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Introduction: Urinary tract infections (UTI) are caused in 95% of cases by bacteria--E. coli. UTIs usually are limited to the lower urinary tract, but it may also evolve into pyelonephritis and acute kidney injury., Objectives: The aim of this study was the laboratory evaluation of renal function in an experimental model of ascending pyelonephritis caused by intravesical infusion of E. coli., Material & Methods: In female Wistar rats UTI was induced by intravesical administration of E. coli suspension in a dose 10(5) c.f.u./ml (Group 1), and 10(7) c.f.u./ml (Group 2). On the 0,7th, 14th and 21st day of the experiment the animals underwent the procedures of collecting blood and urine samples., Results: The results shown that in group 2 on the 7th and 14th day of the study the creatinine clearance decreased by 36%, and on 21th by 34%. The increase in serum uric acid concentration (micromol/l) in group 2 was observed on the 7th (229.75 +/- 79.05) and 21st day (98.5 +/- 11.33) with respect to day 0 (77.12 +/- 11.63). In group 2 on the 7th day of the experiment there was observed the increased levels of potassium (mmol/l) in serum (13.5 +/- 1.48) with respect to day 0 (7.74 +/- 0.88). In group 2 in the 7th (1.06 +/- 0.18) and 14th day (1.32 +/- 0.26) there was noted the decreased excretion of potassium in the urine (mmol/24h) with respect to day 0 (3.75 +/- 1.9). The decrease in serum sodium levels (mmol/l) in group 2 was recorded on 14th day (121.5 +/- 8.7) with respect to day 0 (131.62 +/- 4.07). Increased factional sodium excretion--FENa (%) was observed in group 2 on 14th day (0.25 +/- 0.06) with respect to day 0 (0.12 +/- 0.06)., Conclusions: Our main finding is that--independently of the amount bacteria present in urinary bladder--in this inflammatory model there occurs inevitably acute kidney injury, however higher bacteria amount depicts a very clear profile of laboratory parameters that point at the kidney impaired function.

The latest investigations evidence for growing number of women with urination disorders in the absence of pathological changes in the urine. This fact suggests the conclusion that dysuria may be caused by neuroendocrine disorders in such women. Besides hemodynamic disorders, urodynamic ones are also involved in pyelonephritis pathogenesis. Our investigations show that chronic non-obstructive pyelonephritis and chronic cystitis can be both a cause and a result of functional disorders of the lower urinary tract related to defects in nervous regulation. Long-term dysfunction of the lower urinary tract may provoke progressive inflammation. In this case antibacterial and anti-inflammatory treatment of chronic cystitis and chronic non-obstructive pyelonephritis may be low effective without normalization of functional condition of the urinary bladder and urethra.

The results of the treatment of 38 children (6 boys and 32 girls, age 6-14 years) with chronic pyelonephritis and/or cystitis complicated with neurogenic dysfunction of the urinary bladder (NDUB) and/or vesicoureteral reflux (VUR) of the first-third degree demonstrate efficacy of intravesical electrostimulation (IVES) and adrenal magnetotherapy. IVES was conducted with high-frequency current impulses (2.2 kHz) by means of INTRASTIM attachment to the device AMUS-01-INTRAMAG in the region of the urethrovesical anastomosis via solution of the drugs for instillation. As the result of exposure to both physical factors in the presence of standard medication, NDUB symptoms alleviated (by E.L. Vishnevsky's criteria) by 59.5% against 38.1% in the control group. Dopplerographic examination of renal vessels stated a 24.3% increase in blood flow in the major renal artery in the study group against 10.5% in the control. The proposed complex pharmacological plus physiotherapeutic treatment of chronic pyelonephritis and cystitis in abnormal urodynamics resulted in a 2.2-fold decrease in the number of recurrences compared to the standard treatment.

The paper provides literature data concerning the role of heredity, anatomico-physiological peculiarities which contribute to the chronic pyelonephritis formation in the childhood. The conditions of the infectious-inflammatory process development in the urinary tract are specified and some reasons of its chronization are mentioned. The peculiarities of the immunological reaction are analysed, as well as the role of nonimmune mechanisms, such as the lipid peroxidation process during the pyelonephritis development in the childhood.

Objective: The aim of this study was to analyze the functional urodynamic parameters, which affect renal function and can promote stone formation., Materials and Methods: We examined sixty consecutive patients with renal and ureteral stones and indication to urinary diversion by nephrostomy tube or indwelling catheter In upper urinary tract, urodynamics was assessed with the help of electromanometry and multichannel impedance ureterography. To measure ureteral peristalsis, a probe equipped with 9 successively incorporated electrodes was indwelled retrogradely into distal ureter through a urethroscope. The documented data included renal pelvic pressure (RPP) and the number of ureteric contractility parameters such as peristalsis amplitude, peristalsis rate, the ureteral wall tone, the characteristics of contractile waveform and its direction (antegrade or retrograde). Urinary biochemistry and enzymuria were studied in order to characterize the lithogenic activity and renalfunction. The patients were divided into three groups: group 1 included patients with acute pyelonephritis caused by unilateral stone obstruction (n = 24), group 2 patients with stones and non-acute latent chronic pyelonephritis (n = 31) and group 3 unobstructed patients without signs of inflammation (n = 5)., Results: In the three groups of patients, the mean baseline RPP values were, respectively 28.7 +/- 2.6 (range 20.0-32.4); 15.6 +/- 1.9 (range 3.5-29.0); and 3.6 +/- 1.4 (range 0-8) cm H2O. The ratio of GGT to urinary creatinine changed similarly: it was elevated during acute inflammation, moderately enhanced during the chronic process, but significantly decreased after stone removal and resolution of inflammation (11.5 +/- 3.2; 8.1 +/- 2.0, and 1.6 +/- 0.5 unit/L). Biochemical evaluation revealed 54% patients with enhanced lithogenic activity assessed by elevated calcium and oxalates in the urine (4.95 +/- 0.25 mM and 504 +/- 35 microM, correspondingly) and low level of citrates (2.5 +/- 0.1 mM). In a subgroup of 11 patients with urolithiasis the baseline RPP values were assessed in relation to ureteral contractile activity in the distal region of ureter. Low RPP was found in a patient (9%) with strong ureteral contractions and a low tone while RPP was moderately higher in another patient (9%) with moderate mean peristaltic amplitude value but with elevated tone of ureteral wall. In the majority of examined patients with significantly elevated mean RPP value (45%), peristalsis of distal ureter was characterized by weak long-term and frequent contractions as well as increased tone with respect to the patients with normal RPP. The patients (36%) with moderately increased RPP demonstrated strong frequent contractions in the distal ureter and low ureteral wall tone. Changes in urodynamic parameters in patients examined before and immediately after ureteroscopy and lithotripsy procedures were observed. Factors affecting the ureteral wall tone were duration of stone disease, location and disposition of stones., Conclusions: Our clinical observations obtained with the help of physiological methods revealed various factors modulating the urodynamic disorders in renal pelvis: temporary or persistent elevation of pelvic pressure; peculiarities of contractile function in distal ureter manifested by the tonic changes and variations in contractile amplitude, and certain abnormalities in propagation of contractile wave in the upper urinary tract. The reported urodynamic changes in patients with stone disease can be supplementary pathogenic factors causing deterioration of renal function probably followed by stone formation.

