Role of dexamethasone in controlling the proinflammatory cytokine cascade in the first episode of paediatric acute pyelonephritis.

AIM: Febrile urinary tract infection is a common bacterial infection in childhood. The kidney damage after acute pyelonephritis (APN) could be related to the stimulation of the proinflammatory response. We aimed to investigate the role of inflammatory cytokines and the effect of dexamethasone after a first episode of APN. METHODS: Subanalysis of the DEXCAR RCT in which children with confirmed APN (1 month-14 years) were randomly assigned to receive a 3 days course of either intravenous dexamethasone or placebo. Urinary cytokine levels at diagnosis and after 72 h of treatment were measured. RESULTS: Ninety-two patients were recruited. Younger patients, males and those with abnormalities in the ultrasound study or vesicoureteral reflux showed higher values of urinary cytokines. Patients with severe APN had higher Tumour Necrosis Factor (TNF)α levels (81.0 ± 75.8 vs. 33.6 ± 48.5 pg/mg creatinine, p = 0.015). Both intervention groups showed similar basal clinical characteristics, including urinary cytokine levels. Treatment reduced urinary cytokine levels irrespective of dexamethasone administration. Neither the intervention group nor the urinary cytokine levels modulated the development of kidney scars. CONCLUSION: Basal urinary cytokines were associated with age, abnormal ultrasound and vesicoureteral reflux. Patients with severe APN had higher TNFa urinary levels. Administration of dexamethasone in children with APN does not improve the control of the proinflammatory cytokine cascade.

Prospective Phycocompounds for Developing Therapeutics for Urinary Tract Infection.

Antibiotic resistance of bacteria is causing clinical and public health concerns that are challenging to treat. Infections are becoming more common in the present era, and patients admitted to hospitals often have drug-resistant bacteria that can spread nosocomial infections. Urinary tract infections (UTIs) are among the most common infectious diseases affecting all age groups. There has been an increase in the proportion of bacteria that are resistant to multiple drugs. Herein is a comprehensive update on UTI-associated diseases: cystitis, urethritis, acute urethral syndrome, pyelonephritis, and recurrent UTIs. Further emphasis on the global statistical incidence and recent advancement of the role of natural products in treating notorious infections are described. This updated compendium will inspire the development of novel phycocompounds as the prospective antibacterial candidate.

Particularities of Urinary Tract Infections in Diabetic Patients: A Concise Review.

Diabetes mellitus is a chronic disease that, untreated or poorly controlled, can lead to serious complications, reducing life expectancy and quality. Diabetic patients are more likely to develop infections, including many common infections, but also pathognomonic ones such as emphysematous pyelonephritis, malignant otitis externa, mucormycosis and Fournier's gangrene. Considering the fact that diabetic patients experience more frequently urinary tract infections (UTIs) with a worse prognosis than non-diabetic people, we conducted a review study based on data in the literature, following the particularities of UTIs in this group of patients, the risk factors, the mechanisms involved and the challenges in their management. The findings highlight that UTI in diabetic patients have some particularities, including a more frequent evolution to bacteremia, increased hospitalizations, and elevated rates of recurrence and mortality than non-diabetic patients. The possible risk factors identified seem to be female gender, pregnancy, older age, UTI in the previous six months, poor glycemic control and duration of diabetes. The mechanisms involved are related to glucosuria and bladder dysfunction, factors related to bacterial strains and host response. The bacterial strains involved in UTIs in diabetic patients and their antibiotic susceptibility profile are, with some exceptions, similar to those in non-diabetic people; however, the antimicrobial agents should be carefully chosen and the duration of the treatment should be as those required for a complicated UTI. The data related to the risk of developing UTIs in patients treated with SGLT-2 inhibitors, a new class of oral hypoglycaemic agents with cardiovascular and renal benefits, are controversial; overall, it was evidenced that UTIs occurred at the initiation of the treatment, recurrent infection was uncommon and the majority of UTIs responded to treatment with standard antibiotics. Moreover, interruption or discontinuation of SGLT-2 inhibitor as a result of UTI was rare and SGLT-2 inhibitors did not increase the risk of severe infections such as urosepsis and pyelonephritis.

Szechwan Lovage Rhizome Extract Improves Renal Function and Alleviates Inflammatory Responses in Pyelonephritis Rats Infected with Escherichia Coli via IL-6/STAT3 Axis.

