{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:58:09Z","timestamp":1791313089760,"version":"4.3.1"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"JSPS KAKENHI","award":["20K818100"],"award-info":[{"award-number":["20K818100"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Nephrol"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract\n<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The current study tested the hypothesis that urinary angiotensinogen (UAGT) and urinary monocyte chemoattractant protein-1 (UMCP-1) levels provide a specific index of intrarenal renin\u2013angiotensin system (RAS) status and the degree of infiltration of macrophages associated with RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We measured baseline UAGT and UMCP-1 levels to examine the correlation between glomerular injury in 48 pediatric chronic glomerulonephritis patients before treatment. Furthermore, we performed immunohistochemical analysis of angiotensinogen (AGT) and CD68 in 27 pediatric chronic glomerulonephritis patients treated with RAS blockades and immunosuppressants for 2\u00a0years. Finally, we examined the effects of angiotensin II (Ang II) on monocyte chemoattractant protein-1 (MCP-1) expression in cultured human mesangial cells (MCs).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Baseline UAGT and UMCP-1 levels positively correlated with urinary protein levels, scores for mesangial hypercellularity, rate of crescentic formation, and expression levels of AGT and CD68 in renal tissues (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). UAGT and UMCP-1 levels were significantly decreased after RAS blockade and immunosuppressant treatment (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), which was accompanied by AGT and CD68 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), as well as the magnitude of glomerular injury. Cultured human MCs showed increased MCP-1 messenger ribonucleic acid and protein levels after Ang II treatment (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The data indicates that UAGT and UMCP-1 are useful biomarkers of the degree of glomerular injury during RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00467-023-06026-5","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T17:01:47Z","timestamp":1685034107000},"page":"3711-3719","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Intrarenal renin\u2013angiotensin system activation and macrophage infiltrations in pediatric chronic glomerulonephritis"],"prefix":"10.1007","volume":"38","author":[{"given":"Tomoki","family":"Hattori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Fujioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoji","family":"Kagami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Hirayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6431-3239","authenticated-orcid":false,"given":"Maki","family":"Urushihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"6026_CR1","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1124\/pr.59.3.3","volume":"59","author":"H Kobori","year":"2007","unstructured":"Kobori H, Nangaku M, Navar LG, Nishiyama A (2007) The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev 59:251\u2013287","journal-title":"Pharmacol Rev"},{"key":"6026_CR2","doi-asserted-by":"publisher","first-page":"601786","DOI":"10.1155\/2012\/601786","volume":"2012","author":"M Urushihara","year":"2012","unstructured":"Urushihara M, Kinoshita Y, Kondo S, Kagami S (2012) Involvement of the intrarenal renin-angiotensin system in experimental models of glomerulonephritis. J Biomed Biotechnol 2012:601786","journal-title":"J Biomed Biotechnol"},{"key":"6026_CR3","first-page":"3","volume":"465","author":"H Kobori","year":"2013","unstructured":"Kobori H, Urushihara M (2013) Augmented intrarenal and urinary angiotensinogen in hypertension and chronic kidney disease. Pflugers Arch 465:3\u201312","journal-title":"Pflugers Arch"},{"key":"6026_CR4","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1007\/s00467-008-0801-6","volume":"23","author":"M Takamatsu","year":"2008","unstructured":"Takamatsu M, Urushihara M, Kondo S, Shimizu M, Morioka T, Oite T, Kobori H, Kagami S (2008) Glomerular angiotensinogen protein is enhanced in pediatric IgA nephropathy. Pediatr Nephrol 23:1257\u20131267","journal-title":"Pediatr Nephrol"},{"key":"6026_CR5","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1007\/s00467-014-3028-8","volume":"30","author":"M Urushihara","year":"2015","unstructured":"Urushihara M, Nagai T, Kinoshita Y, Nishiyama S, Suga K, Ozaki N, Jamba A, Kondo S, Kobori H, Kagami S (2015) Changes in urinary angiotensinogen posttreatment in pediatric IgA nephropathy patients. Pediatr Nephrol 30:975\u2013982","journal-title":"Pediatr Nephrol"},{"key":"6026_CR6","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1016\/S0140-6736(76)90480-3","volume":"1","author":"RC Atkins","year":"1976","unstructured":"Atkins RC, Holdsworth SR, Glasgow EF, Matthews FE (1976) The macrophagen in human rapidly progressive glomerulonephritis. Lancet 1:830\u2013832","journal-title":"Lancet"},{"key":"6026_CR7","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1084\/jem.147.2.369","volume":"147","author":"GF Schreiner","year":"1978","unstructured":"Schreiner GF, Cotran RS, Pardo V, Unanue ER (1978) A mononuclear cell component in experimental immunological glomerulonephritis. J Exp Med 147:369\u2013384","journal-title":"J Exp Med"},{"key":"6026_CR8","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s40620-015-0252-7","volume":"30","author":"CB Dias","year":"2017","unstructured":"Dias CB, Malafronte P, Lee J, Resende A, Jorge L, Pinheiro CC, Malheiros D, Woronik V (2017) Role of renal expression of CD68 in the long-term prognosis of proliferative lupus nephritis. J Nephrol 30:87\u201394","journal-title":"J Nephrol"},{"key":"6026_CR9","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.1093\/ndt\/gfh487","volume":"19","author":"FW