Acute pyelonephritis is one of the most common indications for antepartum hospitalization. When acute pyelonephritis is diagnosed, conventional treatment includes intravenous fluid and parenteral antibacterial administration. There are limited data by which to assess the superiority of one antibacterial regimen over the other in terms of efficacy, patient acceptance and safety for the developing fetus; however, it is important to consider antimicrobial resistance patterns in the local community when choosing an agent. Moreover, there are growing public health concerns regarding antimicrobial resistance to commonly prescribed medications for urinary tract infections in pregnancy. There is a small body of evidence to support the ambulatory treatment of pregnant women with pyelonephritis in the first and early second trimesters, but the majority of women will be managed as inpatients. This article provides a suggested algorithm for the treatment of pyelonephritis during pregnancy.

Hyperbaric oxygenation (HBO) was used in combined treatment of 66 patients with acute pyelonephritis. In 29 of them with primary pyelonephritis it was a part of conservative treatment. In 37 patients with secondary pyelonephritis HBO was applied postoperatively. A HBO course comprised 8-10 sessions under pressure 2.0-2.4 atm for 60 min. It was found that frequency of surgical interventions in HBO administration reduced by 36.2%. Postoperative HBO administration decreased hospital stay by 16.9%. Mechanisms of HBO positive action operate through attenuation of systemic inflammatory reaction and polyorganic insufficiency 1.62 and 2.9-fold, respectively, decline of intoxication in growing glomerular filtration rate and improvement of renal hemodynamics. Moreover, HBO promotes recovery of the immune status. In experiment on 40 white rats with acute pyelonephritis HBO decreased inflammation in renal tissue.

Purpose: The pathophysiology, evaluation, description and clinical implications of renal damage associated with vesicoureteral reflux remain controversial. We summarized the current understanding of this important aspect of clinical vesicoureteral reflux., Materials and Methods: We performed a detailed review of the literature on clinical, pathological and experimental data related to congenital vesicoureteral reflux and bladder dynamics. We also reviewed the clinical context and imaging evaluation with underlying experimental data related to post-infectious reflux nephropathy., Results: Congenital reflux nephropathy is a pattern of impaired renal function and development with renal dysplasia as the most severe but not the only form. Mechanisms of developmental disruption are potentially related to vesicoureteral reflux dynamics during gestation and associated bladder dynamics, which may continue into postnatal life. Acquired renal injury associated with infection is related to particular bacterial and host factors that determine infection virulence, host inflammatory response and tissue recovery. As best seen on dimercapto-succinic acid scan, acute changes may resolve but may also persist as permanent renal scarring. Specific risk factors for acute pyelonephritis and renal scarring in patients with vesicoureteral reflux include higher reflux grade, dysfunctional voiding/elimination, recurrent pyelonephritic episodes and delayed initiation of antibiotic therapy. Low pressure sterile reflux is not a cause of reflux nephropathy., Conclusions: Renal damage associated with vesicoureteral reflux may be congenital or acquired and the respective pathophysiological mechanisms are likely different. Congenital damage is often dysplasia, which may be a result of disordered renal development secondary to significant alterations in bladder dynamics. These processes may continue into the newborn period while kidney maturation continues. Recognizing the clinical potential for ongoing effects on renal function and the role of bladder development are important for clinical care. Post-pyelonephritic acquired damage is the result of a complex interaction of host and bacterial factors that leads to acute alterations in renal function, and may lead to permanent renal scarring. Strategies for timely intervention as well as prevention are essential to limit the risk of permanent renal injury, which may predispose to hypertension and renal insufficiency in some patients., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Pregnant women with pyelonephritis (PN) and glomerulonephritis (GN) were shown to have response to the therapy in accordance with level of kidney functional activity. The women with PN and GN have the treatment efficacy higher with Kidney Functional Reserve KFR > 10% and from 5 to 10% and practically absent in pregnant women with KFR < 5% (Kidney functional reserve).

No clear explanation exists to understand how sex hormones and/or chromosomes affect the immune system. In vitro studies of human lymphoid cells also show sex differences in immune function. To evaluate these differences in frequent pediatric emergencies, we analyze the expression of inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, and neutrophil count) underlying inflammatory processes in children: 482 children (241 girls and 241 boys) hospitalized for pneumonia (n = 384), pyelonephritis (n = 39), or bronchiolitis (n = 59) matched for age and sex. All patients were younger than 10 years. A control population of 97 children (50 girls and 47 boys) admitted for day surgery (tonsillectomy, circumcision, or strabismus) was included. We observed highly significant differences between girls and boys: median C-reactive protein concentration of 5.45 mg/dL (range, 0.2-36.0 mg/dL) for girls and 2.6 mg/dL (range, 0.3-37.3 mg/dL) for boys (P < 0.0001), and median erythrocyte sedimentation rate of 39.5 mm/h (range, 2-104 mm/h) for girls and 24 mm/h (range, 4-140 mm/h) for boys (P < 0.005). Neutrophil counts were also significantly different: a median of 8,796 cells/microL (range, 328-27,645 cells/microL) for girls and 6,774 cells/microL (range, 600-38,668 cells/microL) for boys (P < 0.02). The duration of fever after initiating antibiotic therapy was longer in girls than in boys, but there was no difference (Fisher exact test, P < 0.06). The present study documents a relationship between sex and both the production of inflammatory markers and neutrophil recruitment. Sex difference also showed more direct clinical relevance with associations seen between sex and both duration of fever and duration of disease (bronchiolitis P < 0.0007).

