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      Cytokines and Cell Adhesion Molecules in the Inflammatory Response during Acute Pyelonephritis

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          Abstract

          Urinary tract infection is a common bacterial infection of childhood. Renal parenchymal scarring, a recognised complication of urinary tract infection, is responsible for up to 24% of children entering end-stage renal failure. Why acute inflammation results in renal scarring in some children whilst in others complete resolution occurs without scarring is at present poorly understood. This article reviews the role of the cytokines, adhesion molecules and growth factors in the inflammatory response during acute pyelonephritis and renal parenchymal scarring. We hypothesize that inter-individual variability in cellular response may in part be responsible for this variable clinical outcome.

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          Most cited references 11

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          Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock.

          Septic shock remains a significant health concern worldwide, and despite progress in understanding the physiological and molecular basis of septic shock, the high mortality rate of patients with septic shock remains unchanged. We recently identified a common polymorphism in toll-like receptor 4 (TLR4) that is associated with hyporesponsiveness to inhaled endotoxin or lipopolysaccharide in humans. Since TLR4 is a major receptor for lipopolysaccharide in mammals and gram-negative bacteria are the prevalent pathogen associated with septic shock, we investigated whether these specific TLR4 alleles are associated with a predisposition to a more severe disease outcome for patients with septic shock. We genotyped 91 patients with septic shock as well as 73 healthy blood donor controls for the presence of the TLR4 Asp299Gly and TLR4 Thr399Ile mutations. We found the TLR4 Asp299Gly allele exclusively in patients with septic shock (P =.05). Furthermore, patients with septic shock with the TLR4 Asp299Gly/Thr399Ile alleles had a higher prevalence of gram-negative infections. Mutations in the TLR4 receptor may predispose people to develop septic shock with gram-negative microorganisms.
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            Imaging studies after a first febrile urinary tract infection in young children.

            Guidelines from the American Academy of Pediatrics recommend obtaining a voiding cystourethrogram and a renal ultrasonogram for young children after a first urinary tract infection; renal scanning with technetium-99m-labeled dimercaptosuccinic acid has also been endorsed by other authorities. We investigated whether imaging studies altered management or improved outcomes in young children with a first febrile urinary tract infection. In a prospective trial involving 309 children (1 to 24 months old), an ultrasonogram and an initial renal scan were obtained within 72 hours after diagnosis, contrast voiding cystourethrography was performed one month later, and renal scanning was repeated six months later. The ultrasonographic results were normal in 88 percent of the children (272 of 309); the identified abnormalities did not modify management. Acute pyelonephritis was diagnosed in 61 percent of the children (190 of 309). Thirty-nine percent of the children who underwent cystourethrography (117 of 302) had vesicoureteral reflux; 96 percent of these children (112 of 117) had grade I, II, or III vesicoureteral reflux. Repeated scans were obtained for 89 percent of the children (275 of 309); renal scarring was noted in 9.5 percent of these children (26 of 275). An ultrasonogram performed at the time of acute illness is of limited value. A voiding cystourethrogram for the identification of reflux is useful only if antimicrobial prophylaxis is effective in reducing reinfections and renal scarring. Renal scans obtained at presentation identify children with acute pyelonephritis, and scans obtained six months later identify those with renal scarring. The routine performance of urinalysis, urine culture, or both during subsequent febrile illnesses in all children with a previous febrile urinary tract infection will probably obviate the need to obtain either early or late scans. Copyright 2003 Massachusetts Medical Society
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              Interleukin 8 Receptor Deficiency Confers Susceptibility to Acute Experimental Pyelonephritis and May Have a Human Counterpart

              Neutrophils migrate to infected mucosal sites that they protect against invading pathogens. Their interaction with the epithelial barrier is controlled by CXC chemokines and by their receptors. This study examined the change in susceptibility to urinary tract infection (UTI) after deletion of the murine interleukin 8 receptor homologue (mIL-8Rh). Experimental UTIs in control mice stimulated an epithelial chemokine response and increased chemokine receptor expression. Neutrophils migrated through the tissues to the epithelial barrier that they crossed into the lumen, and the mice developed pyuria. In mIL-8Rh knockout (KO) mice, the chemokine response was intact, but the epithelial cells failed to express IL-8R, and neutrophils accumulated in the tissues. The KO mice were unable to clear bacteria from kidneys and bladders and developed bacteremia and symptoms of systemic disease, but control mice were fully resistant to infection. The experimental UTI model demonstrated that IL-8R–dependent mechanisms control the urinary tract defense, and that neutrophils are essential host effector cells. Patients prone to acute pyelonephritis also showed low CXC chemokine receptor 1 expression compared with age-matched controls, suggesting that chemokine receptor expression may also influence the susceptibility to UTIs in humans. The results provide a first molecular clue to disease susceptibility of patients prone to acute pyelonephritis.
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                Author and article information

                Journal
                NEE
                Nephron Exp Nephrol
                10.1159/issn.1660-2129
                Cardiorenal Medicine
                S. Karger AG
                1660-2129
                2004
                January 2004
                17 November 2004
                : 96
                : 1
                : e1-e6
                Affiliations
                aDepartment of Paediatric Nephrology, Royal Manchester Children’s Hospital and bRenal Research Laboratories, Manchester Institute for Nephrology and Transplantation, Manchester Royal Infirmary, Manchester, UK
                Article
                75570 Nephron Exp Nephrol 2004;96:e1–e6
                10.1159/000075570
                14752242
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, References: 30, Pages: 1
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                Self URI (application/pdf): https://www.karger.com/Article/Pdf/75570
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