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PubMed2006

Antibiotic treatment for acute 'uncomplicated' or 'primary' pyelonephritis: a systematic, 'semantic revision'.

The definition of acute pyelonephritis is controversial. There are two contrasting approaches: (1) acute pyelonephritis is a severe infectious disease involving the kidney parenchyma, and specific imaging techniques are required for diagnosis; (2) acute pyelonephritis is a urinary tract infection, and diagnosis and therapy follow simplified clinical and laboratory pathways. In this study, recent randomized controlled trials (RCTs) were systematically reviewed and the diagnostic and therapeutic approaches to acute 'uncomplicated' pyelonephritis were analysed. Medline, Embase, Cochrane Central Register of Controlled Trials (CCTR) and Chinal were searched employing Mesh, Emtree and free terms on 'pyelonephritis'. Limits included human, period (1995-2004), and trials-reviews (where available). In total, 904 references and 175 full-text were retrieved; 29 were pertinent RCTs. Seven RCTs were added from reference lists (indexed on urinary tract infections). Imaging examinations were performed in 11 of 14 studies on children (diagnostic requisite in two) and in two studies on adults; scarring was not analysed in adults. Clinical definitions varied widely (fever >37.8 to >39 degrees C, culture titres 10(4) >10(5)). Studies on adults were limited to short-term end-points (microbiological sterilization, clinical improvement). Duration of therapy was 4-20 days. The trend was towards shorter periods of therapy, mainly on an outpatient basis; intravenous therapy, if performed, was usually limited to the first 1-3 days. For acute uncomplicated pyelonephritis, the tendency is towards 2 weeks of mainly oral antibiotic therapy. However, the recent literature on adults does not discriminate among different upper urinary tract infections nor does it provide data on renal scarring. While cost constraints point towards short-term therapies, further studies are needed to assess the prevalence and long-term effect of kidney scars.

Acute Disease↗
PubMed1987

Pyelonephritis following pediatric renal transplant: increased incidence with vesicoureteral reflux.

The association between pyelonephritis and vesicoureteral reflux (VUR) following pediatric renal transplantation is unclear. To understand the relationship of vesicoureteral reflux with urinary tract infection (UTI) and pyelonephritis, 67 patients were evaluated for reflux and pyelonephritis. Sixty-seven pediatric patients, aged 2 to 18 (39 males and 28 females) underwent renal transplantation. Beginning in 1982, all patients underwent voiding cystourethrography or radionuclide voiding studies 1 to 3 months postoperatively to assess the incidence of VUR. Techniques of ureteroneocystostomy (UNC) included the Leadbetter-Politano (L-p) in 39 cases, and two different modifications of the LICH (herein called LICH-1 and LICH-2) in 30 cases. Urinary cultures were performed routinely. Pyelonephritis was considered present in any patient with UTI and increased serum creatinine or fever greater than 38.5. VUR occurred in 36% of patients; highest in LICH-1 (79%), intermediate in L-P (22%), and lowest in LICH-2 (9%). VUR was not statistically significantly higher in females (43%) v males (31%). UTI occurred in 37% of patients. The difference in incidence between females (54%) and males (26%) was significant (P less than .05). The frequency of UTI in patients with VUR was 46% v 33% in patients without reflux (NS). However, pyelonephritis that occurred in 16% of cases overall was present in 82% of UTIs in patients with reflux v 14% of UTIs in patient without reflux (P less than .01). Pyelonephritis is significantly increased in pediatric renal transplant patients with UTI was have VUR. A nonrefluxing UNC is advocated in all patients. All renal transplant patients should have routine monitoring of urinary cultures and should be evaluated of VUR posttransplant.

Adolescent↗
PubMed1998

Predictors of outcome in emphysematous pyelonephritis.

