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Significance of antibody-coated bacteria in urinary sediment in experimental pyelonephritis.

The sequential appearance of antibody-coated bacteria in urinary sediment was followed in experimental pyelonephritis produced with Escherichia coli O6:K13:H1. It was possible to determine against which antigen of the organism this antibody was directed. Antibody-coated bacteria appeared by day 11 of infection, a time which coincided with the synthesis of local (intrarenal) antibody. Bacteria coated with antibody more than three days after serum antibody but four days before urinary antibody appeared. Antibody eluted from coated bacteria was directed against the O-antigen of the infecting organism but not the K-antigen. Newly synthesized intrarenal antibody and urinary antibody were directed only against O-antigen, but not against K-antigen; this finding would explain why the antibody that coated the bacteria was antibody to lipopolysaccharide. Thus, a positive test for antibody-coated bacteria indicates that a local immune response to O-antigen has occurred. It is postulated that this immune response could relate to the clinical symptomatology of acute symptomatic pyelonephritis since most patients presenting with acute pyelonephritis have bacteria coated with antibody.

Animals↗

Reflux nephropathy and chronic atrophic pyelonephritis: a review.

Chronic atrophic pyelonephritis is associated with vesicoureteric reflux in infancy. Reflux disappears during childhood in 50% of cases. It is more commonly detected in infants (49%) and children (26%) with infection than in adults (4.4%). Severe reflux may persist in adults and is usually (94%) associated with scarring. Patients with end-stage renal failure due to pyelonephritis are much younger than patients with end-stage renal failure due to other causes. The incidence of reflux according to sex is equal in infancy, but after infancy both pyelonephritic scarring and reflux are far more common in females. Infection is the likely cause of progressive scarring in females. Hypertension is associated with chronic atrophic pyelonephritis. Proteinuria is the worst prognostic feature in patients with reflux nephropathy and pyelonephritic scarring. Intrarenal reflux determines the site of scarring. The role of surgical correction of vesicoureteric reflux remains uncertain, but meticulous control of infection appears to prevent progressive scarring.

Adolescent↗

Synergism of ampicillin and gentamicin against obstructive pyelonephritis due to Escherichia coli in rats.

Rats with obstructive pyelonephritis due to Escherichia coli were treated for different intervals with ampicillin and gentamicin either alone or in combination. The combination of ampicillin and gentamicin was synergistic in vitro and significantly more effective in vivo than was either drug alone. After treatment for 10 days, the combination of ampicillin and gentamicin was the only regimen that sterilized all of the pyelonephritic kidneys. The importance of achieving sterility was illustrated by the observation that severe infection and acute pyelonephritis recurred after religation of the ureter in 12 (71%) of 17 ampicillin-treated animals that had harbored as few as 46 organisms per kidney before ligation. A synergistic combination of antibiotics rapidly sterilizes obstructed pyelonephritic kidneys. In view of the particular risk of renal infection in the presence of urinary obstruction in humans, synergistic antibiotic combinations may be useful in the treatment of obstructive pyelonephritis in humans.

Acute Disease↗

Role of suppressor cells in experimental pyelonephritis.

The effect of suppressor cells on the synthesis of antibody and development of antigen-responsive lymphocytes was studied in rabbits with pyelonephritis produced with Escherichia coli O6:K13:H1. The responsiveness of splenic lymphocytes to phytohemagglutinin (PHA), which was reduced early in infection, was restored by preincubation of cells with indomethacin. The response of lymphocytes to E. coli antigen was also suppressed early. Indomethacin increased response to PHA but did not affect response to antigen. Rabbits given indomethacin from days 1-3 of infection had a delay in suppressor cell activity until day 9, but this early inhibition had no effect on synthesis of immunoglobulin or antibody or on serum levels of IgM or IgG. Thus, activity of splenic suppressor cells in pyelonephritis can be diminished by indomethacin, an inhibitor of prostaglandin synthetase, but the suppressor cells do not appear to influence the immune response or activities of bone marrow-derived lymphocytes such as antibody formation in experimental pyelonephritis.

Animals↗

Screening and treatment of asymptomatic bacteriuria in pregnancy prevent pyelonephritis.