The objective of this study was to probe the effect and mechanism of Szechwan Lovage Rhizome (Chuanxiong, CX) extract on renal function (RF) and inflammatory responses (IRs) in acute pyelonephritis (APN) rats infected with Escherichia coli (E. coli). Fifteen SD rats were randomized to intervention, model and control groups. Rats in the control were fed normally without treatment, rats in the APN model were infected with E. coli, and rats in the intervention group were intragastrically administered CX extract after infection with E. coli. HE staining detected pathological changes in the kidney tissues in rats. Levels of renal function indexes and inflammatory factors (IFs) were measured by ELISA and an automatic biochemical analyzer. Besides, levels of IL-6/signal transducer and activator of transcription 3 (STAT3) pathway-related genes in rat kidney tissue were detected by qRT-PCR and western blot. the experimental results showed that IL-1ß, IL-8, TNF-α and RF levels were the highest in the model group and the lowest in the control group, with those of the intervention group in between (P<0.05). Besides, the IL-6/STAT3 axis was markedly activated in the model group but inhibited in the intervention group (P<0.05). Subsequently, activated IL-6/STAT3 signal promoted IFs (IL-1ß, IL-8 and TNF-α) and RF (BUN, Scr, ß2-MG and UA), but this effect was offset after CX treatment (P<0.05). In conclusion, CX extract could improve RF and inhibit IRs of APN rats infected with E. coli by inhibiting the IL-6/STAT3 axis, which may be a new choice for APN treatment in the future.

Isolated renal mucormycosis masquerading as emphysematous pyelonephritis.

Mucormycosis is an acute, life-threatening infection and isolated renal involvement is rare. Due to the angioinvasive nature of the disease, it is rapidly progressive and can be lethal if not managed expeditiously. In patients with underlying conditions of immunosuppression, diabetes mellitus, transplantation, COVID-19, intravenous drug and substance use and pyelonephritis, which is unable to be controlled via regular antibiotics, mucormycosis must be considered on the differential and antifungals must be empirically started. Most cases are often diagnosed on histopathology, which causes delayed treatment and resolution. We present a case of emphysematous pyelonephritis diagnosed on imaging and was later found to have mucormycosis on histopathological examination.

Biopsy-proven fungal pyelonephritis complicating delayed graft function in a renal transplant patient.

Delayed graft function (DGF) is a common phenomenon following renal transplantation, which can be due to several factors. A rare cause includes invasive fungal infections, which can often be a challenge to diagnose. Nonetheless, prompt identification of such infections particularly within transplant patients is essential as they can lead to severe downstream sequelae, including graft loss and even death. We describe here a challenging case of fungal pyelonephritis complicating and potentially leading to DGF and further dialysis dependence within a renal transplant patient. Notably, we highlight the importance and clinical utility of biopsy to confirm the diagnosis, as investigations may be largely normal otherwise. Furthermore, we emphasise that with early identification of these infections, effective antifungal treatment can be commenced in a timely fashion leading to better patient outcomes and good graft function.

Antibiotic prophylaxis for percutaneous renal biopsy: study protocol for a prospective randomized trial.

BACKGROUND: The major complication of renal biopsy is bleeding. Infection is an extremely rare complication of percutaneous renal biopsy, providing sterile techniques are used and bowel perforation does not occur. However, the questionnaire included in the Kidney Biopsy Guidebook 2020 in Japan reported that antibiotic prophylaxis was administered to patients undergoing percutaneous renal biopsy at 61% of 170 adult institutions and 57% of 54 pediatric institutions. The objective of this study is to show the non-inferiority of not administering antibiotic prophylaxis for percutaneous renal biopsy. METHODS: Patients aged ≥15 years who are scheduled to undergo percutaneous renal biopsy are eligible for inclusion in the study. Three hundred and sixty-four patients will be recruited at 6 hospitals. The patients will be randomly assigned at a 1:1 ratio to receive either a single dose of intravenous cefazolin (1 g) or no antibiotic prophylaxis. The primary outcome is the number of patients that exhibit positive urine cultures (>105 colony-forming units/ml) 3 or 4 days after the renal biopsy, or at which point the patients are diagnosed with pyelonephritis until 3 or 4 days after the renal biopsy. The secondary outcomes are the number of patients who are diagnosed with pyelonephritis within 30 days after the renal biopsy, the number of patients who are diagnosed with puncture site infections within 30 days after the renal biopsy, the number of patients who are diagnosed with an infection other than pyelonephritis or a puncture site infection within 30 days after the renal biopsy, and the number of patients who experience cefazolin-induced side effects. DISCUSSION: This randomized controlled trial aims to show the non-inferiority of not administering antibiotic prophylaxis for percutaneous renal biopsy. If this study shows that antibiotic prophylaxis is not needed, it would help to ensure patient safety and prevent the development of antibiotic-resistant bacteria. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000042378 . Registered on 7 Nov 2020.