PURPOSE: We identified and quantified prognostic factors for emphysematous pyelonephritis. MATERIALS AND METHODS: The clinical information, laboratory data and radiological findings from 38 patients with emphysematous pyelonephritis were retrospectively analyzed. RESULTS: There were no significant differences between the nonsurvivor and survivor groups with respect to age, gender, diabetes mellitus history, presence of bacteremia, identity of infecting organisms, blood glucose level, leukocyte count, urinary white blood count, presence or absence of urinary tract obstruction or urolithiasis, and modes of treatment. There were significant differences between the nonsurvivor and survivor groups, however, with respect to platelet count (84,300 +/- 119,500 versus 220,400 +/- 161,800/mm.3, p = 0.001), serum creatinine level (3.61 +/- 1.25 versus 2.19 +/- 1.32 mg./dl., p = 0.003) and urinary red blood counts (56.47 +/- 41.86 versus 27.65 +/- 36.14, p = 0.028). Patients with radiological type I emphysematous pyelonephritis were significantly more likely to die than those with type II (69 versus 18%, p = 0.002). CONCLUSIONS: Serum creatinine level is the most reliable predictor of outcome in patients with emphysematous pyelonephritis. By calculating likelihood ratios, patients with creatinine levels greater than 1.4 mg./dl. and platelet counts 60,000/mm.3 or less were at high risk. The posttest probability of death increased from 69 and 18% to 92 and 53% for type I and II emphysematous pyelonephritis, respectively. Patients with creatinine levels 1.4 mg./dl. or less and platelet counts greater than 60,000/mm.3 were at much lower risk. Posttest mortality risk in these patients dropped from 69 and 18% to 27 and 4% for type I and II emphysematous pyelonephritis, respectively.

Adult↗
PubMed1992

Renal scarring following reflux and nonreflux pyelonephritis in children: evaluation with 99mtechnetium-dimercaptosuccinic acid scintigraphy.

99mTechnetium dimercaptosuccinic acid (DMSA) scintigraphy is the imaging modality of choice for the detection of acute pyelonephritis and chronic renal scarring in children. Using the DMSA scan we prospectively evaluated renal scarring after reflux and nonreflux pyelonephritis in children. The study population consisted of 33 patients with acute pyelonephritis documented by a DMSA renal scan at infection. The children were evaluated for renal scarring with a followup DMSA scan 4 to 42 months (mean 10.7 months) after the acute infection. All new scarring on followup DMSA scans occurred at sites corresponding exactly to areas of acute inflammation on the initial DMSA scan. Therefore, only those kidneys with acute changes on the initial scan were subsequently analyzed. Of 38 kidneys new or progressive scarring developed in 16 (42%), including 6 of 15 (40%) with associated vesicoureteral reflux and 10 of 23 (43%) without demonstrable reflux. New renal scarring developed in 6 of the 7 kidneys (86%) associated with a neuropathic bladder or posterior urethral valves. In contrast, new scarring developed in only 10 of 31 kidneys (32%) associated with a normal bladder (p = 0.028). Excluding the kidneys associated with a neuropathic bladder or posterior urethral valves, new renal scarring developed in 3 of 12 (25%) with primary reflux, compared with 7 of 19 (37%) without vesicoureteral reflux. Except for the white blood count and the species of infecting bacteria, no other statistically significant differences could be found between those cases in which scars did or did not develop. We conclude that acquired renal scarring only occurs at sites corresponding to previous areas of acute pyelonephritis, the acute parenchymal inflammatory changes of acute pyelonephritis are reversible and do not lead to new renal scarring in the majority of cases, and once acute pyelonephritis has occurred ultimate renal scarring is independent of the presence or absence of vesicoureteral reflux.

Adolescent↗
PubMed1980

Post-transplantation pyelonephritis: factors producing low patient and transplant morbidity.

A retrospective study of 1,100 consecutive renal transplantations done on 959 patients revealed postoperative pyelonephritis in 15 patients, 14 of whom were women. Sixteen of the 20 episodes of pyelonephritis were caused by Escherichia coli and only 4 episodes occurred within the first year after transplantation, thus revealing the crucial differentiation from a rejection episode. When the etiology of the original renal failure was pyelonephritis the incidence of pyelonephritis in the transplanted kidneys was high. This high incidence also was true for cases associated with post-transplantation urological complications. When the etiology of renal failure was diabetes or polycystic renal disease, or when urologic abnormalities pre-existed the incidence of pyelonephritis was low. No transplant or patient loss was caused by post-transplantation pyelonephritis, probably because of prompt, correct diagnosis and a low urological complication rate.

Adult↗
PubMed1998

Acute childhood pyelonephritis: predictive value of positive sonographic findings in regard to later parenchymal scarring.