Although asymptomatic bacteriuria during pregnancy is associated with an increased risk of developing pyelonephritis, the effectiveness of screening programs to reduce this risk is controversial. A sharp reduction in the annual incidence of pyelonephritis (1.8% to 0.6%, P < .001) occurred after the introduction of a program to screen and treat asymptomatic bacteriuria among pregnant women followed at a large teaching hospital. The data provide retrospective and prospective evidence that screening and treatment programs for asymptomatic bacteriuria during pregnancy reduce the risk of pyelonephritis in a population with a moderate to high prevalence of bacteriuria.

Bacteria↗

Comparative efficacy of gemifloxacin in experimental models of pyelonephritis and wound infection.

Gemifloxacin (SB-265805) is a potent, novel fluoroquinolone with broad-spectrum antimicrobial activity. In this study, the efficacy of gemifloxacin was studied in experimental models of Gram-negative pyelonephritis (caused by Escherichia coli or Proteus mirabilis) and Gram-positive wound infection resulting from Streptococcus pyogenes, Staphylococcus epidermidis or Staphylococcus aureus. Gemifloxacin activity against these pathogens was compared with those of amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin, levofloxacin and tosufloxacin. Oral treatment was initiated 1 h after infection and continued once or twice daily for 3 days. Around 17 h after the end of treatment, animals were killed and the infected kidneys or the skin around the wound site were excised for the enumeration of viable bacteria. In the pyelonephritis model (either microorganism), gemifloxacin reduced bacterial numbers significantly (P < 0.01) compared with no treatment. No comparator agent had a greater effect than gemifloxacin. Notably, grepafloxacin and azithromycin were significantly less effective (P < 0.01) than gemifloxacin against E. coli pyelonephritis, and amoxycillin-clavulanate, azithromycin and trovafloxacin were inferior (P < 0.01) against P. mirabilis infection. In the S. pyogenes wound infection model, gemifloxacin, amoxycillin-clavulanate, cefuroxime and azithromycin reduced bacterial numbers significantly compared with controls (P < 0.01). Results for the comparator quinolones were not significantly different from untreated controls (P > 0.05). Gemifloxacin was also effective against staphylococcal infection, as were grepafloxacin and levofloxacin, while ciprofloxacin, trovafloxacin and tosufloxacin were significantly less effective against these pathogens than gemifloxacin (P < 0.01). No comparator agent had greater activity than gemifloxacin against S. pyogenes or S. aureus infections. These data demonstrate the potential benefit of gemifloxacin in the treatment of Gram-negative urinary tract infection and Gram-positive skin and soft tissue infection.

Animals↗

Long-term follow-up of patients presenting to adult nephrologists with chronic pyelonephritis and 'normal' renal function.

We studied the natural history, and therefore prognosis, of patients with chronic pyelonephritis presenting to adult nephrologists with a plasma or serum creatinine <90 mmol/l. From the Newcastle chronic pyelonephritis database, 255 patients with radiologically-proven disease were reviewed. Median follow-up was 95 months (95%CI 82. 3-109.3). Plasma creatinine was < or =90 micromol/l (P(Cr)< or =90 group) at presentation in 138. At presentation, hypertension, bilateral disease and proteinuria were less frequent in the P(Cr)< or =90 group (hypertension 19% vs. 32%, p<0.05; bilateral disease 25% vs. 70%, p<0.001; proteinuria 18% vs. 60%, p<0.001). With the exception of two patients, the renal prognosis of this group was excellent. Patients over the age of 18 years presenting to adult nephrologists with a diagnosis of chronic pyelonephritis and a creatinine < or =90 micromol/l can be reassured that the chances of developing end-stage renal failure in the future are very small. Most could be referred back to their general practitioner for long-term follow-up.

Adult↗

Emphysematous pyelonephritis in a nonfunctioning renal allograft of a patient undergoing hemodialysis.

