{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:53:31Z","timestamp":1792788811062,"version":"4.5.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","funder":[{"DOI":"10.13039\/501100018605","name":"Guangzhou Regenerative Medicine and Health Guangdong Laboratory","doi-asserted-by":"publisher","award":["2018GZR0201003"],"award-info":[{"award-number":["2018GZR0201003"]}],"id":[{"id":"10.13039\/501100018605","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Provincial Key Laboratory of Renal Failure Research","award":["2017B030314036"],"award-info":[{"award-number":["2017B030314036"]}]},{"name":"National Innovation Team Program","award":["81521003"],"award-info":[{"award-number":["81521003"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>The lack of a tool for predicting the response to immunosuppressive therapy in IgA nephropathy (IgAN) limits patient-specific risk stratification and early treatment decisions. To derive and validate the models for predicting response to immunosuppressive therapy in IgAN that can be applied at the time of kidney biopsy, the authors conducted a prospective cohort study of 621 Chinese patients with IgAN. Patients had persistent proteinuria of \u22651 g\/d, despite 3 months of optimized supportive care with renin-angiotensin system inhibitors, and received immunosuppressive therapy. The authors used immunohistochemistry to identify cellular infiltrates in biopsy specimens and digital image analysis to quantify them. The intensity of glomerular macrophage infiltration, alone or combined with clinical and histologic data, accurately predicted the response to immunosuppression and, thus, may help physicians identify patients with IgAN who will benefit from immunosuppression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The lack of a tool for predicting the response to immunosuppressive therapy in IgA nephropathy (IgAN) limits patient-specific risk stratification and early treatment decision making. Models for predicting response to immunosuppression in IgAN that can be applied at the time of kidney biopsy are needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective cohort study involved 621 Chinese patients with IgAN who were at high risk for disease progression and had persistent proteinuria \u22651 g\/d, despite 3 months of optimized supportive care with renin-angiotensin system inhibitors. Participants received immunosuppressive therapy for a median of 18 months. We used immunochemistry to identify macrophage and lymphocyte infiltrates in biopsy specimens and digital image analysis to quantify them. The outcome was response to immunosuppression, defined as complete or partial remission within 12 months of immunosuppression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Kidney infiltration of CD68\n                      <jats:sup>+<\/jats:sup>\n                      and CD206\n                      <jats:sup>+<\/jats:sup>\n                      macrophages increased in patients with IgAN. Having higher levels of glomerular CD206\n                      <jats:sup>+<\/jats:sup>\n                      macrophage infiltration was associated with a 40-fold increased probability of response to immunosuppression in adjusted analysis compared with having lower levels. Patients with a higher intensity of glomerular CD68\n                      <jats:sup>+<\/jats:sup>\n                      infiltrates had a 13-fold increase in probability of responding to immunosuppression. Intensity of glomerular CD206\n                      <jats:sup>+<\/jats:sup>\n                      and CD68\n                      <jats:sup>+<\/jats:sup>\n                      macrophage infiltration predicted the response to immunosuppression (area under the curve [AUC], 0.84; 95% CI, 0.81 to 0.88). The AUC increased to 0.87 (95% CI, 0.84 to 0.91) in a model combining the infiltration score of CD206\n                      <jats:sup>+<\/jats:sup>\n                      and CD68\n                      <jats:sup>+<\/jats:sup>\n                      infiltrates with the MEST-C score and clinical data at biopsy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Intensity of glomerular macrophage infiltration predicted response to immunosuppressive therapy in patients with IgAN who were at high risk of progression, and may help physicians identify patients who will benefit from such treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2021060815","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T13:52:32Z","timestamp":1634737952000},"page":"3187-3196","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":63,"title":["Intensity of Macrophage Infiltration in Glomeruli Predicts Response to Immunosuppressive Therapy in Patients with IgA Nephropathy"],"prefix":"10.1681","volume":"32","author":[{"given":"Di","family":"Xie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6324-5211","authenticated-orcid":false,"given":"Xin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanmei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cailing","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4740-805X","authenticated-orcid":false,"given":"Youhua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan Fan","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,12]]},"reference":[{"key":"B1-20240826","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1056\/NEJMra1206793","article-title":"IgA