RATIONALE AND OBJECTIVES: The authors evaluated the importance of positive sonographic findings in acute childhood pyelonephritis. MATERIALS AND METHODS: A total of 290 children (91 boys, 199 girls, aged 4 days to 15 years [median, 394 days]) with clinically suspected acute pyelonephritis underwent initial renal gray-scale ultrasound (US) and dimercaptosuccinate scintigraphic examination within 3 days of onset. A total of 173 patients underwent color or energy US examination. One hundred fifteen children with normal scintigraphic or pathologic findings (other than acute pyelonephritis) were excluded from further study; 170 patients with abnormal scintigraphic findings underwent follow-up scintigraphic scanning 60-90 days later. RESULTS: When pathologic structures other than acute pyelonephritis were not considered, the diagnostic value of gray-scale US was poor, with a sensitivity of 45.5%, a specificity of 86.6%, a positive predictive value of 88.8%, and a negative predictive value of only 40.6%. In regard to future renal scarring, gray-scale US had a positive predictive value of 67.7%, a negative predictive value of 40%, and a likelihood ratio of 1.16. Abnormal Doppler findings helped predict future scarring with a positive predictive value of 85.7%, a negative predictive value of 37.2%, a very low sensitivity of 26.9%, a high specificity of 90.6%, and a likelihood ratio of 2.87. CONCLUSION: Positive US Doppler findings in children with clinically suspected acute pyelonephritis indicate the need for immediate treatment. A positive initial gray-scale US examination does not predict future renal scarring, but a positive Doppler examination indicates a high probability of scarring. Negative gray-scale or Doppler US does not exclude a diagnosis of acute pyelonephritis and it cannot predict an absence of future scarring.

Acute Disease↗
PubMed1962

The role of immunity in the pathogenesis of experimental hematogenous pyelonephritis.

Hematogenous pyelonephritis was produced in rats utilizing multiple strains of Escherichia coli, a strain of Klebsiella pneumoniae, and a strain of Proteus mirabilis. Three patterns of hematogenous pyelonephritis occurred which represent an interrelationship between an immune response to the infecting bacteria and the development of obstructive uropathy as a consequence of infection. First, the course of pyelonephritis due to strains of Escherichia coli was acute, self-limited, and associated with the development of circulating agglutinins. Following healing, this pattern of infection was associated with acquired resistance to reinfection with the same bacterial strain. Second, the course of pyelonephritis due to a strain of Klebsiella pneumoniae type C was chronic. This infection was not associated with the production of circulating agglutinins against encapsulated strains. Acquired resistance to reinfection by the homotypic strain could not be demonstrated following eradication of infection but was produced by the passive transfer of concentrated antiserum. Third, pyelonephritis due to Proteus mirabilis was associated with circulating agglutinins and resistance to reinfection with the same organism following eradication of infection, yet the course was chronic. The chronicity appeared to be the consequence of obstructive uropathy resulting from calculi which developed during the course of the infection. Resistance to reinfection was demonstrated in infections with strains of E. coli and P. mirabilis. The resistance is associated with specific immunity as demonstrated by the observation that: (a) it is type-specific, (b) it is of at least 3 months' duration, and (c) it can be passively transferred by means of rabbit antiserum. Since K. pneumoniae failed to evoke capsular antibodies in the rat, resistance to infection with K. pneumoniae was produced only by means of passively transferred concentrated rabbit antiserum and not by prior infection. Immunity can be demonstrated to have a significant role in the pathogenesis of experimental hematogenous pyelonephritis only in the absence of obstructive uropathy.

Animals↗
PubMed1996

Hospitalization for acute pyelonephritis in Manitoba, Canada, during the period from 1989 to 1992; impact of diabetes, pregnancy, and aboriginal origin.

Population-based rates of hospitalization for acute pyelonephritis were estimated over 3 years with use of provincial administrative data on health care. Retrospective review of records of ICD9-CM discharge codes of pyelonephritis and urinary infection was performed in two acute care institutions to validate the discharge diagnosis; 80% of patients with a discharge diagnosis of pyelonephritis and 7% to 20% of patients with a discharge diagnosis of urinary infection met clinical criteria for admission for acute pyelonephritis. Mean rates of hospitalization +/- SD for acute pyelonephritis were 10.86 +/- 0.51 per 10,000 population among women and 3.32 +/- 0.27 per 10,000 population among men. From 18% to 31% of hospitalized women aged 20-39 years pregnant; 36% of 797 hospitalized women and 21% of 402 hospitalized men 40 years of age or older were diabetic. The hospitalization rates among Native American women with treaty status were five to 20 times greater than those among other women, which was partially attributable to a significantly greater frequency of pregnancy and diabetes in the former women. Hospitalization for acute pyelonephritis is common, and pregnancy and diabetes contribute substantially to hospitalization rates. The increased hospitalization rate among Native American women with treaty status is not fully explained by pregnancy or diabetes.