A hemodialysis patient with insulin-dependent diabetes mellitus and a non-functioning renal allograft in whom fever, low blood pressure, and confusion developed is reported. She underwent extensive evaluation and allograft nephrectomy for emphysematous pyelonephritis that was diagnosed by the presence of air in the collecting system of the transplanted kidney during computerized tomography of the abdomen. In nine patients with emphysematous pyelonephritis in renal allografts reported previously, this is the first instance of emphysematous pyelonephritis in a renal allograft with coagulase-negative staphylococcus.

Coagulase↗

Tc-99m DTPA renal scintigraphy using deconvolution analysis with six functional images of the mean time to evaluate acute pyelonephritis.

In 38 children with proved P-fimbriated Escherichia coli acute pyelonephritis, Tc-99m DTPA dynamic renal scintigraphy in the zoom mode using deconvolution analysis was performed, and the results were compared with those of Tc-99m DMSA scans. From the dynamic study, six functional images of the mean time were generated. Each functional image was analyzed separately to search for focal areas of increased mean time within the kidney contour, especially over the kidney parenchyma. Time-activity curves from these areas were generated and analyzed. Tc-99m DMSA scintigraphy showed generalized or focal decreased uptake in 32 (41.8%) kidneys, and deconvolution analysis of Tc-99m DTPA scintigraphy revealed pathologic renographic curves in 58 (77.6%) kidneys. Prolonged whole-kidney and normal renal parenchymal transit times (dilatation without obstruction) were found in 38 (50%) kidneys, whereas prolonged whole-kidney and renal parenchymal transit times (dilatation with obstruction) were observed in 20 (27.6%) kidneys. Separate analysis of each of the six functional images of the mean time showed focal areas of increased mean time in the kidney parenchyma of 11 kidneys. In five cases, time-activity curves from these areas showed a sharp increase of activity on the descending part of the curve, which might reflect the return of urine from the collecting system into kidney cortex (i.e., intrarenal reflux). These results showed that in a urinary tract with acute pyelonephritis, urodynamic changes may lead to obstructive nephropathy and intrarenal reflux. Tc-99m DTPA renal scintigraphy in the zoom mode using deconvolution analysis with six functional images of the mean time has proved to be a valuable method to evaluate acute pyelonephritis, thus allowing dynamic and morphologic analysis of the urinary tract at the same time.

Child↗

Magnetic resonance imaging of experimental pyelonephritis in rabbits.

RATIONALE AND OBJECTIVES: An experimental model of acute focal pyelonephritis was developed in the New Zealand White rabbit, with initial imaging evaluation performed using high-field contrast-enhanced magnetic resonance (MR) in six animals. METHODS: The left kidney was visualized fluoroscopically after intravenous injection of iodinated contrast. A 0.1 mL mixture of agarose/Streptococcus faecalis was then injected percutaneously into the kidney at the corticomedullary junction with a 25-gauge needle. The animals were imaged at 1.5 tesla on day 5 after injection of bacteria. Breathhold T2-weighted and T1-weighted scans were acquired prior to contrast injection. Using an MR-compatible power injector, 0.3 mmol/kg gadoteridol was then administered, with both dynamic and delayed postcontrast scans obtained. The lesion was confirmed in each animal by gross and microscopic exam. RESULTS: The area of acute focal pyelonephritis was somewhat difficult to identify on precontrast scans. The lesion was mildly hyperintense on T2-weighted scans and slightly hypointense to isointense on T1-weighted scans relative to normal surrounding renal parenchyma. On early dynamic turbo-fast low-angle shot scans, the lesion could be identified due to differential tissue enhancement. Direct visualization of the lesion, with increased conspicuity relative to precontrast scans, was possible because of delayed positive enhancement at 60 seconds postcontrast. Lesion conspicuity, assessed by signal difference/noise ratio, increased from 0 +/- 5 precontrast to a peak of 12 +/- 6 at 60 seconds postcontrast (P = 0.003; n = 6). CONCLUSIONS: On dynamic contrast-enhanced MR, acute focal pyelonephritis can demonstrate transient positive contrast enhancement (using a contrast dose of 0.3 mmol/kg) relative to surrounding normal renal parenchyma. This appearance is due to hyperconcentration of the contrast agent in normal parenchyma and T2 effects. The pattern is opposite that seen in spiral computed tomography.

Acute Disease↗

Pyelonephritis in pregnancy.