A mitochondria-targeted chimeric compound consisting of a rhodamine derivative linked to a plastoquinone molecule (10-(6'-plastoquinonyl)decylrhodamine, SkQR1) was studied under conditions of acute brain or kidney damage. A protective effect of this compound was demonstrated in a model of focal brain ischemia, rat kidney ischemia/reperfusion, myoglobinuria (rhabdomyolysis, or crush syndrome), and pyelonephritis. We found that a single intraperitoneal injection of SkQR1 diminishes the size of the ischemic zone in the brain and improves performance of a test characterizing neurological deficit in ischemic animals. Control substance not containing plastoquinone appeared to be not neuroprotective. The data show that SkQR1 is a nephroprotectant and neuroprotectant, which can be due to the antioxidative action of this Skulachev cation.

The investigations performed have shown, that in the general structure among all the pregnant women with CP and CG the share of frequency of PE grows depending on the degree of FKR Thus, the estimation of the FKR in the debut of pregnancy in the women with CP and CG has basic importance not only for the prognosis but also for assessment of the efficacy of the therapy performed.

Background: On the basis of cardiovascular compliance, hemodialysis (HD) patients can be classified as hypotension prone (HP) or hypotension resistant (HR)., Methods: We compare the hemodynamic behavior and myocardial performances in 6 HP and 6 HR patients before and after an isolated ultrafiltration (IU) session removing 3% of total body water., Results: HP show higher basal plasma angiotensin II levels during IU (p<0.01), whereas angiotensin II remained unchanged in HR patients (p<0.001 between groups). The percentage changes of plasma volume (PV) was similar in the 2 groups. A significant reduction of cardiac index was observed only in the HP group (p<0.001 between groups). The mean values of heart rate remained significantly higher, whereas total peripheral resistances significantly fell in the HP in comparison with the HR group (p<0.001 between groups). During IU, the mean arterial pressure (MAP) changes were -10 +/- 3 mm Hg in the HP vs. -3.3 +/- 2 mm Hg in the HR group (p<0.001). Echocardiography data were collected before and after IU. All enrolled patients presented left ventricular hypertrophy; following IU, HP patients showed a reduction of mean left ventricular diameter (p<0.01), left atrial diameters and right atrial diameter, and a change in percentage of right atrium ejection fraction (p<0.001, p<0.01)., Conclusions: In comparison with HR patients, HP patients before and after IU showed a defective arteriovenous tone adjustment to the PV changes, with a hemodynamic picture of abnormal sympathetic stimulation. Moreover, a reduced cardiac preload with both atrial and ventricular underfilling in these patients is at risk for a sudden drop in MAP.

The paper is devoted to the key problems of etiology and pathogenesis of chronic pyelonephritis in children. Factors responsible for the development of primary and secondary pyelonephritis are discussed. Including urinary tract obstruction. The main stages of pathogenesis are considered with reference to the mechanisms of uropathogenic action of bacterial agents of pyelonephritis.

Background: To determine urodynamic, behavioral and functional abnormalities predisposing to recurrent urinary tract infection in 5- to 17-year-old girls., Methods: A prospective case-control study was carried out. A total of 148 girls met inclusion criteria. They received a careful evaluation including complete history, voiding-drinking diary, bowel questionnaire, physical investigation, sonography, voiding cystourethrogram and urodynamic investigation., Results: In a multivariate model, independent risk factors for recurrent urinary tract infection included age 20 mL (OR=1.1; 95% CI, 1.0-1.1)., Conclusions: Independent risk factors for recurrent urinary tract infection were age

The investigations performed showed that in the pregnant women with CP and CG there is noted response to therapy performed in accordance with level of kidney function activity. In the pregnant women with CP and CG the treatment efficacy was higher in pregnant women with KFR > 10% and from 5 to 10% and from 5% to 10%, and practically absent in pregnant women with KFR < 5%.

Background: : Acute lobar nephronia (ALN) is a complicated acute renal infection that is part of the progression of the inflammatory process of acute pyelonephritis that can progress to renal abscess if left untreated. We examined the place of ALN in the spectrum of upper urinary tract infections., Methods: : The medical records of all patients diagnosed with ALN by computed tomography (CT) were reviewed retrospectively in terms of their demographic characteristics, clinical presentations, and laboratory findings. The patterns of the ALN lesions were checked on all contrast-enhanced CT films and the volume of the CT lesions (the extent of renal involvement) was estimated in every patient. Then, the correlation between the clinical presentation and CT lesions was examined., Results: : Two distinct CT patterns of ALN lesions were observed in 127 patients: 94 simple ALN and 33 complicated ALN. Simple ALN appeared as striated or wedge-shaped, poorly defined regions of homogeneously decreased nephrographic density, whereas the lesions of complicated ALN showed heterogeneously decreased nephrographic density after contrast enhancement. The volume fraction of the CT lesions correlated well with the duration of fever before (P = 0.006) and after (P < 0.001) treatment in patients with simple ALN, while only the correlation between the fever duration after treatment and the volume fraction of the CT lesions (P < 0.001) was significant in patients with complicated ALN. Patients with complicated ALN were generally older (P = 0.004) and febrile longer after starting antibiotic treatment (P < 0.001). All treatment failures were in the complicated ALN group., Conclusions: : Children with ALN comprise 2 groups with different clinical presentations and treatment responses: simple ALN and complicated ALN. We suggest that simple ALN be regarded as a continuation of acute pyelonephritis and require 2 weeks of antibiotic treatment, while complicated ALN is a distinct more severe form requiring a 3-week or longer therapy regimen as the treatment of choice.

