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The pathogenesis and management of renal scarring in children with vesicoureteric reflux and pyelonephritis

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Abstract

Bacterial urinary tract infections (UTIs) are one of the most common reasons for children to be admitted to hospital. Bacteria infect and invade the bladder (the lower urinary tract) and if the infection disseminates to the upper urinary tract, significant inflammation in the kidneys may arise. Inflammation is a double-edged sword: it is needed to clear bacteria, but if excessive, kidney tissue is injured. During injury, nephrons are destroyed and replaced with deposition of extracellular matrix and a renal scar. In this review, we explore the pathogenesis of UTIs and discuss the risk factors that result in dissemination of bladder infection to the kidneys. Three major risk factors predispose to kidney infections: the presence of vesicoureteric reflux, the presence of bladder and bowel dysfunction, and defects in the ability of the host immune response to clear bacteria. In this review, we will discuss these factors, their relationship to renal scarring, and potential treatments that might be beneficial to prevent renal scar formation in children.

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References

  1. CORR (2010) Annual report. http://secure.cihi.ca/cihiweb/products/2011_CORR_Annual_Report_final_e.pdf. Accessed 23 Nov. 2018

  2. NAPRTCS (2014) Annual transplant report. https://web.emmes.com/study/ped/annlrept/annualrept2014.pdf. Accessed 23 Nov. 2018

  3. Ardissino G, Dacco V, Testa S, Bonaudo R, Claris-Appiani A, Taioli E, Marra G, Edefonti A, Sereni F (2003) Epidemiology of chronic renal failure in children: data from the ItalKid project. Pediatrics 111:e382–e387

    Article  PubMed  Google Scholar 

  4. Keren R, Shaikh N, Pohl H, Gravens-Mueller L, Ivanova A, Zaoutis L, Patel M, de Berardinis R, Parker A, Bhatnagar S, Haralam MA, Pope M, Kearney D, Sprague B, Barrera R, Viteri B, Egigueron M, Shah N, Hoberman A (2015) Risk factors for recurrent urinary tract infection and renal scarring. Pediatrics 136:e13–e21. https://doi.org/10.1542/peds.2015-0409

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hoberman A, RIVUR Trial Investigators, Greenfield SP, Mattoo TK et al (2014) Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med 370:2367–2376. https://doi.org/10.1056/NEJMoa1401811

    Article  CAS  PubMed  Google Scholar 

  6. Mattoo TK, Chesney RW, Greenfield SP, Hoberman A, Keren R, Mathews R, Gravens-Mueller L, Ivanova A, Carpenter MA, Moxey-Mims M, Majd M, Ziessman HA, RIVUR Trial Investigators (2016) Renal scarring in the randomized intervention for children with vesicoureteral reflux (RIVUR) Trial. Clin J Am Soc Nephrol 11:54–61. https://doi.org/10.2215/CJN.05210515

    Article  CAS  PubMed  Google Scholar 

  7. Nguyen HT, Bauer SB, Peters CA, Connolly LP, Gobet R, Borer JG, Barnewolt CE, Ephraim PL, Treves ST, Retik AB (2000) 99m Technetium dimercapto-succinic acid renal scintigraphy abnormalities in infants with sterile high grade vesicoureteral reflux. J Urol 164:1674–1678 discussion 1678-1679

    Article  CAS  PubMed  Google Scholar 

  8. Silva JM, Oliveira EA, Diniz JS, Cardoso LS, Vergara RM, Vasconcelos MA, Santo DE (2006) Gender and vesico-ureteral reflux: a multivariate analysis. Pediatr Nephrol 21:510–516. https://doi.org/10.1007/s00467-006-0011-z

    Article  PubMed  Google Scholar 

  9. Gilliver SC, Ashworth JJ, Mills SJ, Hardman MJ, Ashcroft GS (2006) Androgens modulate the inflammatory response during acute wound healing. J Cell Sci 119:722–732. https://doi.org/10.1242/jcs.02786

