Urine interleukin-6 and interleukin-8 in children with acute pyelonephritis, in relation to DMSA scintigraphy in the acute phase and at 1-year follow-up

Tullus, Kjell; Fituri, Omar; Linné, Tommy; Escobar-Billing, Ruby; Wikstad, I.; Karlsson, Anders; Burman, Lars; Wretlind, Bengt; Brauner, Annelie

doi:10.1007/bf02015016

Cited by 53 publications

(34 citation statements)

References 22 publications

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“…The development of scars in early life, particularly in patients with VUR, has been correlated with the development of hypertension, pre-eclampsia, renal insufficiency, and end-stage renal disease. Tullus et al showed that the initial IL-6 level in urine of children with pyelonephritis correlated with DMSA uptake defects in the acute phase as well as 1 year later (35). These data suggest that modulating the inflammatory response in patients with UTI should decrease the development of renal scars and the sequelae associated with them.…”

Section: Discussionmentioning

confidence: 98%

Cytokine Profiles of Pediatric Patients Treated with Antibiotics for Pyelonephritis: Potential Therapeutic Impact

Kassir¹,

Vargas-Shiraishi²,

Zaldivar

et al. 2001

Clin Diagn Lab Immunol

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Urinary tract infections are common in infants and children. Pyelonephritis may result in serious complications, such as renal scarring, hypertension, and renal failure. Identification of the timing of release of inflammatory cytokines in relation to pyelonephritis and its treatment is essential for designing interventions that would minimize tissue damage. To this end, we measured urinary cytokine concentrations of interleukin-1␤ (IL-1␤), IL-6, and IL-8 in infants and children with pyelonephritis and in healthy children. Children that presented to our institution with presumed urinary tract infection were given the diagnosis of pyelonephritis if they had a positive urine culture, pyuria, and one or more of the following indicators of systemic involvement: fever, elevated peripheral white blood cell count, or elevated C-reactive protein. Urine samples were obtained at the time of presentation prior to the administration of antibiotics, immediately after completion of the first dose of antibiotics, and at follow up 12 to 24 h after presentation. IL-1␤, IL-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assay. Creatinine concentrations were also determined, and cytokine/creatinine ratios were calculated to standardize samples. Differences between preantibiotic and follow-up cytokine/creatinine ratios were significant for IL-1␤, IL-6, and IL-8 (P < 0.01). Differences between preantibiotic and control cytokine/creatinine ratios were also significant for IL-1␤, IL-6, and IL-8 (P < 0.01). Our study revealed that the urinary tract cytokine response to infection is intense but dissipates shortly after the initiation of antibiotic treatment. This suggests that renal damage due to inflammation begins early in infection, underscoring the need for rapid diagnosis and intervention.

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Section: Discussionmentioning

confidence: 98%

Cytokine Profiles of Pediatric Patients Treated with Antibiotics for Pyelonephritis: Potential Therapeutic Impact

Kassir¹,

Vargas-Shiraishi²,

Zaldivar

et al. 2001

Clin Diagn Lab Immunol

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“…Normal uptake in a segment was given the value 0, and decreased uptake was graded 1-3. From the size and degree of a defect in DMSA uptake, a DMSA score was calculated (20).…”

Section: Patientsmentioning

confidence: 99%

Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinases-1 in Acute Pyelonephritis and Renal Scarring

et al. 2003

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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. Interstitial fibrosis is the final common end-point of progressive renal diseases. Despite its clinical significance, the mechanisms of scar formation in the kidney are still not fully understood. Generally, it is thought that the renal fibrogenesis is induced by the release of chemokines and growth factors by a number of resident cells. Their concentration gradient results in an influx of leukocytes and an increase in the number of interstitial fibroblasts. The induction phase is followed by an increased matrix production and reduced matrix degradation, which add up to a deposition of extracellular matrix (ECM) components (1). However, ECM component deposition does not seem to be the only mechanism in the pathogenesis of scarring. After direct inoculation of Escherichia coli into the kidneys of rats, contraction and collapse of the tubulointerstitial parenchyma had a greater influence than new collagen production on final fibrosis (2). In line with that, we have previously shown that mouse kidneys after experimental acute pyelonephritis were smaller compared with those from uninfected animals (3). Likewise, it seems that the end-stage kidney is rather shrunken, not enlarged or full of collagen (4).The current hypothesis suggests that the normal remodeling and healing is a result of the balance between ECM protein synthesis and degradation (5). Out of a number of matrixdegrading enzymes, gelatinases, matrix metallopro...