Vesicoureteral reflux may be associated with abnormalities of the renal parenchyma. The purpose of this review is to define what the parenchymal abnormalities are histologically, what their etiologies may be, how they are identified and what their long-term clinical impact may be. Two categories are recognized, renal dysplasia and post-infection, chronic pyelonephritis. The diagnostic gold standard is microscopic evaluation of biopsy specimens but renal scintigraphy can be used in the diagnosis of renal dysplasia versus chronic pyelonephritis. Potential long-term sequelae of reflux nephropathy include hypertension and renal insufficiency although these may occur infrequently. A review of the current literature is provided.

The kidneys of the patients with purulent pyelonephritis (PP) undergo anatomic and functional alterations. The latter may be irreversible in some cases. The severity of the above alterations depends on PP form, choice and time of treatment. Our study included 84 patients who had PP at the age of 15 to 70 years. Primary PP was detected in 47 (56%) patients, secondary--in 37 (44%) patients. Open surgery was performed in 18 patients (group 1), transcutaneous drainage was used in 38 patients (group 2), conservative treatment was conducted in 28 patients (group 3). Comparison of dynamic nephroscintigraphic findings showed that recovery of renal function in groups 2 and 3 lasted 6-12 months versus 60-84 months in group 1. The degree of the renal function recovery depends on the PP form, age of the patient, duration of the disease, virulence of the causing agent, comorbid pathology, immune status, method of treatment. This was confirmed by the data of complex radionuclide examination. Long term complications, for instance, progress of arterial hypertension (41% cases) and chronic pyelonephritis (44% cases) were observed more frequently and earlier in patients after open operations.

Acute uncomplicated pyelonephritis (APN) is a complex clinical entity, which is defined differently based on clinical or imaging criteria. The aim of this study was to describe the clinical and radiological presentation of APN-upper urinary tract infection (UTI) cases observed between May 2005 and June 2006 and hospitalised in the Emergency Medicine ward of San Luigi Hospital, Orbassano, Turin, Italy. All patients underwent imaging scans and were differentiated on the basis of parenchymal involvement. Of around 45000 patient visits to the emergency room between May 2005 and June 2006, 23 patients were diagnosed as having uncomplicated upper UTI (all female, age 15-57 years). Renal parenchymal involvement was confirmed by imaging in 16 cases (69.6%). The imaging spectrum ranged from a small single lesion to large multiple defects; on admission, 2 cases had no pain and 2 had no fever; lower urinary tract symptoms were present in only 13 patients (7 with parenchymal involvement). All patients with parenchymal involvement had at least one sign of systemic inflammation-infection. Most patients (15) had taken antibiotics before hospitalisation; consequently, urine cultures were negative in 21 cases (14 cases with positive imaging (87.5%)). The data from patients with and without parenchymal involvement overlapped, the only difference being a higher prevalence of high CRP levels in cases with parenchymal involvement.

A concept is proposed laying emphasis on the involvement of cytokines, growth factors, prostaglandins, and nitrogen oxides in the mechanism of formation of reflux-nephropathy in children. It is shown that enhanced production of mediators of inflammation and humoral growth factors in patients with vesico-ureter reflux depends on the degree of infiltrative and sclerotic changes in the kidneys. The accompanying dysbalance of pro- and anti-inflammatory cytokines due to increased endogeneous production of TNF-alpha and concomitant decrease of daily BL-10 excretion constitutes an unfavourable prognostic factor of reflux-nephropathy. There is evidence that inclusion of ACE inhibitors (Enap) in therapy of vesico-ureter reflux during 6 months leads to a marked improvement of the structural and functional state of the kidneys. It suggests high renoprotective potential of these preparations and the possibility of their use for prophylaxis of nephrosclerosis in children.

MR urography has the potential to significantly improve our understanding of the relationship between reflux nephropathy, pyelonephritis, vesicoureteric reflux and renal dysplasia. MR urography utilizes multiple parameters to assess both renal anatomy and function and provides a more complete characterization of acquired and congenital disease. Pyelonephritis and renal scarring can be distinguished by assessing the parenchymal contours and signal intensity. Characteristic imaging features of renal dysplasia include small size, subcortical cysts, disorganized architecture, decreased and patchy contrast enhancement as well as a dysmorphic pelvicalyceal system. Because of its ability to subdivide and categorize this heterogeneous group of disorders, it seems inevitable that MR urography will replace DMSA renal scintigraphy as the gold standard for assessment of pyelonephritis and renal scarring. MR urography will contribute to our understanding of renal dysplasia and its relationship to reflux nephropathy.

The objective of this study was to evaluate the role of urolithiasis, infection, and bladder dysfunction in the pathogenesis of renal failure in rats subjected to supratrigonal cystectomy. One group of Sprague-Dawley rats was submitted to supratrigonal cystectomy, a second to cystectomy during which a suspension of Proteus mirabilis was injected into the bladder stump, and a third to sham surgery (controls). The animals were sacrificed two months after surgery. Blood pressure and serum urea and creatinine were measured before surgery and at sacrifice when a careful inspection of the urinary tract was performed to determine the presence of hydronephrosis and calculi. Microbiological analyses were performed on urine aspirated from the bladder and on the kidneys. Significant differences were found between values of systolic blood pressure and serum urea and creatinine recorded prior to the surgical procedure and those recorded at sacrifice in each group except the control group. Renal failure was present in all animals subjected to cystectomy. Urinary calculi were documented in 5/10 animals subjected to cystectomy only and in all rats inoculated with P. mirabilis. Hypertension was documented in 43.75% of animals subjected to cystectomy. Pyelonephritis was diagnosed only in animals with urinary calculi, in each of which urine culture was also positive. No cases of renal failure, hypertension, calculi, and/or pyelonephritis were detected in the sham group. The findings of this study indicate that kidney failure in rats subjected to supratrigonal cystectomy is related to the severe bladder dysfunction induced by the surgical procedure.

We report the case of a 50-year-old man who presented to our institution with septic thrombosis of the renal vein which had not resolved despite several days of antibiotic therapy. Optimal restoration of renal vein flow was obtained by percutaneous manual aspiration embolectomy (PMAE) in this patient with contraindication to fibrinolytic therapy and surgery.