    Article  CAS  PubMed  Google Scholar 

  10. Olson PD, Hruska KA, Hunstad DA (2016) Androgens enhance male urinary tract infection severity in a new model. J Am Soc Nephrol 27:1625–1634. https://doi.org/10.1681/asn.2015030327

    Article  CAS  PubMed  Google Scholar 

  11. Lee G, Romih R, Zupančič D (2014) Cystitis: from urothelial cell biology to clinical applications. Biomed Res Int 2014:10. https://doi.org/10.1155/2014/473536

    Article  Google Scholar 

  12. Deo SS, Vaidya AK (2004) Elevated levels of secretory immunoglobulin A (sIgA) in urinary tract infections. Indian J Pediatr 71:37–40

    Article  PubMed  Google Scholar 

  13. Valore EV, Park CH, Quayle AJ, Wiles KR, McCray PBJ, Ganz T (1998) Human beta-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 101:1633–1642. https://doi.org/10.1172/JCI1861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chromek M, Slamová Z, Bergman P, Kovács L, Lu P, Ehrén I, Hökfelt T, Gudmundsson GH, Gallo RL, Agerberth B, Brauner A (2006) The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat Med 12:636. https://doi.org/10.1038/nm1407https://www.nature.com/articles/nm1407#supplementary-information

    Article  CAS  PubMed  Google Scholar 

  15. Nielsen KL, Dynesen P, Larsen P, Jakobsen L, Andersen PS, Frimodt-Møller N (2014) Role of urinary cathelicidin LL-37 and human β-defensin 1 in uncomplicated Escherichia coli urinary tract infections. Infect Immun 82:1572–1578. https://doi.org/10.1128/iai.01393-13

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sivick KE, Schaller MA, Smith SN, Mobley HLT (2010) The innate immune response to Uropathogenic Escherichia coli involves IL-17A in a murine model of urinary tract infection. J Immunol 184:2065. https://doi.org/10.4049/jimmunol.0902386

    Article  CAS  PubMed  Google Scholar 

  17. Samuelsson P, Hang L, Wullt B, Irjala H, Svanborg C (2004) Toll-like receptor 4 expression and cytokine responses in the human urinary tract mucosa. Infect Immun 72:3179–3186. https://doi.org/10.1128/IAI.72.6.3179-3186.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Song J, Abraham SN (2008) TLR mediated immune responses in the urinary tract. Curr Opin Microbiol 11:66–73. https://doi.org/10.1016/j.mib.2007.12.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhang D, Zhang G, Hayden MS, Greenblatt MB, Bussey C, Flavell RA, Ghosh S (2004) A toll-like receptor that prevents infection by uropathogenic bacteria. Science 303:1522–1526. https://doi.org/10.1126/science.1094351

    Article  CAS  PubMed  Google Scholar 

  20. Godaly G, Bergsten G, Hang L, Fischer H, Frendéus B, Lundstedt A-C, Samuelsson M, Samuelsson P, Svanborg C (2001) Neutrophil recruitment, chemokine receptors, and resistance to mucosal infection. J Leukoc Biol 69:899–906. https://doi.org/10.1189/jlb.69.6.899

    Article  CAS  PubMed  Google Scholar 

  21. Song J, Bishop BL, Li G, Duncan MJ, Abraham SN (2007) TLR4-initiated and cAMP-mediated abrogation of bacterial invasion of the bladder. Cell Host Microbe 1:287–298. https://doi.org/10.1016/j.chom.2007.05.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Song J, Duncan MJ, Li G, Chan C, Grady R, Stapleton A, Abraham SN (2007) A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells. PLoS Pathog 3:e60. https://doi.org/10.1371/journal.ppat.0030060

  23. Spencer JD, Schwaderer AL, Becknell B, Watson J, Hains DS (2014) The innate immune response during urinary tract infection and pyelonephritis. Pediatr Nephrol 29:1139–1149. https://doi.org/10.1007/s00467-013-2513-9