Reducing antibiotic use in uncomplicated urinary tract infections in adult women: a systematic review and individual participant data meta-analysis.

BACKGROUND: Randomised controlled trials (RCTs) investigated analgesics, herbal formulations, delayed prescription of antibiotics, and placebo to prevent overprescription of antibiotics in women with uncomplicated urinary tract infections (uUTI). OBJECTIVES: To estimate the effect of these strategies and to identify symptoms, signs, or other factors that indicate a benefit from these strategies. DATA SOURCES: MEDLINE, EMBASE, Web of Science, LILACS, Cochrane Database of Systematic Reviews and of Controlled Trials, and ClinicalTrials. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: RCTs investigating any strategies to reduce antibiotics vs. immediate antibiotics in adult women with uUTI in primary care. METHODS: We extracted individual participant data (IPD) if available, otherwise aggregate data (AD). Bayesian random-effects meta-analysis of the AD was used for pairwise comparisons. Candidate moderators and prognostic indicators of treatment effects were investigated using generalised linear mixed models based on IPD. RESULTS: We analysed IPD of 3524 patients from eight RCTs and AD of 78 patients. Non-antibiotic strategies increased the rates of incomplete recovery (OR 3.0; 95% credible interval (CrI), 1.7-5.5; Bayesian p-value (pB) = 0.0017; τ = 0.6), subsequent antibiotic treatment (OR 3.5; 95% CrI, 2.1-5.8; pB = 0.0003) and pyelonephritis (OR 5.6; 95% CrI, 2.3-13.9; pB = 0.0003). Conversely, they decreased overall antibiotic use by 63%. Patients positive for urinary erythrocytes and urine culture were at increased risk for incomplete recovery (OR 4.7; 95% CrI, 2.1-10.8; pB = 0.0010), but no difference was apparent where both were negative (OR 0.8; 95% CrI, 0.3-2.0; pB = 0.667). In patients treated using non-antibiotic strategies, urinary erythrocytes and positive urine culture were independent prognostic indicators for subsequent antibiotic treatment and pyelonephritis. CONCLUSIONS: Compared to immediate antibiotics, non-antibiotic strategies reduce overall antibiotic use but result in poorer clinical outcomes. The presence of erythrocytes and tests to confirm bacteria in urine could be used to target antibiotic prescribing.

Incidence rates and trends of childhood urinary tract infections and antibiotic prescribing: registry-based study in general practices (2000 to 2020).

BACKGROUND: To improve the management of childhood urinary tract infections, it is essential to understand the incidence rates, testing and treatment strategy. METHODS: A retrospective study using data from 45 to 104 general practices (2000 to 2020) in Flanders (Belgium). We calculated the incidence rates (per 1000 person-years) of cystitis, pyelonephritis, and lab-based urine tests per age (< 2, 2-4, 5-9 and 10-18 years)) and gender in children and performed an autoregressive time-series analysis and seasonality analysis. In children with UTI, we calculated the number of lab-based urine tests and antibiotic prescriptions per person-year and performed an autoregressive time-series analysis. RESULTS: There was a statistically significant increase in the number of UTI episodes from 2000 to 2020 in each age group (p < 0.05), except in boys 2-4 years. Overall, the change in incidence rate was low. In 2020, the incidence rates of cystitis were highest in girls 2-4 years old (40.3 /1000 person-years 95%CI 34.5-46.7) and lowest in boys 10-18 (2.6 /1000 person-years 95%CI 1.8-3.6) The incidence rates of pyelonephritis were highest in girls 2-4 years (5.5, 95%CI 3.5-8.1 /1000 person-years) and children < 2 years of age (boys: 5.4, 95%CI 3.1-8.8 and girls: 4.9, 95%CI 2.7-8.8 /1000 person-years). In children 2-10 years, there was an increase in number of lab-based urine tests per cystitis episode per year and a decrease in total number of electronic antibiotic prescriptions per cystitis episode per year, from 2000 to 2020. In children with cystitis < 10 years in 2020, 51% (95%CI 47-56%) received an electronic antibiotic prescription, of which the majority were broad-spectrum agents. CONCLUSIONS: Over the last 21 years, there was a slight increase in the number of UTI episodes diagnosed in children in Flemish general practices, although the overall change was low. More targeted antibiotic therapy for cystitis in accordance with clinical guidelines is necessary to reduce the use of broad-spectrum agents in children below 10 years.