P fimbria, a mannose-resistant adhesin of uropathogenic Escherichia coli (UPEC), has been shown to be associated with acute pyelonephritis. The pap gene cluster encodes the proteins required for P-fimbrial biogenesis, including papG, which encodes the tip adhesin. The three most studied PapG molecular variants, which are shown to bind distinct isoreceptors, are PapGI, -II, and -III. PapGII preferentially binds globoside, or GbO4, a glycolipid isoreceptor of the human kidney. Studies using different animal models of ascending urinary tract infection (UTI) have demonstrated a variable role for P fimbriae, and specifically PapGII-mediated adherence, in renal colonization. The disparities in the results obtained from those studies are likely to be attributed to the differences in animal models and UPEC strains utilized. One explanation that is discussed in detail is the contribution of multiple fimbriae of UPEC that potentially mediate adherence to the mammalian kidney. Overall, P fimbriae appear to play some role in mediating adherence to uroepithelial cells in vivo and establishing an inflammatory response during renal colonization, thus contributing to kidney damage during acute pyelonephritis. To verify that P fimbriae contribute to the pathogenesis of UPEC during ascending UTI (and in particular acute pyelonephritis), future studies should be conducted to satisfy fully all three tenets of the molecular Koch's postulates, including complementation of a mutated allele.

The aim of this study was to define in children younger than 2 years of age the diagnostic significance of clinical and laboratory findings to localize site of febrile urinary tract infection. We reviewed the records of 185 children younger than 2 years of age admitted to hospital with febrile urinary tract infection. Patients were divided into having either acute pyelonephritis or acute cystitis according to the presence or absence of acute lesions on dimercaptosuccinic acid (DMSA) renal scintigraphy. Clinical and laboratory [white blood cell count (WBC), urinalysis, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)] findings were compared between the two groups using Student's t test, chi-square test, and multivariate analysis. Patients with pyelonephritis had statistically significant higher age, WBC, ESR, and CRP than those with cystitis. Although the sensitivity of the tests was 80-100%, their specificity was <28%. On multivariate analysis, 33% of patients with cystitis were diagnosed as having pyelonephritis, whereas 22% of those with pyelonephritis were considered to have cystitis. Given the low specificity of clinical findings and available laboratory tests to define the site of urine infection in this age group, we recommend DMSA renal scintigram as the test of choice to make the diagnosis of acute pyelonephritis in these patients.

Urodynamics was studied in patients with chronic pyelonephritis with a various level of upper urinary tract (UUT) obstruction. 90% patients with concrements of the low ureter had high intrapelvic pressure (IPP)--21.8 +/- 0.8/25.2 +/- 0.8 cm of water column (basal/peristaltic) and enhanced UUT contractility. IPP was elevated in 50% patients with proximal UUT obstruction (11.8 +/- 1.3/15.5 +/- 1.5 cm of water column) and it rose noticeably (by 110-184%) in changing body position (orthostatic test) but changed little in the respiratory test. High IPP persisted despite functioning nephrostomic drainages in 84-86% patients exposed to extracorporeal and/or contact lithotripsy at the average level 16.2 +/- 0.8/19.7 +/- 0.6 cm of water column. Different mechanisms may be involved in formation of high IPP in patients with chronic pyelonephritis and varying level of UUT obstruction. In view of damaging influence of high IPP on renal function the physician should control this index during the treatment and take additional measures to prevent elevation of IPP.

Investigations performed by the authors proved pathogenetic validity of interference therapy of chronic pyelonephritis in children. A course of interference currents has a positive effect on partial renal functions, excretion of beta2-microglobulin, urodynamics of the lower urinary tract, humoral and cell links of immunity, lipid peroxidation in red cell membranes. Advantages of interference currents impact on the reflex-segmentary zone and urinary bladder projection area in children with concomitant neurogenic dysfunction of the urinary bladder are shown.

We studied urodynamics of the upper urinary tract in a different course of renal inflammation with consideration of the drainage method. Pressure in the renal pelvis was measured in 64 patients with acute obstructive and non-obstructive, and chronic pyelonephritis in different time of establishment of surgical or transcutaneous puncture nephrostomas and ureteral catheters. We assessed changes in intrapelvic pressure in respiratory (regular and forced respiration) and orthostatic (lying, sitting, standing positions) functional tests. The autonomic status of the body was evaluated by parameters of the spectral analysis of heart rate variability. We have found that intrapelvic pressure increases with progression of renal inflammation. Dynamics of the above indices in patients with acute non-obstructive and obstructive pyelonephritis versus patients with renal colic in the absence of evident inflammation allowed us to specify mechanisms of pressure formation in renal pelvis including inflammatory edema of the parenchyma and nervous-reflectory links of upper urinary tract regulation. Pressure in the renal pelvis may serve an important diagnostic criterion in choice of renal drainage method in pyelonephritis and criterion of inflammation course prognosis.

Background: Bacteremia has been considered as a surrogate marker of severe infection in several infectious diseases. However, it remains uncertain whether the presence of bacteremia correlates with severe infection in patients with complicated acute pyelonephritis (APN)., Methods: We performed a retrospective study to investigate the relationship between the presence of bacteremia and disease severity in complicated APN. To do this, we reviewed medical records from 128 patients diagnosed with complicated APN admitted to Kaohsiung Veterans General Hospital, Taiwan between January, 2003 and December, 2003. In our analysis, we compared clinical presentation, treatment response, and outcome in patients with and without bacteremia., Results: Fifty-four of 128 patients (42%) were bacteremic. This group of patients presented more frequently with severe sepsis or septic shock (P < 0.001), compared with nonbacteremic patients. Other factors that correlated with the presence of bacteremia were older age, diabetes mellitus, more band forms in neutrophil cell counts, impaired renal function, and a lower level of serum albumin. Using a multivariate logistic regression analysis, we show that lower levels of serum albumin (odds ratio, 0.18; 95% CI, 0.05-0.65; P = 0.008) and presence of severe sepsis (odds ratio, 4.76; 95% CI, 1.43-15.84; P = 0.011) were independent factors associated with bacteremia. Following treatment, the bacteremic group took a longer time to become defervescent than the nonbacteremic group (5.1 +/- 2.3 vs. 4.2 +/- 1.6 days, P = 0.023). Also, the bacteremic group had a greater mean duration of intravenous antibiotics administration and longer hospital stays (P < 0.001). Multiple logistic regression analysis shows that non-Escherichia coli bacteremia, presence of urolithiasis or hydronephrosis, shorter duration of antibiotics administration, and being male were significantly associated with recurrence of urinary tract infection within 6 months., Conclusion: Bacteremia in cases of complicated APN indicates a severe disease, which is more likely to recur in patients with non-E coli bacteremia. Our study showed that bacteremia is indeed a useful clinical indicator of severe disease and, if found, should influence patient management. Therefore, we recommend that blood culture samples should be taken in all patients with complicated APN.