    Article  PubMed  Google Scholar 

  24. Ingersoll MA, Kline KA, Nielsen HV, Hultgren SJ (2008) G-CSF induction early in uropathogenic Escherichia coli infection of the urinary tract modulates host immunity. Cell Microbiol 10:2568–2578. https://doi.org/10.1111/j.1462-5822.2008.01230.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lacerda Mariano L, Ingersoll MA (2018) Bladder resident macrophages: mucosal sentinels. Cell Immunol. https://doi.org/10.1016/j.cellimm.2018.01.018

  26. Song J, Bishop BL, Li G, Grady R, Stapleton A, Abraham SN (2009) TLR4-mediated expulsion of bacteria from infected bladder epithelial cells. Proc Natl Acad Sci U S A 106:14966–14971. https://doi.org/10.1073/pnas.0900527106

    Article  PubMed  PubMed Central  Google Scholar 

  27. Isaacson B, Hadad T, Glasner A, Gur C, Granot Z, Bachrach G, Mandelboim O (2017) Stromal cell-derived factor 1 mediates immune cell attraction upon urinary tract infection. Cell Rep 20:40–47. https://doi.org/10.1016/j.celrep.2017.06.034

    Article  CAS  PubMed  Google Scholar 

  28. Nienhouse V, Gao X, Dong Q, Nelson DE, Toh E, McKinley K, Schreckenberger P, Shibata N, Fok CS, Mueller ER, Brubaker L, Wolfe AJ, Radek KA (2014) Interplay between bladder microbiota and urinary antimicrobial peptides: mechanisms for human urinary tract infection risk and symptom severity. PLoS One 9:e114185. https://doi.org/10.1371/journal.pone.0114185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Liu XJ, Tan Y, Geng YQ, Wang Z, Ye JH, Yin XY, Fu B (2014) Proximal tubule toll-like receptor 4 expression linked to inflammation and apoptosis following hypoxia/reoxygenation injury. Am J Nephrol 39:337–347. https://doi.org/10.1159/000360549

    Article  CAS  PubMed  Google Scholar 

  30. Chassin C, Goujon JM, Darche S, du Merle L, Bens M, Cluzeaud F, Werts C, Ogier-Denis E, Le Bouguenec C, Buzoni-Gatel D, Vandewalle A (2006) Renal collecting duct epithelial cells react to pyelonephritis-associated Escherichia coli by activating distinct TLR4-dependent and -independent inflammatory pathways. J Immunol 177:4773–4784. https://doi.org/10.4049/jimmunol.177.7.4773

    Article  CAS  PubMed  Google Scholar 

  31. Tittel AP, Heuser C, Ohliger C, Knolle PA, Engel DR, Kurts C (2011) Kidney dendritic cells induce innate immunity against bacterial pyelonephritis. J Am Soc Nephrol 22:1435–1441. https://doi.org/10.1681/ASN.2010101072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bens M, Vimont S, Ben Mkaddem S, Chassin C, Goujon JM, Balloy V, Chignard M, Werts C, Vandewalle A (2014) Flagellin/TLR5 signalling activates renal collecting duct cells and facilitates invasion and cellular translocation of uropathogenic Escherichia coli. Cell Microbiol 16:1503–1517. https://doi.org/10.1111/cmi.12306

    Article  CAS  PubMed  Google Scholar 

  33. Weisheit CK, Engel DR, Kurts C (2015) Dendritic cells and macrophages: sentinels in the kidney. Clin J Am Soc Nephrol 10:1841–1851. https://doi.org/10.2215/CJN.07100714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bates JM, Raffi HM, Prasadan K, Mascarenhas R, Laszik Z, Maeda N, Hultgren SJ, Kumar S (2004) Tamm-Horsfall protein knockout mice are more prone to urinary tract infection: rapid communication. Kidney Int 65:791–797. https://doi.org/10.1111/j.1523-1755.2004.00452.x