Pyelonephritis, while rare in nonpregnant women, is the leading cause of hospitalization for nonobstetric indications in pregnant women. Pregnancy complications such as preterm labor and intrauterine growth retardation have been associated with pyelonephritis. Pyelonephritis can also lead to life-threatening conditions such as endotoxic shock and respiratory insufficiency. Thus the condition requires hospitalization and close follow-up in the pregnant women.

Adult↗

The importance of 99Tcm-DMSA renal scintigraphy in the follow-up of acute pyelonephritis in children: comparison with urographic data.

At present, 99Tcm-dimercaptosuccinic acid (DMSA) renal scintigraphy is the most sensitive examination for the detection of parenchymal damage during acute pyelonephritis (APN) in children. This prospective study had three aims: (1) to evaluate the medium-term evolution of the scintigraphic abnormalities, to find a prognostic criterion of scintigraphic evolution; (2) to assess the correlation between the severity of early or late scintigraphic damage and selected clinical factors; and (3) to compare the permanent scintigraphic renal scars with intravenous urography (IVU) 2 years after the acute infection. Seventy-four children (mean age 32 months), presenting with a first clinical episode of pyelonephritis and an initial scintigraphic abnormality, were included in the study. Patients with a history of urinary tract infection (UTI), uropathy other than vesico-ureteral reflux (VUR) and a relapse of acute pyelonephritis were excluded. All children underwent control scintigraphy (mean 9 months after APN) and 43 had an IVU (mean 26 months after APN). Fifty-seven children (77%) still have scintigraphic abnormalities of varying severity (7 atrophic kidneys). Initial relative DMSA uptake of less than 45% results in a worse scintigraphic prognosis. The age of the child has no bearing on the severity of the initial renal involvement or on the evolution of the scintigraphic abnormalities. The rapid introduction of antibiotics (< 12 h) significantly improves the scintigraphic prognosis (P < 0.01). The presence of reflux (n = 39) leads to more serious initial damage, but we did not find any effect on later evolution in this study, in which all reflux was low grade in nature. Among the 43 children who had an IVU, 5 showed typical urographic and scintigraphic renal scars in the corresponding region and 38 showed a normal IVU with 28 cases of scintigraphic abnormalities. A DMSA scan is more sensitive than IVU for the detection of renal scarring after a first episode of APN.

Acute Disease↗

Evolution of differential renal function after acute pyelonephritis.

(99m)Tc dimercaptosuccinic acid (DMSA) renal scans can provide accurate diagnosis of acute pyelonephritis, its sequelae (renal scars) and differential renal function (DRF). The purposes of this retrospective study were (1) to assess the relationship between DRF obtained during acute pyelonephritis and at follow-up, and (2) to elucidate the value of initial DRF in predicting subsequent renal scars. A total of 47 children were enrolled. All had both unilateral acute pyelonephritis diagnosed by initial DMSA renal scans, and follow-up DMSA renal scans. We found the correlation between initial and follow-up DRF poor (adjusted R2 = 0.396). Whether or not renal scars developed determined the follow-up DRF. Vesicoureteral reflux was significantly more common in children who developed renal scars. In addition, the higher the grade of vesicoureteral reflux, the lower the follow-up DRF and the improvement in DRF. When using a DRF of 46% as the cut-off value to predict subsequent renal scars, the sensitivity and specificity were 47.8% and 83.3%, respectively. Owing to the low sensitivity, initial DRF is not suitable for predicting the occurrence of renal scars.

Acute Disease↗

Impact of vesicoureteral reflux on the size of renal lesions after an episode of acute pyelonephritis.