Human patients with renal disease frequently develop disturbed sleep and severe fatigue. To develop a model for studying factors that contribute to these symptoms, we characterized the sleep patterns of various strains of mice after acute challenge with the fungal organism Candida albicans. After intravenous administration to mice, C. albicans typically colonizes the kidney, producing acute pyelonephritis. Various strains of inbred mice demonstrate marked variation in the temperature and sleep responses that develop after challenge, with individual strains generally showing increased or reduced somnolence in association with fever or hypothermia, respectively. C. albicans-infected mice may be a useful model for identifying the genes and mechanisms that link sleep, temperature, fatigue, and the immune response.

Children with acute pyelonephritis develop polyuria and have reduced maximum urinary concentration capacity. We studied whether these abnormalities are associated with altered urinary excretion of the water channel aquaporin-2 (AQP2) in the renal collecting duct. AQP2 is the main target for antidiuretic action of arginine vasopressin (AVP), and the urinary excretion of this protein is believed to be an index of AVP signaling activity in the kidney. Children with acute pyelonephritis, aged 5-14 years, were examined for urinary flow rate, creatinine clearance, unchallenged urine osmolality, and urinary ion excretion. Urinary excretion of AQP2 was measured by dot immunoblotting technique. Studies were performed in the acute phase of pyelonephritis, in the same children after treatment, and in control patients. At the onset of pyelonephritis, urinary flow rate and solute excretion were increased, but the urinary osmolality was unchanged. The urinary level and urinary excretion of AQP2 was increased in acute pyelonephritis and decreased after treatment. Excretion of aquaporin-3 was unchanged, suggesting that the increase in AQP2 urinary excretion was not due to a shedding of collecting duct cells. The results suggest that a mechanism proximal to the collecting duct may be responsible for the polyuria observed in children with acute pyelonephritis. Increased urinary AQP2 levels suggest that a compensatory activation of apical plasma membrane targeting of AQP2 may occur in pyelonephritis.

Background: Scarring is one of the steps of excessive wound healing, causing dysfunction of the involved tissues and clinically poor cosmetics. The aim of this study was to examine the effect of a highly selective cyclooxygenase-2 (COX-2) inhibitor on renal scar formation in experimental pyelonephritis., Materials and Methods: Four groups of 10 Balb/C mice were formed. In groups I and II following the inoculation of lipopolysaccharide (LPS) into both kidneys, 0.18 and 0.36 mg/day of rofecoxib was given respectively via intraperitoneal route for 5 days. No medication was applied following physiological saline solution injection to both kidneys of the mice in group III (negative control group). After group IV's LPS inoculation on the first day, saline solution (1 ml/day) was given intraperitoneally for 5 days (positive control group). Following the exposure of both kidneys, LPS of Escherichia coli (5 mg/kg) was injected into the kidneys of groups I, II, and IV. In group III, saline solution (0.1 ml) was used instead of LPS. Three days after the inoculation of LPS, solutions containing 0.18 and 0.36 mg of COX-2 inhibitor were given intraperitoneally for 5 days in groups I and II. No medication was used for the mice in group III. Six weeks after the inoculation of LPS and saline solution, all mice were humanely euthanized. Bilateral nephrectomies were done on each group of mice, and histopathological examination was performed., Results: Inoculation of LPS into the renal parenchyma caused pyelonephritis and scar formation in all groups. The degree of pyelonephritis and scar formation was lesser in groups in which COX-2 inhibitors were used. The degree of scar formation was lesser in group II, in which 0.36 mg more of COX-2 inhibitor was used than in group I (0.18 mg of COX-2 inhibitor)., Conclusion: In our study model, direct inoculation of LPS to kidneys caused experimentally induced pyelonephritis. Renal scar formation was effectively prevented through the utilization of rofecoxib at 0.36-mg doses., (Copyright (c) 2006 S. Karger AG, Basel.)

The role of the kidney in the control of blood pressure has been convincingly demonstrated by several studies. Recent evidence has suggested that subtle acquired tubulointerstitial injury may cause a defect in sodium excretion function, thus leading to salt-sensitive hypertension. There are no reports, however, examining the effect of experimental chronic pyelonephritis on renal sodium handling and arterial pressure. Thus, to examine the influence of salt intake and unilateral nephrectomy, unanesthetized, unrestrained rats were randomly assigned to one of two separate groups: sham-operated rats (CO) or chronic unilateral pyelonephritic rats (CP). After twenty one days, the pyelonephritic group was subdivided in two: one subgroup continued with water intake (CPw), while the other was changed to 0.9% NaCl intake (CPs), like the control group (COs). After seven days, all rats were submitted to unilateral nephrectomy of the left normal kidney. Data presented herein show that chronic pyelonephritis produced an increase in mean arterial pressure (CO: 121.4 +/- 1.0 mmHg to CP: 127.0 +/- 0.9 mmHg, p = 0.000) that was enhanced by saline ingestion (COs: 121.6 +/- 1.4 mmHg; CPw: 127.0 +/- 1.8 mmHg; CPs: 132.1 +/- 1.2 mmHg, p = 0.000) and further aggravated by unilateral nephrectomy (CO: 125.2 +/- 2.6 mmHg; CPw: 127.5 +/- 0.9 mmHg; CPs: 139.2 +/- 1.1 mmHg, p = 0.000). Unchanged blood pressure measurements (120.2 +/- 2.3 mmHg) were observed beyond 21 days in control rats maintained on water regimen when compared with saline-drinking groups. These changes in mean arterial pressure were observed despite an increased fractional sodium excretion in the CPs group compared to the other groups before uninephrectomy (COs: 0.125 +/- 0.025%; CPw: 0.045 +/- 0.013%; CPs: 0.292 +/- 0.046%; p = 0.000), as compared to CPw after uninephrectomy (COs: 0.249 +/- 0.077%; CPw: 0.062 +/- 0.011%; CPs: 0.363 +/- 0.195%, p = 0.019). In addition, it was shown that daily liquid intake was higher in CPs than in CPw but similar to COs, both before uninephrectomy (COs: 42.8 +/- 2.6 ml/d; CPw: 34.3 +/- 3.5 ml/d; CPs: 51.8 +/- 3.7 ml/d, p = 0.006) and after uninephrectomy (COs: 40.9 +/- 5.5 ml/d; CPw: 33.8 +/- 1.4 ml/d; CPs: 53.0 +/- 3.5 ml/d, p = 0.004). The current data suggest that chronic pyelonephritis promotes an inability of renal tubules to handle sodium excretion when exposed to sodium overload and aggravated by uninephrectomy, thus constituting a model for salt-sensitive hypertension.

