacter.

The following combinations of drugs are used:

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

Vancomycin is prescribed mainly when the disease is confirmed to be of staphylococcal or enterococcal origin.

Treatment of exacerbation of chronic pyelonephritis in a child is carried out according to the same principles as acute. In case of a mild exacerbation, it can be carried out on an outpatient basis with the prescription of protected penicillins, third-generation cephalosporins per os. After the elimination of symptoms of exacerbation of chronic, as well as after acute pyelonephritis, if obstruction of the urinary tract was diagnosed, the prescription 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. For children over 3 years old, a regime of forced urination with emptying of the bladder every 2-3 hours (regardless of the urge). In case of obstructive pyelonephritis or PLR, treatment is carried out jointly with a urologist surgeon (they decide on catheterization of the bladder, surgical treatment). In case of neurogenic dysfunction of the bladder (after specifying its type), appropriate drug and physiotherapeutic treatment is carried out. If stones are detected, then together with the surgeon they determine the indications for their surgical removal and correct metabolic disorders with the help of diet, drinking regimen, drugs (pyridoxine, allopurinol, magnesium and citrate preparations, etc.).

Antioxidant therapy is contraindicated in the acute period; it is prescribed after the process activity has subsided (5-7 days after the start of antibiotic treatment). Vitamin E is used at a dose of 1-2 mg/(kg/day) or beta-carotene, 1 drop per year of life for 4 weeks.

In PN, secondary mitochondrial dysfunction of tubular epithelial cells occurs, therefore, the administration of levocarnitine, riboflavin, and lipoic acid is indicated.

Immunocorrective therapy is prescribed according to strict indications: severe PN in young children; purulent lesions with multiple organ failure syndrome; persistently recurring obstructive PN; resistance to antibiotic therapy; unusual composition of pathogens. Treatment is carried out after the activity of the process has subsided. Urovaxom, interferon alpha-2 preparations (Viferon, Reaferon), bifidobacteria bifidum + lysozyme, purple echinacea herb (immunal), likopid are used.

Phytotherapy is carried out during periods of remission. Prescribed herbs have anti-inflammatory, antiseptic, regenerating effects: parsley leaves, kidney tea, knotweed grass (knotweed4), lingonberry leaves, etc.; as well as ready-made preparations based on plant materials (phytolysin, canephron N). However, it should be noted that the effectiveness of phytotherapy for PN has not been confirmed.

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

Outpatient observation and prevention

Primary prevention measures for pyelonephritis in children:

• regular emptying of the bladder;
• regular bowel movements;
• adequate fluid intake;
• hygiene of the external genitalia, timely treatment of their inflammatory diseases;
• Conducting ultrasound examination of the urinary system for all children under one year of age for timely detection and correction of anomalies. Similar measures are justified as a preventive measure for exacerbations of pyelonephritis.

All children who have suffered at least one attack of urinary incontinence are subject to dispensary observation by a nephrologist for 3 years, and if obstruction of the urinary tract is detected or the disease recurs, then permanently.

After acute non-obstructive renal failure, urine tests are performed every 10-14 days for the first 3 months, monthly for up to a year, and then quarterly and after intercurrent illnesses. Blood pressure is monitored at each visit to the doctor. Renal function is tested once a year (Zimnitsky test and determination of serum creatinine concentration) and ultrasound of the urinary system. Six months after the disease, it is advisable to perform static nephroscintrigraphy to detect possible cicatricial changes in the renal parenchyma.

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

An important task of the pediatrician is to educate the patient and his parents. They should be drawn to the importance of monitoring regular emptying of the bladder and bowels, the need for long-term preventive treatment (even with normal urine test results), and 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 recording their results, as well as timely recognition of symptoms of exacerbation and/or progression of the disease.