PURPOSE: We determined the impact of vesicoureteral reflux (VUR) on the size of renal lesions in children after an episode of acute pyelonephritis. MATERIALS AND METHODS: A total of 161 children (mean age 2.44 years) with acute pyelonephritis were studied. All had renal lesions on dimercapto-succinic acid scintigraphy done at admission to the hospital. A second dimercapto-succinic acid scan was performed at 3 months. Voiding cystourethrography was done at 6 weeks and VUR was graded I to V. For each renal unit layouts of renal lesions were drawn, and the damage surface was calculated and reported for the total surface of the kidney. RESULTS: Mean size of acute lesions and scars increased with severity of reflux (p <0.0001), with an important overlap of individual values. Mean size of renal scars in the group of renal units with acute lesions was 5.8% +/- 8.5% in patients without VUR, 9.9% +/- 7.3% in those with grade I reflux, 7.7% +/- 11.0% in those with grade II reflux, 17.7% +/- 14.7% in those with grade III reflux and 17.4% +/- 27.7% in those with grade IV reflux (p <0.001). The size of renal lesions decreased significantly with time. The rate of regression of lesions decreased with increasing reflux. When analyzed according to 3 age groups sizes of scars increased significantly with age. CONCLUSIONS: VUR has an impact on the size of renal lesions after an episode of pyelonephritis. Children with a grade III or IV reflux are more likely to have larger renal scars. On the other hand, acute lesions of important size may develop even in the absence of VUR.

Acute Disease↗

The osmotic stress response and virulence in pyelonephritis isolates of Escherichia coli: contributions of RpoS, ProP, ProU and other systems.

Trehalose synthesis (RpoS-dependent) and betaine uptake mediated by transporters ProP and ProU contribute to the osmotolerance of Escherichia coli K-12. Pyelonephritis isolates CFT073 and HU734 were similar and diminished in osmotolerance, respectively, compared to E. coli K-12. The roles of RpoS, ProP and ProU in osmoregulation and urovirulence were assessed for these isolates. Strain HU734 expressed an RpoS variant which had low activity and a C-terminal extension. This bacterium accumulated very little trehalose and had poor stationary-phase thermotolerance. For E. coli CFT073, introduction of an rpoS deletion impaired trehalose accumulation, osmotolerance and stationary-phase thermotolerance. The rpoS defects accounted for the difference in osmotolerance between these strains in minimal medium of very high osmolality (1.4 mol kg(-1)) but not in medium of lower osmolality (0.4 mol kg(-1)). The slow growth of both pyelonephritis isolates in high-osmolality medium was stimulated by glycine betaine (GB) and deletion of proP and/or proU impaired GB uptake. An HU734 derivative lacking both proP and proU retained osmoprotective GB uptake activity that could be attributed to system BetU, which is not present in strain K-12 or CFT073. BetU transported GB (K(m), 22 microM) and proline betaine. High-osmolality human urine (0.92 mol kg(-1)) included membrane-permeant osmolyte urea (0.44 M) plus other constituents which contributed an osmolality of only approximately 0.4 mol kg(-1). Strains HU734 and CFT073 showed correspondingly low GB uptake activities after cultivation in this urine. Deletion of proP and proU slowed the growth of E. coli HU734 in this high-osmolality human urine (which contains betaines) but had little impact on its colonization of the murine urinary tract after transurethral inoculation. By contrast, deletion of rpoS, proP and proU had no effect on the very rapid growth of CFT073 in high-osmolality urine or on its experimental colonization of the murine urinary tract. RpoS-dependent gene expression is not essential for growth in human urine or colonization of the murine urinary tract. Additional osmoregulatory systems, some not present in E. coli K-12 (e.g. BetU), may facilitate growth of pyelonephritis isolates in human urine and colonization of mammalian urinary tracts. The contributions of systems ProP and ProU to urinary tract colonization cannot be definitively assessed until all such systems are identified.

Amino Acid Transport Systems↗

P-fimbriated Escherichia coli in adults with renal scarring and pyelonephritis.