Immunomodulation therapy offers new molecular strategies to treat UTI.

Innovative solutions are needed for the treatment of bacterial infections, and a range of antibacterial molecules have been explored as alternatives to antibiotics. A different approach is to investigate the immune system of the host for new ways of making the antibacterial defence more efficient. However, the immune system has a dual role as protector and cause of disease: in addition to being protective, increasing evidence shows that innate immune responses can become excessive and cause acute symptoms and tissue pathology during infection. This role of innate immunity in disease suggests that the immune system should be targeted therapeutically, to inhibit over-reactivity. The ultimate goal is to develop therapies that selectively attenuate destructive immune response cascades, while augmenting the protective antimicrobial defence but such treatment options have remained underexplored, owing to the molecular proximity of the protective and destructive effects of the immune response. The concept of innate immunomodulation therapy has been developed successfully in urinary tract infections, based on detailed studies of innate immune activation and disease pathogenesis. Effective, disease-specific, immunomodulatory strategies have been developed by targeting specific immune response regulators including key transcription factors. In acute pyelonephritis, targeting interferon regulatory factor 7 using small interfering RNA or treatment with antimicrobial peptide cathelicidin was protective and, in acute cystitis, targeting overactive effector molecules such as IL-1ß, MMP7, COX2, cAMP and the pain-sensing receptor NK1R has been successful in vivo. Furthermore, other UTI treatment strategies, such as inhibiting bacterial adhesion and vaccination, have also shown promise.

Acute Allograft Pyelonephritis: Vague Symptoms, Indeterminate Laboratory Results, and the Necessity of Indication Biopsy.

OBJECTIVES: In this study, we examined the clinical and biochemical features of biopsy-proven acute pyelonephritis among 769 kidney transplant recipients. MATERIALS AND METHODS: This cohort study was performed between January 2003 and December 2019 at the University of Health Sciences (Izmir, Turkey). Acute pyelonephritis refers to urinary tract infection with acute graft dysfunction. All patients with suspected acute pyelonephritis underwent diagnostic biopsy and received antibiotic treatment for an average of 14 to 21 days. Patients with acute pyelonephritis (18/769, 2.3%) were categorized into groups of 9 patients each: group 1 developed acute pyelonephritis in the first 6 months, and group 2 developed acute pyelonephritis >6 months posttransplant. RESULTS: All patients in group 1 had acute graft dysfunction; only 2 (22%) were symptomatic. All patients recovered baseline graft function after treatment. Patients in group 2 had at least 2 laboratory findings that included leukocytosis, neutrophilia, and high C-reactive protein values. Six patients had urine culture positivity. Recurrent pyelonephritis occurred in 3 patients. Four patients had graft loss. Over the mean follow-up of 48.0 ± 28.4 months, 14 patients (78%) were alive with a functioning graft. CONCLUSIONS: Diagnostic biopsy is of great importance in patients with urinary tract infection accompanied by acute graft dysfunction in the first 6 months after transplant.

Comparing outcomes among outpatients treated for pyelonephritis with oral cephalosporins versus first-line agents.