Bone morphogenetic protein 7 (BMP 7) is a member of the transforming growth factor (TGF) beta superfamily and is involved in regeneration, repair, and development of specific tissues, for example kidney, gut, lens, and skeleton. BMP 7 has emerged as a renotrophic factor and experimental studies have shown its protective role against fibrotic processes. Tubulointerstitial changes are present in the pyelonephritic kidney which progresses to fibrosis. Renal fibrosis may lead to significant morbidity in the form of hypertension, proteinuria, and loss of renal function. The objective of this study was to investigate BMP 7 expression in experimental acute and chronic pyelonephritis models. Eighteen Wistar rats were injected with 0.1 mL solution containing E. coli ATCC 25922 10(10) cfu mL(-1) into left renal medullae. Six rats were used as a sham group and were given 0.1 mL 0.9% NaCl. Pyelonephritic rats were sacrificed 24 h (group I, n=6), 1 week (group II, n=6), and 6 weeks (group III, n=6) after E. coli injection. Serum creatinine levels were analyzed. Renal tissues were studied histopathologically by use of hematoxylin and eosin and scored for diagnosis of pyelonephritis. BMP 7 expression was studied semiquantitatively by immunohistochemical staining. Acute (group I) and chronic (group II and group III) pyelonephritic histopathological changes were observed in experimental pyelonephritic groups. A gradual decrease in BMP 7 expression was observed in the tubulointerstitial and tubular area of the pyelonephritic kidneys, mildest in the acute pyelonephritic group and most severe in the chronic pyelonephritic 6th week group. A statistically significant difference was observed between tubulointerstitial BMP 7 expression by groups I and III (P=0.017) and by groups III and IV (P=0.000). Tubular BMP 7 expression was statistically significantly different between groups II and IV (P=0.009) and between groups III and IV (P=0.002). The data imply that BMP 7 has a major role in chronic pyelonephritis. Tubulointerstitial and tubular BMP 7 expression also had a significant negative correlation with fibrosis, tubular, atrophy, and vascular changes. Serum creatinine levels of the study group were all normal. We conclude that the decrease in renal BMP 7 expression in experimental chronic pyelonephritis is one of the factors responsible for fibrotic changes in persistent renal damage.

Tamm-Horsfall glycoprotein (THP) is the most abundant protein which is synthesized by renal tubular cells and excreted in urine. Its role in urinary tract infection has yet not been identified. In the present study, the contribution of THP towards adherence of Pseudomonas aeruginosa to uroepithelial cells and murine peritoneal macrophages was studied. Decreased adherence of THP-coated P. aeruginosa to UECs and phagocytes was observed in vitro. In vivo, P. aeruginosa showed increased renal bacterial load and tissue pathology in a mouse model of acute ascending pyelonephritis, when THP-coated P. aeruginosa was used to cause infection. This study shows that THP may not necessarily act as a host defense component; rather, it may help in renal colonization of P. aeruginosa in vivo.

The pathogenic mechanism of recurrent or chronic urinary tract infection is poorly understood. Escherichia coli cells bearing Dr fimbriae display unique tropism to the basement membrane (BM)-renal interstitium that enables the bacteria to cause chronic pyelonephritis in experimental mice. The renal receptors for Dr-fimbriated E. coli are type IV collagen and decay-accelerating factor (DAF). We hypothesized that type IV collagen receptor-mediated BM-interstitial tropism is essential for E. coli to cause chronic pyelonephritis. To test the role of the type IV collagen tropism of Dr-fimbriated E. coli in renal persistence, we constructed an isogenic mutant in the DraE adhesin subunit that was unable to bind type IV collagen but retained binding to DAF and examined its virulence in the mouse model. The collagen-binding mutant DrI113T was eliminated from the mouse renal tissues in 6 to 8 weeks, while the parent strain caused persistent renal infection that lasted at least 14 weeks (P < or = 0.02). Transcomplementation with the intact Dr operon restored collagen-binding activity, BM-interstitial tropism, and the ability to cause persistent renal infection. We conclude that type IV collagen binding mediated by DraE adhesin is a critical step for the development of persistent renal infection in a murine model of E. coli pyelonephritis.

The evolution and the relationship between inflammatory and renal-injury markers in women with acute uncomplicated pyelonephritis under antimicrobial therapy were investigated in a prospective study. Markers were measured before and 6 and 24 h after the intravenous administration of 1 g of ceftriaxone. Before treatment, the median levels of all markers except the serum creatinine levels were high. Twenty-four hours after the onset of antibiotic treatment, the C-reactive protein (CRP) level continued to be high, while the serum interleukin-6 (IL-6) levels and the urine IL-6, IL-8, albumin, and immunoglobulin G (IgG) levels decreased significantly. In contrast, serum creatinine and tumor necrosis factor alpha levels and urine N-acetyl-beta-glucosaminidase, alpha1-microglobulin, and beta2-microglobulin levels did not change over time. There was a significant correlation between IL-6 and IL-8 levels and urine albumin and IgG levels (urine albumin and IgG levels are glomerular and urinary tract-injury markers) as well as between serum CRP levels and the levels of the tubular-injury markers. In women with acute pyelonephritis, appropriate antibiotic treatment rapidly decreases serum IL-6 levels and urine IL-6 and IL-8 levels, which correlate well with urine albumin and IgG levels.