    Article  CAS  PubMed  Google Scholar 

  35. Saemann MD, Weichhart T, Horl WH, Zlabinger GJ (2005) Tamm-Horsfall protein: a multilayered defence molecule against urinary tract infection. Eur J Clin Investig 35:227–235. https://doi.org/10.1111/j.1365-2362.2005.01483.x

    Article  CAS  Google Scholar 

  36. Svensson M, Yadav M, Holmqvist B, Lutay N, Svanborg C, Godaly G (2011) Acute pyelonephritis and renal scarring are caused by dysfunctional innate immunity in mCxcr2 heterozygous mice. Kidney Int 80:1064–1072. https://doi.org/10.1038/ki.2011.257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Dustin ML, Rothlein R, Bhan AK, Dinarello CA, Springer TA (1986) Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol 137:245–254

    CAS  PubMed  Google Scholar 

  38. Woodfin A, Beyrau M, Voisin M-B, Ma B, Whiteford JR, Hordijk PL, Hogg N, Nourshargh S (2016) ICAM-1–expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia. Blood 127:898–907. https://doi.org/10.1182/blood-2015-08-664995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hughes BJ, Hollers JC, Crockett-Torabi E, Smith CW (1992) Recruitment of CD11b/CD18 to the neutrophil surface and adherence-dependent cell locomotion. J Clin Invest 90:1687–1696. https://doi.org/10.1172/jci116041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bowen SE, Watt CL, Murawski IJ, Gupta IR, Abraham SN (2013) Interplay between vesicoureteric reflux and kidney infection in the development of reflux nephropathy in mice. Dis Model Mech 6:934–941. https://doi.org/10.1242/dmm.011650

    Article  PubMed  PubMed Central  Google Scholar 

  41. Hang L, Frendéus B, Godaly G, Svanborg C (2000) Interleukin-8 receptor knockout mice have subepithelial neutrophil entrapment and renal scarring following acute pyelonephritis. J Infect Dis 182:1738–1748. https://doi.org/10.1086/317599

    Article  CAS  PubMed  Google Scholar 

  42. De Groote MA, Ochsner UA, Shiloh MU, Nathan C, McCord JM, Dinauer MC, Libby SJ, Vazquez-Torres A, Xu Y, Fang FC (1997) Periplasmic superoxide dismutase protects Salmonella from products of phagocyte NADPH-oxidase and nitric oxide synthase. Proc Natl Acad Sci U S A 94:13997–14001

    Article  PubMed  PubMed Central  Google Scholar 

  43. Tan TK, Zheng G, Hsu TT, Lee SR, Zhang J, Zhao Y, Tian X, Wang Y, Wang YM, Cao Q, Wang Y, Lee VW, Wang C, Zheng D, Alexander SI, Thompson E, Harris DC (2013) Matrix metalloproteinase-9 of tubular and macrophage origin contributes to the pathogenesis of renal fibrosis via macrophage recruitment through osteopontin cleavage. Lab Investig 93:434–449. https://doi.org/10.1038/labinvest.2013.3

    Article  CAS  PubMed  Google Scholar 

  44. Lee S, Huen S, Nishio H, Nishio S, Lee HK, Choi B-S, Ruhrberg C, Cantley LG (2011) Distinct macrophage phenotypes contribute to kidney injury and repair. J Am Soc Nephrol 22:317–326. https://doi.org/10.1681/asn.2009060615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jin Y, Liu R, Xie J, Xiong H, He JC, Chen N (2013) Interleukin-10 deficiency aggravates kidney inflammation and fibrosis in the unilateral ureteral obstruction mouse model. Lab Investig 93:801. https://doi.org/10.1038/labinvest.2013.64

