Gestational pyelonephritis

Pyelonephritis is a non-specific infectious and inflammatory process with a predominant initial lesion of the interstitial tissue, the renal pelvis and tubules, followed by involvement of the glomeruli and renal vessels in the pathological process.

The inflammatory process in the kidneys that occurs during pregnancy is called "gestational pyelonephritis".

Epidemiology

Urinary tract infections are the most common diseases during pregnancy, including in apparently healthy women with normal kidney function and no structural changes in the urinary tract in the prenatal period.

Worldwide, pyelonephritis is one of the most common manifestations of infection during pregnancy. [ 1 ] Pyelonephritis complicates 1 to 2% of all pregnancies; [ 2 ] its incidence depends on the prevalence of asymptomatic bacteriuria in the population. Pyelonephritis occurs mainly in the second and third trimesters, with about 10-20% occurring in the first trimester. [ 3 ]

Pyelonephritis can lead to preterm birth in 20–30% of women, and these babies are at high risk of neonatal mortality.[ 4 ],[ 5 ]

Causes gestational pyelonephritis

The types of microorganisms that cause urinary tract infections are similar in pregnant and non-pregnant women, confirming the common mechanisms of infection penetration into the urinary tract.

The etiology of gestational pyelonephritis is directly related to the obligate and facultative intestinal microflora. The most common pathogens are bacteria of the Enterobacteriaceae family, of which Escherichia coli accounts for up to 80–90%. The importance of other microorganisms: both gram-negative (Proteus, Klebsiella, Enterobacter, Pseudomonas, Serratia) and gram-positive (Enterococcus faecalis, Staphylococcus sp. (saprophyticus and aureus) bacteria - increases significantly in the case of hospital infection.

Rare pathogens may include fungi of the genera Candida, stronglastomyces, and pathogens of sexually transmitted diseases (Chlamydia trachomatis, Neisseria gonorrhoeae).

Viruses are not considered independent etiological factors, but they, acting in association with bacteria, can play the role of a trigger for the disease.

Risk factors

Risk factors for gestational pyelonephritis:

• history of urinary tract infection;
• malformations of the kidneys and urinary tract, stones in the kidneys and ureters;
• inflammatory diseases of the female genital organs;
• diabetes mellitus;
• urodynamic disorders caused by pregnancy (dilation and hypokinesia of the intracavitary system of the kidneys and ureters against the background of metabolic changes);
• low socioeconomic status.

Acute pyelonephritis of pregnancy occurs in 20–40% of women with untreated asymptomatic bacteriuria, which allows us to consider this phenomenon also as a risk factor for the development of gestational pyelonephritis.

Many women develop pyelonephritis in childhood, and the disease usually proceeds latently until the onset of the so-called “critical periods”:

• establishment of menstrual function;
• beginning of sexual activity;
• pregnancy.

This is primarily due to pronounced hormonal changes in the body. Pyelonephritis is more often diagnosed in primigravidas, which apparently depends on the insufficiency of adaptation mechanisms to the changes (immune, hormonal, etc.) that are inherent in the woman's body during the gestation process. Most women experience attacks of pyelonephritis in the second trimester of pregnancy (22–28 weeks).

The development of gestational pyelonephritis can lead to disruption of pregnancy, childbirth and the postpartum period. Thus, with pyelonephritis, pregnancy in 40-70% of cases can be complicated by gestosis, the frequency of premature births increases, fetal hypotrophy and chronic placental insufficiency develop.

Pathogenesis

Pregnancy predisposes women to an increased risk of developing pyelonephritis. High progesterone levels cause smooth muscle relaxation and decreased peristalsis of the renal collecting system. Decreased detrusor tone of the bladder results in incomplete emptying and increased bladder capacity. In addition, the pressure of the pregnant uterus on the renal system predisposes to varying degrees of dilation of the renal calyces, leading to urinary stasis and the formation of foci for bacterial colonization. This is further enhanced by the physiological changes during pregnancy associated with increased proteinuria and glucosuria, which promote the growth of microorganisms. [ 6 ]

Forms

There is no single classification of this disease. According to pathogenesis, the following forms of pyelonephritis are distinguished.

• Primary.
• Secondary:
  • obstructive, with anatomical anomalies;
  • in case of renal dysembryogenesis;
  • in dysmetabolic nephropathy.