Fluoroquinolones and trimethoprim/sulfamethoxazole (TMP-SMX) are first-line agents for acute pyelonephritis. Oral ß-lactams are second-line agents owing to reported lower efficacy rates, primarily seen with aminopenicillins rather than cephalosporins. The increase in resistance rates and adverse effects associated with first-line agents provides justification to reconsider oral cephalosporins for pyelonephritis. Therefore, the objective of this study was to determine whether there is a difference in urinary tract infection (UTI) recurrence rates between oral cephalosporins and first-line agents in the treatment of acute pyelonephritis. This was a retrospective, single-centre, observational cohort study from 1 December 2018 to 31 May 2020. The study population was adult TRICARE beneficiaries with a diagnosis of acute pyelonephritis who were treated with oral antibiotics. The two cohorts compared were first-line antibiotics (ciprofloxacin, levofloxacin and TMP-SMX) and oral cephalosporins. The primary outcome was UTI recurrence rate at 30 days, which was defined as a repeat clinic visit, emergency department visit or hospital admission for a UTI (cystitis or pyelonephritis). The secondary outcome was to determine independent risk factors for UTI recurrence. A total of 268 cephalosporin and 211 first-line cases were included. The primary composite outcome of UTI recurrence within 30 days occurred in 44 (16%) cephalosporin and 36 (17%) first-line cases (P = 0.851). Independent risk factors for UTI recurrence were chronic kidney disease and Klebsiella spp. isolation. In conclusion, there was no significant difference in UTI recurrence rates between oral cephalosporins and first-line agents in the treatment of acute pyelonephritis in the outpatient setting.

Antimicrobial Treatment Options for Difficult-to-Treat Resistant Gram-Negative Bacteria Causing Cystitis, Pyelonephritis, and Prostatitis: A Narrative Review.

Urinary tract infections, including cystitis, acute pyelonephritis, and prostatitis, are among the most common diagnoses prompting antibiotic prescribing. The rise in antimicrobial resistance over the past decades has led to the increasing challenge of urinary tract infections because of multidrug-resistant and "difficult-to-treat resistance" among Gram-negative bacteria. Recent advances in pharmacotherapy and medical microbiology are modernizing how these urinary tract infections are treated. Advances in pharmacotherapy have included not only the development and approval of novel antibiotics, such as ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, ceftolozane/tazobactam, cefiderocol, plazomicin, and glycylcyclines, but also the re-examination of the potential role of legacy antibiotics, including older aminoglycosides and tetracyclines. Recent advances in medical microbiology allow phenotypic and molecular mechanism of resistance testing, and thus antibiotic prescribing can be tailored to the mechanism of resistance in the infecting pathogen. Here, we provide a narrative review on the clinical and pre-clinical studies of drugs that can be used for difficult-to-treat resistant Gram-negative bacteria, with a particular focus on data relevant to the urinary tract. We also offer a pragmatic framework for antibiotic selection when encountering urinary tract infections due to difficult-to-treat resistant Gram-negative bacteria based on the organism and its mechanism of resistance.

Facklamia hominis pyelonephritis in a pediatric patient: first case report and review of the literature.

BACKGROUND: Pyelonephritis is one of the most serious bacterial illnesses during childhood. Gram-negative organisms account for up to 90% of the cases. Gram-positive bacteria are uncommon causes of urinary tract infections, and only a few cases caused by Facklamia hominis have been reported in the literature. CASE PRESENTATION: A five-year-old girl with tracheostomy and gastrostomy and past medical history of congenital lymphangioma presented with a two-week history of with intermittent fever, frequent urination, and vesical tenesmus. Diagnosis of pyelonephritis was made. Urine culture reported colonies with alpha-hemolysis in blood agar at 48-h of incubation and Facklamia hominis was identified by MALDI-TOF. The patient was successfully treated with gentamicin. CONCLUSIONS: This is the first reported case of pyelonephritis by Facklamia hominis in a child, and the second involving infection in a pediatric patient. Although this pathogen is uncommon, current treatment of F. hominis is a challenge for physicians. This case illustrates the requirement to standardize identification and treatment of care to avoid treatment failure and antimicrobial resistance.

Emphysematous cystitis with bilateral pyelonephritis in a pediatric patient with COVID-19.

A 15-year-old female adolescent with a medical history of recurrent urinary tract infections and grade 1 left-sided vesicoureteral reflux presented to the emergency room with abdominal and back pain. Labs revealed a haemoglobin A1c (HbA1c) of 9.1% and a random blood glucose of 200 mg/dL, consistent with new-onset diabetes mellitus. Nasopharyngeal COVID-19 PCR test returned positive. A CT scan of the abdomen and pelvis revealed bilateral attenuation of the kidneys and air in the bladder, which was confirmed by pelvic ultrasound. Gas subsequently resolved 2 days later after treatment with antibiotics, and a diagnosis of emphysematous cystitis was made. Emphysematous cystitis in the paediatric population is an extremely rare condition with four cases reported in the literature. Furthermore, there has been a reported association between COVID-19, cystitis and non-typical course of urinary symptoms. Local inflammation obstructing transportation of formed gas is one of the proposed mechanisms underlying emphysematous cystitis, and so COVID-19 may be yet another predisposing factor.