Acute Disease↗
PubMed2006

Gestational pyelonephritis as an indicator of the quality of ambulatory maternal health care services.

OBJECTIVE: Inpatient conditions that might be avoided through improved outpatient services are called Ambulatory Care Sensitive Indicators, and they include pyelonephritis in nonpregnant adults. No such indicators have been developed for pregnant women. We examine whether hospital-specific rates of gestational pyelonephritis may serve as a measure of the quality of ambulatory maternal care. METHODS: The California Department of Health Services provided an administrative data set linking maternal and newborn delivery records for 1997 with antepartum hospital admissions. We created a "low-risk" study population by largely excluding women with maternal, fetal, and placental morbidities and those with no first-trimester prenatal care. We generated hospital-specific infection rates using a Bayesian hierarchical logistic regression model. RESULTS: We identified 280,816 low-risk women, of whom 1,853 (0.66%) had at least 1 inpatient admission for gestational pyelonephritis. The model suggested only 2 risk factors: MediCal as a payer (odds ratio 1.60, 95% confidence interval 1.46-1.80 compared with all other payers), and African-American race (odds ratio 1.24, 95% confidence interval 1.10-1.41 compared with white race). Women with pyelonephritis were more than twice as likely to deliver preterm. Adjusted rates of gestational pyelonephritis for the 291 hospitals in the sample ranged from 0.22% to 2.64%. CONCLUSION: These findings suggest that because of its preventability, its consequent related morbidity, and the variation in hospital-specific rates, gestational pyelonephritis meets both clinical and technical requirements as a quality indicator for ambulatory maternal care. The use of such rates would provide an opportunity for hospitals to improve patient outcomes through partnership with obstetricians in the management of women at risk. LEVEL OF EVIDENCE: II-3.

California↗
PubMed1996

In vivo efficacies of levofloxacin and ciprofloxacin in acute murine hematogenous pyelonephritis induced by methicillin-susceptible and-resistant Staphylococcus aureus strains.

Levofloxacin, the active L-isomer of ofloxacin, has demonstrated strong activity against Staphylococcus aureus both in vitro and in vivo. In a murine model of hematogenous pyelonephritis, the in vivo efficacies of levofloxacin and ciprofloxacin were evaluated against two methicillin-susceptible and two methicillin-resistant S. aureus strains. All four isolates had virtually identical susceptibilities to levofloxacin and ciprofloxacin. Pyelonephritis was induced in carrageenan-primed mice by an intravenous injection of 0.5 ml of 10(7) CFU of methicillin-susceptible S. aureus isolates per ml or 10(8) CFU of methicillin-resistant S. aureus isolates per ml. At 1 h postinfection, the mice were treated orally with levofloxacin or ciprofloxacin once a day or twice a day (total daily dose of 20 to 160 mg/kg of body weight) for 4 days. Mice were euthanized 24 h after the final treatment, and the kidneys were excised and weighed. The kidneys were prepared for histological examination or were homogenized to determine the numbers of CFU per gram of tissue quantitatively. The reduction in the mean log10 number of CFU per gram as a function of total daily dose was recorded. A dose-response analysis showed that levofloxacin was superior to ciprofloxacin for all four isolates at any dose or regimen tested, independent of the methicillin susceptibility of the isolates. By using an inverse prediction technique, the equivalent effective doses of levofloxacin (once a day) were less than those of ciprofloxacin (twice a day) by 5.2 and 3.2 times, respectively, for methicillin-susceptible S. aureus 9039 and 3087. For methicillin-resistant S. aureus 667 and 2878, the equivalent effective doses of levofloxacin (once a day) were less than those of ciprofloxacin (twice a day) by 4.1 and 6.4 times, respectively. In a separate study, histological examination of all infected, untreated mice showed moderate to marked hematogenous pyelonephritis. Levofloxacin-treated mice (40 mg/kg once a day) showed no evidence of pyelonephritis in the kidneys, whereas the kidneys of mice treated with the same dose of ciprofloxacin showed only a reduction in the severity of the lesions. Treatment with ciprofloxacin (80 mg/kg twice a day) demonstrated a histology comparable to that of treatment with levofloxacin (40 mg/kg once a day). Levofloxacin (40 mg/kg once a day) reduced the log10 numbers of CFU per gram by 5 log10; however, ciprofloxacin (80 mg/kg twice a day) reduced the numbers of CFU per gram by only 3 log10. In the present murine model of pyelonephritis, levofloxacin was superior to ciprofloxacin in preventing pyelonephritis and eradicating S. aureus.