Depending on the nature of the course, the following forms of pyelonephritis are distinguished.

• Spicy.
• Chronic:
  • manifest recurrent form;
  • latent form.

Depending on the period of the disease, the following forms are distinguished:

• exacerbation (active);
• reverse development of symptoms (partial remission);
• remission (clinical and laboratory).

Classification of pyelonephritis according to the preservation of renal function:

• without renal impairment;
• with impaired renal function.

Complications and consequences

The two most serious complications of pyelonephritis during pregnancy are sepsis and pulmonary insufficiency or ARDS, which occur in 1.9–17% and 0.5–7% of cases, respectively. [ 7 ], [ 8 ] Early recognition of these complications is critical to ensure a favorable outcome; therefore, it would be useful to immediately identify which patients with pyelonephritis are at higher risk for these potentially devastating complications. [ 9 ] Fever is the most common sign or symptom of sepsis during pregnancy; however, additional abnormal vital signs may be present, indicating a more advanced case of sepsis. [ 10 ]

Diagnostics gestational pyelonephritis

The diagnosis of gestational pyelonephritis is made if the pregnant woman has:

• characteristic clinical picture (acute febrile onset of the disease, dysuria, positive percussion symptom);
• leukocyturia more than 4000 in 1 ml;
• bacteriuria more than 10 ⁵ CFU/ml;
• leukocytosis more than 11×10 ⁹ /l, shift in blood count to the left.

The diagnosis of pyelonephritis is established clinically based on symptoms of fever, flank pain, and costovertebral angle tenderness, accompanied by pyuria or bacteriuria.

Physical examination in gestational pyelonephritis

Clinically, gestational pyelonephritis occurs in acute or chronic form. In case of exacerbation of chronic pyelonephritis, the disease should be considered as acute inflammation. The clinical picture of gestational pyelonephritis in different periods of pregnancy has its own typical features. They are caused mainly by the degree of violation of the passage of urine from the upper urinary tract. If in the first trimester of pregnancy there may be severe pain in the lumbar region with irradiation to the lower abdomen, external genitalia, resembling renal colic, then in the second and third trimesters the pain is less intense.

Acute pyelonephritis in pregnant women is characterized by symptoms of general intoxication of the body, fever with chills and profuse sweating, arthralgia and muscle pain, which is combined with complaints of pain in the lumbar region, often radiating to the upper abdomen, groin, and thigh. Discomfort during urination and dysuria are also noted. An objective examination reveals pain when pressing in the costovertebral angle on the affected side, and a positive percussion symptom. With simultaneous bimanual palpation of the lumbar and hypochondrium, local pain in the lumbar region and tension in the muscles of the anterior abdominal wall are noted.

In some patients, symptoms of general intoxication prevail over local manifestations, and therefore laboratory testing is necessary to clarify the diagnosis.

Chronic pyelonephritis during the gestational process can occur with exacerbations (clinical picture of acute pyelonephritis), as well as in the form of asymptomatic bacteriuria.

Laboratory and instrumental research methods for gestational pyelonephritis

• A clinical blood test showed leukocytosis over 11x10 ⁹ /l, a neutrophilic shift in the leukocyte formula to the left due to an increase in band neutrophils, hypochromic anemia (hemoglobin below 100 g/l), and an increase in ESR.
• Biochemical blood test. The level of total protein, cholesterol, residual nitrogen in pyelonephritis is usually normal; dysproteinemia (increased alpha2- and gamma-globulin levels), increased levels of sialic acids, mucoproteins, and a positive reaction to C-reactive protein are of diagnostic significance.
• Urine analysis. Pyuria is present in almost all patients with pyelonephritis, it is an early laboratory symptom. Leukocyturia is more than 4000 in 1 ml (Nechiporenko test). During microscopy of urinary sediment, cylindruria can be detected in parallel with leukocyturia, mainly due to hyaline or leukocyte cylinders (detection of the latter against the background of pyuria with a high degree of probability confirms the diagnosis of pyelonephritis), minor proteinuria, sometimes microhematuria. An alkaline reaction of urine is most often detected due to the vital activity of urea-producing bacteria.
• Reberg's test: the filtration function of the kidneys is impaired only in severe cases of the disease.
• Microbiological research.

The presence of a large amount of desquamated epithelium in urine smears indicates contamination of the urine with vaginal flora, and therefore the analysis must be repeated.