    Article  CAS  PubMed  Google Scholar 

  46. Rodell CB, Rai R, Faubel S, Burdick JA, Soranno DE (2015) Local immunotherapy via delivery of interleukin-10 and transforming growth factor β antagonist for treatment of chronic kidney disease. J Control Release 206:131–139. https://doi.org/10.1016/j.jconrel.2015.03.025

    Article  CAS  PubMed  Google Scholar 

  47. Nielubowicz GR, Mobley HLT (2010) Host–pathogen interactions in urinary tract infection. Nat Rev Urol 7:430. https://doi.org/10.1038/nrurol.2010.101

    Article  CAS  PubMed  Google Scholar 

  48. Paragas N, Kulkarni R, Werth M, Schmidt-Ott KM, Forster C, Deng R, Zhang Q, Singer E, Klose AD, Shen TH, Francis KP, Ray S, Vijayakumar S, Seward S, Bovino ME, Xu K, Takabe Y, Amaral FE, Mohan S, Wax R, Corbin K, Sanna-Cherchi S, Mori K, Johnson L, Nickolas T, D'Agati V, Lin C-S, Qiu A, Al-Awqati Q, Ratner AJ, Barasch J (2014) α-Intercalated cells defend the urinary system from bacterial infection. J Clin Invest 124:2963–2976. https://doi.org/10.1172/JCI71630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK (2002) The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 10:1033–1043

    Article  CAS  PubMed  Google Scholar 

  50. Owusu-Boaitey N, Bauckman KA, Zhang T, Mysorekar IU (2016) Macrophagic control of the response to uropathogenic E. coli infection by regulation of iron retention in an IL-6-dependent manner. Immun Inflamm Dis 4:413–426. https://doi.org/10.1002/iid3.123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Thumbikat P, Waltenbaugh C, Schaeffer AJ, Klumpp DJ (2006) Antigen-specific responses accelerate bacterial clearance in the bladder. J Immunol 176:3080–3086

    Article  CAS  PubMed  Google Scholar 

  52. Mora-Bau G, Platt AM, van Rooijen N, Randolph GJ, Albert ML, Ingersoll MA (2015) Macrophages subvert adaptive immunity to urinary tract infection. PLoS Pathog 11:e1005044. https://doi.org/10.1371/journal.ppat.1005044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Chan CY, St John AL, Abraham SN (2013) Mast cell interleukin-10 drives localized tolerance in chronic bladder infection. Immunity 38:349–359. https://doi.org/10.1016/j.immuni.2012.10.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Huttner A, Hatz C, van den Dobbelsteen G, Abbanat D, Hornacek A, Frolich R, Dreyer AM, Martin P, Davies T, Fae K, van den Nieuwenhof I, Thoelen S, de Valliere S, Kuhn A, Bernasconi E, Viereck V, Kavvadias T, Kling K, Ryu G, Hulder T, Groger S, Scheiner D, Alaimo C, Harbarth S, Poolman J, Fonck VG (2017) Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic Escherichia coli in women with a history of recurrent urinary tract infection: a randomised, single-blind, placebo-controlled phase 1b trial. Lancet Infect Dis 17:528–537. https://doi.org/10.1016/S1473-3099(17)30108-1

    Article  CAS  PubMed  Google Scholar 

  55. Nagler EV, Williams G, Hodson EM, Craig JC (2011) Interventions for primary vesicoureteric reflux. Cochrane Database Syst Rev 6:CD001532. https://doi.org/10.1002/14651858.CD001532.pub4

    Article  Google Scholar 

  56. Bahat Özdoğan E, Özdemir T, Arslansoyu Çamlar S, İmamoğlu M, Çobanoğlu Ü, Sönmez B, Tosun İ, Doğan İ (2014) Could pyelonephritic scarring be prevented by anti-inflammatory treatment? An experimental model of acute pyelonephritis. Biomed Res Int 2014:134940. https://doi.org/10.1155/2014/134940