Tam","year":"2004","unstructured":"Tam FW, Sanders JS, George A, Hammad T, Miller C, Dougan T, Cook HT, Kallenberg CG, Gaskin G, Levy JB, Pusey CD (2004) Urinary monocyte chemoattractant protein-1 (MCP-1) is a marker of active renal vasculitis. Nephrol Dial Transplant 19:2761\u20132768","journal-title":"Nephrol Dial Transplant"},{"key":"6026_CR10","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1681\/ASN.V11122231","volume":"11","author":"S Segerer","year":"2000","unstructured":"Segerer S, Cui Y, Hudkins KL, Goodpaster T, Eitner F, Mack M, Schlondorff D, Alpers CE (2000) Expression of the chemokine monocyte chemoattractant protein-1 and its receptor chemokine receptor 2 in human crescentic glomerulonephritis. J Am Soc Nephrol 11:2231\u20132242","journal-title":"J Am Soc Nephrol"},{"key":"6026_CR11","doi-asserted-by":"publisher","first-page":"F330","DOI":"10.1152\/ajprenal.00059.2006","volume":"292","author":"Y Ozawa","year":"2007","unstructured":"Ozawa Y, Kobori H, Suzaki Y, Navar LG (2007) Sustained renal interstitial macrophage infiltration following chronic angiotensin II infusions. Am J Physiol Renal Physiol 292:F330-339","journal-title":"Am J Physiol Renal Physiol"},{"key":"6026_CR12","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1161\/HYPERTENSIONAHA.110.165704","volume":"57","author":"M Urushihara","year":"2011","unstructured":"Urushihara M, Ohashi N, Miyata K, Satou R, Acres OW, Kobori H (2011) Addition of angiotensin II type 1 receptor blocker to CCR2 antagonist markedly attenuates crescentic glomerulonephritis. Hypertension 57:586\u2013593","journal-title":"Hypertension"},{"key":"6026_CR13","doi-asserted-by":"publisher","first-page":"247","DOI":"10.7326\/0003-4819-145-4-200608150-00004","volume":"145","author":"AS Levey","year":"2006","unstructured":"Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F (2006) Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145:247\u2013254","journal-title":"Ann Intern Med"},{"key":"6026_CR14","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1373\/clinchem.2006.077180","volume":"53","author":"AS Levey","year":"2007","unstructured":"Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW, Van Lente F (2007) Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 53:766\u2013772","journal-title":"Clin Chem"},{"key":"6026_CR15","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1159\/000286037","volume":"31","author":"M Urushihara","year":"2010","unstructured":"Urushihara M, Kondo S, Kagami S, Kobori H (2010) Urinary angiotensinogen accurately reflects intrarenal Renin-Angiotensin system activity. Am J Nephrol 31:318\u2013325","journal-title":"Am J Nephrol"},{"key":"6026_CR16","doi-asserted-by":"crossref","unstructured":"Working Group of the International Ig ANN, the Renal Pathology S, Cattran DC, Coppo R, Cook HT, Feehally J, Roberts IS, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, D'Agati V, D'Amico G, Emancipator S, Emma F, Ferrario F, Fervenza FC, Florquin S, Fogo A, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hogg RJ, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Leung CB, Li LS, Li PK, Liu ZH, Mackinnon B, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H (2009) The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int 76:534-545","DOI":"10.1038\/ki.2009.243"},{"key":"6026_CR17","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1007\/s00467-011-2061-0","volume":"27","author":"Y Shima","year":"2012","unstructured":"Shima Y, Nakanishi K, Hama T, Mukaiyama H, Togawa H, Hashimura Y, Kaito H, Sako M, Iijima K, Yoshikawa N (2012) Validity of the Oxford classification of IgA nephropathy in children. Pediatr Nephrol 27:783\u2013792","journal-title":"Pediatr Nephrol"},{"key":"6026_CR18","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1136\/bmj.2.6078.11","volume":"2","author":"R Counahan","year":"1977","unstructured":"Counahan R, Winterborn MH, White RH, Heaton JM, Meadow SR, Bluett NH, Swetschin H, Cameron JS, Chantler C (1977) Prognosis of Henoch-Schonlein nephritis in children. Br Med J 2:11\u201314","journal-title":"Br Med J"},{"key":"6026_CR19","first-page":"S79","volume":"45","author":"DJ Nikolic-Paterson","year":"1994","unstructured":"Nikolic-Paterson DJ, Lan HY, Hill PA, Atkins RC (1994) Macrophages in renal injury. Kidney Int Suppl 45:S79-82","journal-title":"Kidney Int Suppl"},{"key":"6026_CR20","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/s00424-017-1942-x","volume":"469","author":"A Hammer","year":"2017","unstructured":"Hammer A, Stegbauer J, Linker RA (2017) Macrophages in neuroinflammation: role of the renin-angiotensin-system. Pflugers Arch 469:431\u2013444","journal-title":"Pflugers Arch"}],"container-title":["Pediatric Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00467-023-06026-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00467-023-06026-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00467-023-06026-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T11:08:22Z","timestamp":1695294502000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00467-023-06026-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,25]]},"references-count":20,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["6026"],"URL":"https:\/\/doi.org\/10.1007\/s00467-023-06026-5","relation":{},"ISSN":["0931-041X","1432-198X"],"issn-type":[{"value":"0931-041X","type":"print"},{"value":"1432-198X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,25]]},"assertion":[{"value":"26 December 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was performed according to the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of the University of Tokushima Graduate School.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consents were obtained from all participants.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The authors have no competing interests to declare that are relevant to the content of this article.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}