• The detection of 1 or more bacterial cells in the field of view of the microscope indicates the presence of 10 ⁵ or more microorganisms in 1 ml of urine.
• The standard method of microbiological research is urine culture with determination of the sensitivity of infectious agents to antibacterial drugs.

The diagnostic value of bacteriological examination of urine can be defined as high if the growth of the pathogen in an amount of ≥ 10 ⁵ CFU/ml is detected. A necessary condition for the reliability of the results of bacteriological examination is the correct collection of urine. Urine for bacteriological examination is collected after thorough toilet of the external genitalia, excluding the presence of vaginal discharge in the urine. The middle portion of urine is collected in a sterile container with a lid in the amount of 10-15 ml. Urine for microbiological examination should be collected before the start of antibacterial therapy. If the patient is receiving antibacterial drugs, they should be discontinued 2-3 days before the examination. The results of bacterioscopy and urine culture must be interpreted taking into account clinical data. In the urine of 10% of patients with urinary tract infections, two microorganisms may be present, each of which can be considered the main causative agent of the disease. If more than two types of microorganisms are detected, the results are assessed as suspected contamination and require repeat testing.

• In 10–20% of patients with pyelonephritis, the infectious agent is isolated from the blood. The microorganism found in the blood is usually similar to that found in the urine.
• Ultrasound scanning of the kidneys is an auxiliary method of examination. Indirect signs of acute pyelonephritis are an increase in the size of the kidney, a decrease in the echogenicity of the parenchyma as a result of edema. Ultrasound of the kidneys in chronic pyelonephritis is uninformative.

Differential diagnosis

Differential diagnostics must be carried out with the following diseases and pathological conditions:

• appendicitis;
• acute cholecystitis;
• renal colic against the background of urolithiasis;
• ectopic pregnancy;
• ruptured ovarian cyst;
• respiratory tract infections (with fever);
• toxoplasmosis.

Treatment gestational pyelonephritis

Optimal antimicrobial agents for empirical therapy in the first trimester of pregnancy based on in vitro and in vivo studies are inhibitor-protected aminopenicillins. The use of inhibitor-protected penicillins allows overcoming the resistance of enterobacteria producing chromosomal beta-lactamases of a wide and extended spectrum, as well as staphylococci producing plasmid beta-lactamases of class A.

In the second trimester, inhibitor-protected penicillins and cephalosporins are considered as empirical therapy.

Aminopenicillins are not recommended as drugs of choice for this pathology due to proven global and high regional resistance rates.

When choosing doses of antibacterial drugs, it is necessary to consider their safety for the fetus: fluoroquinolones cannot be used throughout pregnancy; sulfonamides are contraindicated in the first and third trimesters, aminoglycosides are used only for vital indications.

The proven teratogenicity of tetracyclines, selective sensitivity of lincosamides, rifampicin, glycopeptides (not effective against gram-negative bacteria) exclude these antimicrobial agents from the list of drugs of choice.

The total functional capacity of the kidneys should also be taken into account. In case of hyposthenuria and decreased creatinine clearance, the doses of drugs should be reduced by 2-4 times to avoid accumulation and development of adverse reactions. At first, the drugs are administered parenterally, then switched to oral administration. The duration of therapy is at least 14 days. In the absence of positive clinical and laboratory dynamics of the disease against the background of empirical therapy for 3-4 days, it is necessary to conduct a microbiological study of urine and correct the therapy based on the results of determining the resistance of the isolated microorganism.

Antibacterial therapy carried out in different trimesters of pregnancy and the postpartum period

In the first trimester of pregnancy, preference should be given to natural and semi-synthetic penicillins due to the possible harmful effect of drugs of other groups on the fetus during its organogenesis. Due to the high resistance of uropathogenic strains of E. coli to natural penicillins, the use of aminopenicillins with beta-lactamase inhibitors is recommended.

In the II and III trimesters of pregnancy, in addition to drugs, it is possible to use II and III generation cephalosporins, aminoglycosides, and macrolides. I generation cephalosporins (cefazolin, cephalexin, and cephradine) have weak activity against E. coli.

In the postpartum period, carbapenems, fluoroquinolones, co-trimoxazole, nitrofurans, monobactams are used; however, during the period of antibacterial therapy, it is necessary to temporarily stop breastfeeding.