    Article  PubMed  PubMed Central  Google Scholar 

  57. Huang Y-Y, Chen M-J, Chiu N-T, Chou H-H, Lin K-Y, Chiou Y-Y (2011) Adjunctive oral methylprednisolone in pediatric acute pyelonephritis alleviates renal scarring. Pediatrics 128:e496–e504. https://doi.org/10.1542/peds.2010-0297

    Article  PubMed  Google Scholar 

  58. Brown KH, Gaffar A, Alamgir SM (1979) Xerophthalmia, protein-calorie malnutrition, and infections in children. J Pediatr 95:651–656

    Article  CAS  PubMed  Google Scholar 

  59. Kavukcu S, Soylu A, Turkmen M, Sarioglu S, Buyukgebiz B, Gure A (1999) The role of vitamin a in preventing renal scarring secondary to pyelonephritis. BJU Int 83:1055–1059

    Article  CAS  PubMed  Google Scholar 

  60. Zhang G-Q, Chen J-L, Zhao Y (2016) The effect of vitamin a on renal damage following acute pyelonephritis in children: a meta-analysis of randomized controlled trials. Pediatr Nephrol 31:373–379. https://doi.org/10.1007/s00467-015-3098-2

    Article  PubMed  Google Scholar 

  61. Huang A, Palmer LS, Hom D, Anderson AE, Kushner L, Franco I (1999) Ibuprofen combined with antibiotics suppresses renal scarring due to ascending pyelonephritis in rats. J Urol 162:1396–1398

    Article  CAS  PubMed  Google Scholar 

  62. Matsumoto T, Mizunoe Y, Sakamoto N, Kumazawa J (1990) Suitability of colchicine and superoxide dismutase for the suppression of renal scarring following an infection with bacteria showing mannose-sensitive pili. Nephron 56:130–135. https://doi.org/10.1159/000186120

    Article  CAS  PubMed  Google Scholar 

  63. Delanian S, Baillet F, Huart J, Lefaix JL, Maulard C, Housset M (1994) Successful treatment of radiation-induced fibrosis using liposomal Cu/Zn superoxide dismutase: clinical trial. Radiother Oncol 32:12–20

    Article  CAS  PubMed  Google Scholar 

  64. Zhang H, Sun C, Glogauer M, Bokoch GM (2009) Human neutrophils coordinate chemotaxis by differential activation of Rac1 and Rac2. J Immunol. https://doi.org/10.4049/jimmunol.0900849

  65. Joshi S, Singh AR, Wong SS, Zulcic M, Jiang M, Pardo A, Selman M, Hagood JS, Durden DL (2017) Rac2 is required for alternative macrophage activation and bleomycin induced pulmonary fibrosis; a macrophage autonomous phenotype. PLoS One 12:e0182851. https://doi.org/10.1371/journal.pone.0182851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Amar S, Fields GB (2015) Potential clinical implications of recent MMP inhibitor design strategies. Expert Rev Proteomics 12:445–447. https://doi.org/10.1586/14789450.2015.1069190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gossage DL, Cieslarova B, Ap S, Zheng H, Xin Y, Lal P, Chen G, Smith V, Sundy JS (2018) Phase 1b study of the safety, pharmacokinetics, and disease-related outcomes of the matrix Metalloproteinase-9 inhibitor Andecaliximab in patients with rheumatoid arthritis. Clin Ther 40:156–165.e155. https://doi.org/10.1016/j.clinthera.2017.11.011

    Article  CAS  PubMed  Google Scholar 

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  1. McGill University Health Centre, Montreal, Canada

    Vasikar Murugapoopathy & Christine McCusker

  2. Montreal Childrens Hospital, Montreal, Quebec, Canada

    Indra R. Gupta

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Murugapoopathy, V., McCusker, C. & Gupta, I.R. The pathogenesis and management of renal scarring in children with vesicoureteric reflux and pyelonephritis. Pediatr Nephrol 35, 349–357 (2020). https://doi.org/10.1007/s00467-018-4187-9

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