Bad bugs: antibiotic-resistant bacteriuria in pregnancy and risk of pyelonephritis.

BACKGROUND: The introduction of antibiotics has significantly reduced morbidity and mortality from microbial infections, but the rise of antibiotic-resistant and multidrug-resistant microbes is of increasing clinical concern. Few studies have examined the prevalence and impact of antibiotic resistance in common antenatal infections. OBJECTIVE: This study aimed to determine whether pregnant women with a urine culture positive for antibiotic-resistant or multidrug-resistant gram-negative bacteria are at increased risk of developing pyelonephritis than pregnant women infected with antibiotic-susceptible organisms. STUDY DESIGN: This was a retrospective cohort study of pregnant women with asymptomatic bacteriuria or acute cystitis from a single health system from July 2013 to May 2019. Women with gram-negative antibiotic-resistant (resistance to 1-2 antibiotic classes) and multidrug-resistant (resistance to ≥3 antibiotic classes) lower urinary tract infections were compared with women with antibiotic-susceptible urinary tract infections in terms of demographic, infectious, antepartum, and intrapartum data. The primary outcome was pyelonephritis, defined as a billing code for pyelonephritis plus fever or flank pain. The secondary outcomes were length of stay in the hospital because of pyelonephritis, a composite of pyelonephritis complications (renal abscess, sepsis, and intensive care unit admission), and preterm delivery. The differences in the primary outcome were analyzed using multivariate logistic regression. RESULTS: A total of 573 women were eligible for inclusion. Of the 573 women, 334 (58%) had gram-negative bacteria on urine culture. Of the 334 cases, 173 (52%) were antibiotic susceptible, 74 (22%) were antibiotic resistant, and 87 (26%) were multidrug resistant. Women with antibiotic-resistant and multidrug-resistant infections were more likely to have hypertension (P=.004), to be Black (P=.03), to have public insurance (P=.002), and to experience more urinary infections (P=.001). Pyelonephritis was more common in women with antibiotic-resistant (adjusted odds ratio, 2.27; 95% confidence interval, 1.08-4.78) and multidrug-resistant (adjusted odds ratio, 3.06; 95% confidence interval, 1.57-5.96) infections than in women with antibiotic-susceptible urinary tract infections. Length of stay, preterm delivery, and pyelonephritis complications did not differ between antibiotic-susceptible and antibiotic-resistant and multidrug-resistant infections. CONCLUSION: In an age of increasing antibiotic resistance, more than one-half of pregnant women with bacteriuria experience at least 1 infection with an antibiotic-resistant organism. These resistance patterns have a real clinical impact as pregnant women with antibiotic-resistant gram-negative lower urinary tract infections have an estimated 2- to 3-fold increased odds of developing pyelonephritis.

Rotula aquatica Lour. mitigates oxidative stress and inflammation in acute pyelonephritic rats.

The current study evaluates the efficacy of methanolic extract of Rotula aquatica Lour. (MERA) against inflammatory changes associated with acute pyelonephritis. The antioxidant enzymes such as SOD, CAT, GPx, GR and oxidative stress markers like GSH content, malondialdehyde (MDA) level, nitrate level, reactive oxygen species (ROS) level and renal toxicity markers were evaluated in this study. The mRNA level expression of Toll-like receptor 4 (TLR-4), nuclear transcription factor kappa B (NF-κB), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and Tamm Horsfall protein (THP) were studied by RT-PCR analysis. The oral administration of MERA increases the antioxidant enzyme status in pyelonephritis rat. The elevated levels of oxidative stress markers in pyelonephritic rats were ameliorated by the administration of MERA at 100 mg/kg and 200 mg/kg bwt of the rat. The mRNA level expression of major genes were restored to normal level by MERA.

[Clinical and pathogenetic aspects of the treatment and prevention of pyelonephritis in children].