Acute Disease↗
PubMed1989

Relationship between neutrophil-mediated oxidative injury during acute experimental pyelonephritis and chronic renal scarring.

Previous experiments with rats have suggested that pyelonephritic scarring after acute ascending Escherichia coli pyelonephritis partly results from excessive polymorphonuclear leukocyte (PMN) infiltration and activation in the kidney parenchyma. We have studied the role of PMN oxidative metabolism in generating tissue injury during acute pyelonephritis. Rats with acute pyelonephritis were treated with dapsone (25 mg/kg twice daily for 3 days), a compound known to prevent PMN oxidant damage. In vitro, levels of dapsone easily achieved in vivo inhibited myeloperoxidase (MPO)-mediated reactions involving the oxidation of halides to reactive cytotoxic hypohalites (such as MPO-mediated iodination and luminol-enhanced chemiluminescence). In contrast, dapsone had no effect on superoxide production, lysosomal enzyme release, or bacterial killing by activated PMN. In vivo, dapsone treatment had no significant effect on acute pyelonephritis with respect to (i) bacterial counts, (ii) inflammatory swelling, and (iii) PMN infiltration. However, dapsone-treated animals sacrificed 2 months after acute pyelonephritis had a 65% reduction of renal scars when compared with controls. Since dapsone had no antibacterial effect, this protection is compatible with the hypothesis that dapsone prevented oxidant-generated tissue injury due to the extracellular release of the MPO system by activated PMN during acute suppurative pyelonephritis.

Acute Disease↗
PubMed2002

Differences in virulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men.

Differences in the presence of nine urovirulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men have been studied. Hemolysin and necrotizing factor type 1 occur significantly more frequently among isolates causing prostatitis than among those causing cystitis (P < 0.0001) or pyelonephritis (P < 0.005). Moreover, the papGIII gene occurred more frequently in E. coli isolates associated with prostatitis (27%) than in those associated with pyelonephritis (9%) (P < 0.05). Genes encoding aerobactin and PapC occurred significantly less frequently in isolates causing cystitis than in those causing prostatitis (P < 0.01 and P < 0.0001, respectively) and pyelonephritis (P < 0.01 and P < 0.0001, respectively). No differences in the presence of Sat or type 1 fimbriae were found. Finally, AAFII and Bfp fimbriae are no longer considered uropathogenic virulence factors since they were not found in any of the strains analyzed. Overall, the results showed that clinical isolates producing prostatitis need greater virulence than isolates producing pyelonephritis in women or, in particular, cystitis in women (P < 0.05). Overall, the results suggest that clinical isolates producing prostatitis are more virulent that those producing pyelonephritis or cystitis in women.

Cystitis↗
PubMed1978

Mycoplasmas in human pyelonephritis: demonstration of antibodies in serum and urine.

This study was carried out to elucidate by serological examination the etiological significance of mycoplasmas isolated from the upper urinary tract of patients with pyelonephritis. The occurrence of antibodies in patients with acute pyelonephritis, chronic pyelonephritis with or without exacerbation, or noninfectious urinary tract disease was compared by the indirect hemagglutination method. Antibody response was demonstrated significantly more often in patients yielding growth of Mycoplasma hominis from the upper urinary tract than in patients not yielding growth. Antibodies against M. hominis were demonstrated in ureteric and bladder urine from three patients with acute pyelonephritis and from one patient with exacerbation of chronic pyelonephritis. M. hominis was isolated from the upper urinary tract of all four patients. Urine antibodies could not be demonstrated in any other cases. Thus, it seems highly possible that M. hominis may play a role in pyelonephritis of humans. The investigations did not disclose a similar role for Ureaplasma urealyticum.