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“…Tullus (24) ve Krzemiẻn (21) çalışmalarında, DMSA'da skarı olanların idrar IL-8 düzeyinin olmayanlardan farklı olmadığını bildirilmiştir. Gökçe ve ark.…”

Section: Discussionunclassified

Urine levels of interleukin-8 as diagnostic marker of acute pyelonephritis in children

Tanınmış¹,

Sönmez²,

Yılmaz³

2016

Terh

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ÖZAmaç: İdrar yolu enfeksiyonu çocuklarda yaygın görülen enfeksiyon hastalıklarından olup, hala ülkemizde kronik böbrek hastalığına neden olan hastalıkların ilk sıraların-da yer almaktadır. Bakteriyel enfeksiyona yanıtta, inflamatuvar sitokinlerden interlökin-8 önemli rol alır. Bu çalışmanın amacı, idrar yolu enfeksiyonu tanısı ve lokalizasyonunu saptamada idrar interlökin-8 düzeyinin etkisini değerlendirmektir. Yöntemler: Çalışmaya idrar yolu enfeksiyonu tanılı, 1 ay -15 yaş arası, 82 çocuk ve 49 sağlıklı çocuk alındı. Hastalar Jodal'ın idrar yolu enfeksiyon tanı kriterlerine göre, akut piyelonefrit (n=39) ve sistit (n=43) grupları olarak ayrıldı. Ateş, C-reaktif protein, beyaz küre hücresi, eritrosit sedimentasyon hızı ve interlökin-8 düzeyleri değerlendirildi. Bulgular: İki çalışma grubu arasında ateş, CRP ve ESH düzeyleri açısından anlamlı farklılık saptandı (p<0,05). Ayrıca piyelonefrit grubunda idrar interlökin-8 düzeyi (medyan 499 pg/ml) sistit grubuna (252,1 pg/ml) göre anlamlı yüksek saptandı (p<0,001). Ayrıca idrar interlökin-8 düzeyi idrar lökosit sayısıyla korele saptandı (r=0,5, p<0,005). Sonuç: Bu bulgular, ateşli çocuklarda akut piyelonefritin erken tanısında idrar IL-8 düzeyinin yararlı bir tanısal belirteç olduğunu göstermektedir.Anahtar kelimeler: Akut piyelonefrit, çocuklar, interlökin-8, idrar yolu enfeksiyonu ABSTRACT Objective: Urinary tract infection is a common infectious disease in children and it takes the first place among diseases which cause chronic kidney disease in our country. The inflammatory cytokine interleukin-8 plays an important role in response to bacterial infection. The aim of this study is to evaluate the effects of urine interleukin-8 level on diagnosis and localization of urinary tract infection. Methods: A total of 82 children aged 1 month to 15 years with urinary tract infection and 49 healthy children were included in the study. The patients were divided into the acute pyelonephritis group (n=39) and cystitis group (n=43) according to the Jodal's criteria of urinary tract infection (UTI). Body temperature, C-reactive protein; white blood cell count; erythrocyte sedimentation rate and interleukin-8 levels were evaluated. Results: There was a significant difference between two study groups related with fever, C-reactive protein and erythrocyte sedimentation rate (p<0.05). Significantly, higher urine interleukin-8 levels were found in children with acute pyelonephritis (median 499 pg/ml) than in those with cystitis (252.1 pg/ml) (p<0.001). Also, urine interleukin-8 in children were positively correlated with urine leukocyte counts (r=0.5, p<0.005). Conclusion: These results indicate that urine interleukin-8 level is a useful diagnostic marker for early recognition of acute pyelonephritis in febrile children.

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Urine interleukin-6 and interleukin-8 in children with acute pyelonephritis, in relation to DMSA scintigraphy in the acute phase and at 1-year follow-up

Cited by 53 publications

References 22 publications

Cytokine Profiles of Pediatric Patients Treated with Antibiotics for Pyelonephritis: Potential Therapeutic Impact

Cytokine Profiles of Pediatric Patients Treated with Antibiotics for Pyelonephritis: Potential Therapeutic Impact

Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinases-1 in Acute Pyelonephritis and Renal Scarring

Urine levels of interleukin-8 as diagnostic marker of acute pyelonephritis in children

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