Urinary levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) higher than those of matrix metalloproteinase 9 (MMP-9) during acute pyelonephritis have previously been associated with a higher degree of acute inflammation and of postinfective renal scarring. The aim of the present study was to evaluate possible mechanisms by which TIMP-1 could affect the scarring process already during the acute phase of inflammation. The growth of Escherichia coli, bactericidal activity of fresh human blood, and respiratory burst, spontaneous apoptosis, and trans-basement membrane migration of normal human granulocytes were studied in vitro in the presence of different concentrations of recombinant human TIMP-1. To imitate the "normal" environment during inflammation in the kidney, granulocytes were also incubated with a conditioned medium from E. coli-stimulated renal epithelial cells. In order to compare our data with the in vivo situation, blood and urinary leukocyte levels were analyzed for 40 children with acute pyelonephritis, together with urinary MMP-9 and TIMP-1 levels. TIMP-1 at a concentration of 500 ng/ml increased the bactericidal activity of blood, increased the respiratory burst of granulocytes, decreased phosphatidylserine exposure and caspase 3 activity, which are features of spontaneous apoptosis, and inhibited granulocyte transmigration. Moreover, in the patients with pyelonephritis, MMP-9/TIMP-1 ratios in urine correlated with the degree of leukocyte transmigration. Thus, our data suggest that TIMP-1 specifically blocks the transmigration of granulocytes into urine. Entrapped and activated granulocytes, protected from apoptosis, might excessively destroy renal parenchyma and thus contribute to the pathogenesis of renal scarring following acute pyelonephritis.

Aim: To study clinicobiochemical features of chronic pyelonephritis (CPN) in the population of northen areas of the Tyumen Territory; to determine emoxipine effects on CPN treatment efficacy., Material and Methods: Clinicolaboratory manifestations of CPN were studied in 246 CPN patients (126 residents of the Tyumen South and 120 residents of the Tyumen North, age 18-55, 174 females, 72 males). The control group consisted of 60 healthy subjects of the same gender and age., Results: CPN in patients living in the north was characterized by more severe intoxication, dysuric disorders, piuria, arterial hypertension, more intensive restructuring of cellular membranes. Membranopathological changes depend on the phase of the pathological process and clinical form of the disease. Emoxipin addition to combined therapy of CPN promoted faster correction of basic CPN symptoms and stabilization of the lipid phase of erythrocytic membranes., Conclusion: Clinical and biochemical features of CPN in patients living in the Tyumen North represent additional diagnostic criteria of the disease activity. Adjuvant use of the antioxidant drug emoxipin produces a noticeable clinicobiochemical effect.

Indexes of fibrinolytic and proteolytic blood and urine activity in secondary pyelonephritis in children up to and after operative treatment for obstructive pyelonephritis were studied. The simulating method of hydronephrosis and secondary pyelonephritis was elaborated, changes of the tissues fibrinolytic activity of pyelourethral segment region in conditions of experiment and in operated children were studied. After the operation the conditions for urodynamics disorder occurrence are creating, in particular, lowering of activity of urine urokinase, disorder of tissues enzymatic fibrinolysis of pyelourethral segment with activation of general hemocoagulative potential, what promotes the urolythic disease and hydronephrosis occurrence and necessity for according correction.

Prostatilen was used in 1115 patients with chronic pyelonephritis and prostatitis. It is shown that prostatilen has a corrective effect on hemocoagulation and immunity disorders, restores microcirculation, suppresses inflammation in the kidney and prostate. Thus, prostatilen is a pathogenetically sound drug for treatment in urogenital inflammation while in chronic prostatitis it can be used as a basic therapy.

Objectives: Secretory leukocyte protease inhibitor (SLPI) forms an integral part of the lung's defence, by its antimicrobial activity and by its ability to neutralize serine proteases that are released by granulocytes into the inflammatory exudate. Here, we investigate in febrile patients admitted to hospital whether plasma SLPI can serve as a marker of lung infection., Methods: We prospectively determined the SLPI concentration in 152 febrile patients (median 73 [inter-quantile range (IQR): 58-82] year; 50% male) admitted to hospital because of infection of the airways (n = 44) or pneumonia (n = 108; i.e. consolidation on chest X-ray), and in 48 febrile patients (78 [IQR: 71-85] year; 52% male) admitted because of pyelonephritis, as well as afebrile age-matched controls (n = 38). In addition, erythrocyte sedimentation rate (ESR), peripheral blood leukocytes, plasma TNFalpha and IL-10, and parameters of the APACHE-II score were determined on admission., Results: In febrile patients, SLPI was significantly increased (P < 0.001) compared with afebrile controls (63 [IQR: 50-76] ng/mL): plasma SLPI (113 [IQR: 83-176] ng/mL) was highest (P < 0.005) in patients with pneumonia compared with other groups (88 [IQR: 70-118] ng/mL). Only in patients with pneumonia, bacteremia significantly increased (P < 0.01) SLPI concentrations. Using a radiological classification of pulmonary infiltrates based on their size, it was found that plasma SLPI was proportional to the extent of lung tissue involved: the median concentration increased from 95 [IQR: 74-139] ng/mL in unilateral segmental consolidation up to 271 [IQR: 180-460] ng/mL in bilateral lobar consolidations. In a multivariate analysis, the association between SLPI and extent of consolidation was about two-fold stronger than, and independent of, the association between SLPI and erythrocyte sedimentation rate, TNFalpha, and parameters of the composite APACHE-II score, such as heart rate and blood pressure, that reflect severity of illness., Conclusion: SLPI is an indicator of the presence and extent of pneumonia in febrile patients admitted to hospital. In patients with an infection with its primary source located outside the lung, plasma SLPI likely reflects the mucosal response to circulating inflammatory mediators reflecting severity of illness.