The commonest organism in urinary tract infections (UTI) is Escherichia coli. Pyelonephritogenic E.coli strains possess P-fimbriae which firmly attach to uroepithelial cells by recognition of a carbohydrate structure, alpha-D-Galp-(1-4)-beta-D-Galp, which is confined within all glycosphingolipids related to the human P-blood group antigens. Several investigators have studied virulence properties of E.coli and host resistance in relation to UTI. Uroepithelial cells from children and women with recurrent UTI have an increased capacity to bind E.coli. In contrast to previous studies the present one deals with patients with renal scarring, who constitute the major risk group among patients with UTI. P-fimbriae mediated binding to uroepithelial cells was studied and the risk of recurrent UTI in patients with renal scarring was determined. Ninety per cent of the E.coli isolates from female patients with acute non-obstructive pyelonephritis in this study possess P-fimbriae (I). The fecal E.coli colonies obtained from these patients were P-fimbriated in 55% compared to 11% of the fecal E.coli colonies from healthy controls. The P-blood group distribution in 56 female patients with renal scarring and a history of febrile UTI was the same as in a control group of 39 healthy subjects (II). A history of recurrent and/or early infections did not increase the percentage of the P1 blood group phenotype. Forty-nine female patients with renal scarring were prospectively investigated for the incidence of symptomatic UTI in relation to fecal colonization with P-fimbriated E.coli (III). Fifty-three per cent of the patients had altogether 65 episodes of symptomatic UTI during the three-year follow-up (0.036 infections per month). Eight patients (16%) had nine attacks of acute pyelonephritis and 4/5 of the tested E.coli strains from these patients were P-fimbriated. No relationship was demonstrated between the presence of P-fimbriated E.coli in the fecal flora and the development of subsequent acute pyelonephritis. The binding of P-fimbriated E.coli to uroepithelial cells from 19 female patients with renal scarring was studied with the fluorescence-activated cell sorting (FACS) analysis (IV). The uroepithelial cells from the patients with renal scarring exhibited a significantly higher binding capacity (p less than 0.01) than uroepithelial cells from healthy controls. Furthermore, uroepithelial cells from the patients with renal scarring and kidney insufficiency had a higher availability of P-fimbriae receptors on their uroepithelial cells than cells obtained from patients with renal scarring and normal renal function (r = -0.75, p less than 0.001) (V).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Clinicopathological study of vesicoureteral reflux (VUR)-associated pyelonephritis in renal transplantation.

We retrospectively studied the occurrence of vesicoureteral reflux (VUR)-associated pyelonephritis using renal biopsies obtained from the transplanted kidneys, and correlated the histological changes with clinical parameters. Out of a total of 131 renal biopsies performed between 1990 and 2001 on renal transplant patients at the department of Urology of Nagasaki University Graduate School of Biomedical Sciences, 12 patients showed pyuria more than twice in a single year. Seven of these 12 patients were available for determining VUR by voiding cystourethrography (VCUG). Cystoureterography demonstrated VUR in three of seven studied patients with pyuria. A histopathological examination revealed dilatation of both proximal and distal tubules in renal biopsies of transplant patients with VUR, compared to renal biopsies of transplant patients without VUR, or non-transplanted patients with thin membrane disease. One of the patients with VUR showed advanced features of chronic pyelonephritis in four consecutive biopsies at different time points, suggesting a late stage of reflux nephropathy in the transplanted kidney. We conclude from our study that the occurrence of VUR-related pyelonephritis may be one of the important long-term complications in the survival of renal allografts.

Adult↗

Case of emphysematous pyelonephritis in a renal allograft.

Emphysematous pyelonephritis is a rare, but serious complication after renal transplantation. This is a case report of a 49-yr-old female who had a renal transplant for diabetic nephropathy. She presented to ER with about 1 wk history of right lower abdominal pain and fever 15 months after the transplant. She had gross hematuria and mental status changes just prior to presentation. A computed tomography (CT) scan of the abdomen showed extensive retroperitoneal and extraperitoneal air dissecting from the transplanted kidney in the right lower quadrant to the level of the mediastinum. There was air in the urinary bladder. These findings were highly suggestive of extensive emphysematous pyelonephritis. The patient was taken to the operating room emergently and underwent a transplant nephrectomy. Blood culture and urine culture were subsequently positive for Salmonella (serogroup O 6, 8 or C2). Initial blood culture also yielded Enterobacter cloacae. The patient was treated with imipenem, cefepime, flagyl, and diflucan empirically: this was later changed to complete a 6-wk course of ciprofloxacin upon discharge. Her hospital course was complicated by a urinary leak; she was discharged to home on day 21. This is the 12th reported case of emphysematous pyelonephritis occurred in a renal transplant recipient.

Emphysema↗