Although 10–14 days of therapy is accepted for the treatment of pyelonephritis,[ 11 ] particularly in pregnant women, new studies have called into question the duration of therapy.[ 12 ] Treatment options for pyelonephritis in pregnant women are limited. Antimicrobial resistance is increasing at an alarming rate, with few new treatment options for Gram-negative bacteria in non-pregnant and pregnant women.[ 13 ] The rise of extended-spectrum β-lactamase (ESBL)-producing bacteria is compounding the problem, as antimicrobials such as cephalosporins, which have a good safety profile in pregnant women, are ineffective. Antimicrobial efficacy has been assessed in only four randomized controlled trials in pregnant women, involving a total of 90,[ 14 ] 178,[ 15 ] 179,[ 16 ] and 101,[ 17 ] or 548 women. These studies concluded that in patients without bacteremia, oral cephalexin (500 mg every 6 hours) was no different in efficacy or safety than intravenous (IV) cephalothin (1 g every 6 hours); once-daily IV ceftriaxone was as effective as multiple daily doses of cefazolin. No difference in clinical response was observed with intravenous ampicillin and gentamicin, intravenous cefazolin, or intramuscular ceftriaxone, whereas cefuroxime (750 mg every 8 hours intravenously) was more effective and better tolerated than cefradine (1 g every 6 hours intravenously). A review article reported that 2 weeks of therapy seem to be acceptable for the treatment of acute pyelonephritis in women, and not particularly in pregnant women;[ 18 ] however, courses of 10 to 14 days are recommended.[ 19 ],[ 20 ]

Along with antibacterial therapy, infusion, detoxification, sedative, desensitizing, metabolic therapy, herbal and saluretic diuretics are necessary. Careful monitoring of the fetus is necessary, prevention of hypoxia and fetal malnutrition is mandatory. If fetal growth retardation is detected, appropriate treatment is carried out. In severe cases, with the development of purulent pyelonephritis and the clinical picture of urosepsis against the background of the acuteness of the infectious process (especially complicated by acute renal failure), therapy for disseminated intravascular coagulation syndrome is carried out: anticoagulants - sodium heparin subcutaneously at a dose of 10,000 U / day, low molecular weight heparins, disaggregants (pentoxifylline, ticlopidine), transfusions (jet at the rate of 10 ml / kg of the patient's weight) of fresh frozen plasma. The latter is necessary when signs of hemorrhagic syndrome appear, acute renal failure develops, and severe intoxication occurs. If conservative therapy is unsuccessful, surgical treatment is indicated (nephrostomy, kidney decapsulation, nephrectomy).

Indications for consultation with other specialists

Urologist:

• impaired passage of urine (ureteral catheterization);
• in the development of purulent-destructive inflammation - apostematous nephritis, carbuncle and kidney abscess - for surgical treatment.

Prevention

Prevention of gestational pyelonephritis is aimed at early detection of asymptomatic bacteriuria, urodynamic disorders, and initial signs of the disease.

Antibacterial therapy for asymptomatic bacteriuria in pregnant women significantly reduces the likelihood of developing pyelonephritis.

Since asymptomatic bacteriuria and gestational pyelonephritis are associated with a high risk of preterm labor and premature rupture of membranes, patients with a history of these conditions should undergo monthly microbiological testing of urine and appropriate treatment.

The effectiveness of herbal medicine in preventing pyelonephritis in pregnant women has not been reliably confirmed.

Forecast

The criterion for recovery is the absence of leukocyturia in a three-fold urine test. Subsequently, laboratory parameters are monitored once every 2 weeks.

In case of frequent exacerbations of pyelonephritis outside pregnancy, the generally accepted approach is to prescribe monthly prophylactic courses (1–2 weeks) of antibacterial drugs. However, at present there is no reliable data indicating the effectiveness and appropriateness of prophylactic courses of antibacterial drugs in pyelonephritis. In addition, the prophylactic use of antibiotics contributes to the selection of resistant strains of microorganisms, which allows us to recognize the prophylactic use of antibiotics in pregnant women as unjustified.

More justified are non-drug measures to prevent exacerbations of pyelonephritis, which include an adequate drinking regimen - 1.2-1.5 liters, positional therapy (knee-elbow position to improve urine flow), and the use of herbal medicine.