Acute Disease↗
PubMed1998

Combined use of urinary alpha1-microglobulin and 99mTc DMSA scintigraphy in the diagnosis and follow-up of acute pyelonephritis and cystitis in children.

OBJECTIVES: In the absence of specific symptomatology in children and neurogenic bladder disease patients, the early diagnosis of acute pyelonephritis is a challenge. The aim of the present study was to determine if dimercaptosuccinic acid (DMSA) lesion-positive (acute pyelonephritis) patients have elevated urinary alpha1-microglobulin (alpha1-MG) excretion (no false negatives) and if DMSA lesion-negative (cystitis) patients have normal urinary alpha1-MG excretion (no false positives). METHODS: A selected population of 62 children above 3 months of age with a proven urinary tract infection were administered a DMSA scan. A control scan was performed after the acute phase of the illness, and the diagnosis of pyelonephritis (n = 44) was made retrospectively. The urinary alpha1-MG was determined by immunonephelometry. RESULTS: The urinary alpha1-MG-creatinine ratio was highly sensitive (98%) and specific (100%) and correlated with the DMSA scintigraphy images. Only 1 of the 44 patients with pyelonephritis and all of the cystitis patients (n = 18) had a normal urinary alpha1-MG (<10 mg/g). The drop in absolute DMSA uptake correlated significantly (r = 0. 758, p < 0.001) with the urinary alpha1-MG-creatinine ratio. The urinary alpha1-MG-creatinine ratio was significantly higher (p < 0. 02) in bilateral than in unilateral pyelonephritis. CONCLUSION: DMSA lesion-positive (acute pyelonephritis) patients have elevated urinary alpha1-MG excretion and DMSA lesion-negative (cystitis) patients have normal urinary alpha1-MG excretion.

Acute Disease↗
PubMed1994

Interleukin-6 and interleukin-8 in serum and urine in patients with acute pyelonephritis in relation to bacterial-virulence-associated traits and renal function.

Urine and serum concentrations of interleukin (IL)-6 and IL-8 were determined in 43 women with acute pyelonephritis caused by Escherichia coli. Urine and serum samples were also collected 2 weeks after the infection and during a subsequent episode of cystitis (n = 8) or asymptomatic bacteriuria (n = 8). Concentrations of IL-6 and IL-8 were related to the expression of 5 virulence markers of E. coli and glomerular filtration rate (GFR) after pyelonephritis. Patients with acute pyelonephritis had elevated urine and serum IL-6 and IL-8 levels as compared to 37 healthy women (IL-6: p < 0.001 in both cases, and IL-8: p < 0.001 in both cases). Patients infected with E. coli producing hemolysin and/or cytotoxic necrotizing factor (CNF) had significantly higher IL-6 levels in serum during acute pyelonephritis as compared to patients infected with strains without the ability to produce these factors (p = 0.0025 and p = 0.0154, respectively). Patients who had high concentrations of IL-8 in urine during acute pyelonephritis had lower GFR at follow-up as compared to patients with lower levels of IL-8 in urine (r = -0.48, p = 0.0123). In conclusion, acute pyelonephritis is accompanied by elevated urinary and serum IL-6 and IL-8 levels. Bacteria producing hemolysin and CNF seem to induce higher concentrations of IL-6 in serum. The secretion of IL-8 from renal cells may participate in the initiation and maintenance of renal inflammation which in turn may influence renal function.

Acute Disease↗
PubMed1978

Prevention of chronic experimental pyelonephritis by suppression of acute suppuration.

In order to evaluate the importance of suppuration, persistent infection, and scar formation in the evolution of Escherichia coli chronic pyelonephritis, we treated rats with different antibiotic regimens at different stages of the disease. The results show that (a) if acute suppurative pyelonephritis is aborted with early antibiotic therapy, chronic pyelonephritis is prevented; (b) chronic pyelonephritis can develop even after eradication of infection if acute suppuration persists beyond 3 days; (c) persistent infection does not lead to chronic pyelonephritis, if the acute suppuration is suppressed; and (d) residual infection, antigen-load, antibody, and(or) cell-dependent autoimmune processes did not play a significant role. We interpret these results as evidence that the pathologic entity recognized as chronic pyelonephritis results from kidney damage, scarring and shrinkage secondary to acute suppuration.

Acute Disease↗
PubMed2003

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in acute pyelonephritis and renal scarring.