INTRODUCTION: Treatment of pyelonephritis in children should be combined, long-term and individual-based. The success of the therapy in children largely depends on the prompt appointment and the correct choice of antimicrobial therapy. AIM: To evaluate the efficiency of the dietary supplement "Cystenium II" in a group of children aged 7 to 14 years with a diagnosis of acute and chronic recurrent pyelonephritis in the acute phase. MATERIALS AND METHODS: A total of 60 children aged 7 to 14 years with a diagnosis of acute or chronic recurrent pyelonephritis in the acute stage were included in the study. The clinical group consisted of 30 patients (mean age 12.1+/-1.8 years), while the control group included 30 patients of mean age 11.2+/-1.7 years. In the control group patients received only standard antibiotic therapy, while in the clinical group it was combined with a dietary supplement "Cystenium II" 1 tablet 2 times a day with meals for 14 days. After the course of antibacterial treatment, the children in the clinical group continued to take the studied dietary supplement for another 14 days in order to prevent the recurrence of pyelonephritis. The results of treatment (patient's condition, presence of pain, dysuria, fever) were assessed on the 3rd, 7th, 14th day, 1 and 6 months after the start of treatment. A urinalysis was performed at the baseline, on the 7th and 14th days, as well as after 1 and 6 months. Urine culture was performed before and after antibiotic therapy at the baseline, on the 14th day, 1 and 6 months after the start of treatment. RESULTS: The main indicators of urinalysis (leukocytes, red blood cells, protein) returned to normal values in 26 (86.7%) patients of the clinical group and in 23 (76.7%) patients of the control group on the 7th day after the start of treatment. At the completion of the basic therapy (after 14 days) normal clinical parameters (absence of leukocyturia, microhematuria, proteinuria) were observed in all patients of the clinical group and in 28 (93.3%) patients of the control group. After a month of follow-up, the disturbances in urinalysis (leukocytes, red blood cells, protein) in the control group were again seen in 3 (10%) patients, as well as after 6 months. However, in the clinical group all patients had normal urinalysis (absence of leukocyturia, microhematuria, proteinuria) after 1 month and only in 1 (3.3%) case leukocyturia, as well as an increase in the number of red blood cells and protein was detected by 6 months. DISCUSSION: According to our results, the use of dietary supplements "Cystenium II" (manufactured by Akvion, Russia), due to the constituents of D-mannose (450 mg), cranberry fruit extract with a standardized activity of 500 mg (36 mg of proanthocyanidins) and vitamin C (60 mg), may cause anti-inflammatory and anti-adhesive effects (resolving of leukocyturia and bacteriuria). This allows to use the dietary supplement Cystenium II in children from 7 years of age in the combination therapy of acute pyelonephritis, as well as exacerbation of chronic pyelonephritis. The obtained results showed a high overall therapeutic efficacy of combination therapy using Cystenium II after 6 months from the start of treatment (relapse in 1 patient), in contrast to the control group (relapse in 6 patients). CONCLUSIONS: the use of dietary supplement "Cystenium II" allowed to reduce the number of repeated courses of antibiotic therapy in children during 6 months of follow-up and, most likely, reduced the frequency of development of chronic pyelonephritis after an acute inflammation. Therefore, the wide clinical use of dietary supplements "Cystenium II" for the combined treatment of acute and exacerbation of chronic pyelonephritis in children older than 7 years seems to be very reasonable.

Nonasthmatic Churg-Strauss syndrome superimposed on chronic pyelonephritis: a case report.

Churg-Strauss syndrome (CSS) is a granulomatous small-vessel vasculitis. Asthma is seen in the majority of patients with CSS, but atypical nonasthmatic forms of CSS are also being recognized. We herein describe a 67-year-old woman with a history of chronic pyelonephritis and drug allergy reactions who was admitted to our hospital because of worsening renal function preceded by fever, purpura, sinusitis, and a positive urine culture that confirmed a urinary infection. She was initially treated with pipemidic acid for 7 days, followed by clarithromycin for sinusitis. Laboratory tests on admission showed an absolute eosinophil count of 1750 cells/µL and serum creatinine concentration of 4.72 mg/dL. Urine and blood cultures showed no growth. Kidney biopsy revealed crescent formations with diffuse interstitial fibrosis and foci of eosinophil infiltration. An atypical form of CSS was diagnosed based on tissue eosinophilia, peripheral eosinophilia, and sinusitis. Intravenous methylprednisolone and cyclophosphamide pulse therapy together with hemodialysis treatment improved the patient's clinical condition but did not resolve the kidney damage. The onset of an atypical form of CSS in our patient manifested as symptoms and signs mimicking those of chronic pyelonephritis and drug allergy reactions. The patient's chronic kidney disease finally progressed to dialysis dependence.