The aim of the present study was to elucidate the role of matrix metalloproteinase-9 (MMP-9), and its main inhibitor tissue inhibitor of metalloproteinases-1 (TIMP-1), in acute pyelonephritis and the process of renal scarring. Urine samples from 40 children with acute pyelonephritis, 16 children at 6-wk follow-up and 15 children with nonrenal fever were analyzed using ELISA. MMP-9 and TIMP-1 levels were compared with the outcome of pyelonephritis as measured by renal static scintigraphy. A mouse model of acute ascending pyelonephritis was used to localize the sites of production and the kinetics of MMP-9 and TIMP-1 using immunohistochemistry and ELISA. Human renal epithelial A498 cells, primary mesangial cells and monocytic THP-1 cells were stimulated by Escherichia coli. MMP-9 and TIMP-1 mRNA was analyzed by reverse transcription-PCR (RT-PCR) and protein production by ELISA. We demonstrate a significant increase of MMP-9 and TIMP-1 in the urine of children with acute pyelonephritis. Both proteins were produced mainly by leukocytes, and TIMP-1 also by resident kidney cells. Cells reacted differently after stimulation by bacteria. In mesangial cells and monocytes a decreased constitutive TIMP-1 production was found, which was in contrast to epithelial cells. Out of 40 children with pyelonephritis, 23 had higher urinary TIMP-1 than MMP-9 levels. These children had significantly more severe changes in both acute and follow-up scintigraphy scans indicating higher degree of acute tissue damage and renal scarring. Thus, our findings suggest an association between TIMP-1 and the process of renal scarring.

Acute Disease↗
PubMed2004

Procalcitonin: a marker of severity of acute pyelonephritis among children.

OBJECTIVE: Febrile urinary tract infection (UTI) is a common problem among children. The diagnosis and management of acute pyelonephritis is a challenge, particularly during infancy. The distinction between acute pyelonephritis and UTI without renal involvement is very important, because renal infection may cause parenchymal scarring and thus requires more aggressive investigation and follow-up monitoring. However, this distinction is not easy among children, because common clinical findings and laboratory parameters are nonspecific, especially among young children. In an attempt to differentiate acute pyelonephritis from febrile UTI without renal lesions in a group of 100 children, we measured serum levels of procalcitonin (PCT), a new marker of infection. The objective of the study was to determine the accuracy of PCT measurements, compared with C-reactive protein (CRP) measurements, in diagnosing acute renal involvement during febrile UTI and in predicting subsequent scars, as assessed with 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy. DESIGN: Serum CRP levels, erythrocyte sedimentation rates, leukocyte counts, and PCT levels were measured for 100 children, 1 month to 13 years of age, admitted for suspected febrile UTI (first episode). Renal parenchymal involvement was evaluated with DMSA scintigraphy within 5 days after admission. The DMSA study was repeated 6 months later if the initial results were abnormal. RESULTS: The mean PCT level was significantly higher in acute pyelonephritis than in UTI without renal lesions (4.48 +/- 5.84 ng/mL vs 0.44 +/- 0.30 ng/mL). In these 2 groups, the mean CRP levels were 106 +/- 68.8 mg/L and 36.4 +/- 26 mg/L, mean erythrocyte sedimentation rates were 79.1 +/- 33 mm/hour and 58.5 +/- 33 mm/hour, and leukocyte counts were 18 492 +/- 6839 cells/mm3 and 16 741 +/- 5302 cells/mm3, respectively. For the prediction of acute pyelonephritis, the sensitivity and specificity of PCT measurements were 83.3% and 93.6%, respectively; CRP measurements had a sensitivity of 94.4% but a specificity of only 31.9%. Positive and negative predictive values for prediction of renal involvement with PCT measurements were 93.7% and 83% and those with CRP measurements were 61.4% and 83.3%, respectively. When inflammatory markers were correlated with the severity of the renal lesions, as assessed with DMSA scintigraphy, a highly significant correlation with both PCT and CRP levels was found. However, when the 2 parameters were correlated with renal scarring in follow-up scans, a significant positive association was found only for PCT levels. CONCLUSIONS: Serum PCT levels may be a sensitive and specific measure for early diagnosis of acute pyelonephritis and determination of the severity of renal parenchymal involvement. Therefore, this measurement could be useful for the treatment of children with febrile UTIs, allowing prediction of patients at risk of permanent parenchymal renal lesions.

Acute Disease↗