nephropathy","volume":"368","author":"Wyatt","year":"2013","journal-title":"N Engl J Med"},{"key":"B2-20240826","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/0002-9343(90)90300-3","article-title":"A retrospective analysis of the natural history of primary IgA nephropathy worldwide","volume":"89","author":"Schena","year":"1990","journal-title":"Am J Med"},{"key":"B3-20240826","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1038\/sj.ki.5002185","article-title":"Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels","volume":"71","author":"Moldoveanu","year":"2007","journal-title":"Kidney Int"},{"key":"B4-20240826","first-page":"1668","article-title":"Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity","volume":"119","author":"Suzuki","year":"2009","journal-title":"J Clin Invest"},{"key":"B5-20240826","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev-pathol-011110-130216","article-title":"IgA nephropathy: Molecular mechanisms of the disease","volume":"8","author":"Mestecky","year":"2013","journal-title":"Annu Rev Pathol"},{"key":"B6-20240826","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/ki.2015.252","article-title":"New developments in the genetics, pathogenesis, and therapy of IgA nephropathy","volume":"88","author":"Magistroni","year":"2015","journal-title":"Kidney Int"},{"key":"B7-20240826","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1056\/NEJMoa1415463","article-title":"Intensive supportive care plus immunosuppression in IgA nephropathy","volume":"373","author":"Rauen","year":"2015","journal-title":"N Engl J Med"},{"key":"B8-20240826","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1681\/ASN.2017060713","article-title":"Effects of two immunosuppressive treatment protocols for IgA nephropathy","volume":"29","author":"Rauen","year":"2018","journal-title":"J Am Soc Nephrol"},{"key":"B9-20240826","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.kint.2020.04.046","article-title":"After ten years of follow-up, no difference between supportive care plus immunosuppression and supportive care alone in IgA nephropathy","volume":"98","author":"Rauen","year":"2020","journal-title":"Kidney Int"},{"key":"B10-20240826","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1111\/j.1523-1755.2005.00460.x","article-title":"Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy","volume":"68","author":"Tang","year":"2005","journal-title":"Kidney Int"},{"key":"B11-20240826","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1001\/jama.2017.9362","article-title":"Effect of oral methylprednisolone on clinical outcomes in patients with IgA nephropathy: The TESTING Randomized Clinical Trial","volume":"318","author":"Lv","year":"2017","journal-title":"JAMA"},{"key":"B12-20240826","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1016\/S0140-6736(17)30550-0","article-title":"Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): A double-blind, randomised, placebo-controlled phase 2b trial","volume":"389","author":"Fellstr\u00f6m","year":"2017","journal-title":"Lancet"},{"key":"B13-20240826","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1053\/j.ajkd.2019.01.026","article-title":"Effects of hydroxychloroquine on proteinuria in IgA nephropathy: A randomized controlled trial","volume":"74","author":"Liu","year":"2019","journal-title":"Am J Kidney Dis"},{"key":"B16-20240826","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/ki.2009.243","article-title":"The Oxford classification of IgA nephropathy: Rationale, clinicopathological correlations, and classification","volume":"76","author":"Cattran","year":"2009","journal-title":"Kidney Int"},{"key":"B17-20240826","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1001\/jamainternmed.2019.0600","article-title":"Evaluating a new international risk-prediction tool in IgA nephropathy","volume":"179","author":"Barbour","year":"2019","journal-title":"JAMA Intern Med"},{"key":"B18-20240826","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.2215\/CJN.11521210","article-title":"Pathologic predictors of renal outcome and therapeutic efficacy in IgA nephropathy: Validation of the oxford classification","volume":"6","author":"Shi","year":"2011","journal-title":"Clin J Am Soc Nephrol"},{"key":"B19-20240826","first-page":"CD003965","article-title":"Immunosuppressive agents for treating IgA nephropathy","volume":"3","author":"Natale","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"key":"B20-20240826","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1053\/j.ajkd.2019.07.018","article-title":"Urinary matrix metalloproteinase 7 and prediction of IgA nephropathy progression","volume":"75","author":"Yang","year":"2020","journal-title":"Am J Kidney Dis"},{"key":"B21-20240826","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/oxfordjournals.ndt.a091854","article-title":"The role of interstitial infiltrates in IgA nephropathy: A study with monoclonal antibodies","volume":"4","author":"Alexopoulos","year":"1989","journal-title":"Nephrol Dial Transplant"},{"key":"B22-20240826","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/ki.1991.82","article-title":"Significance of mononuclear phagocytes in IgA nephropathy","volume":"39","author":"Arima","year":"1991","journal-title":"Kidney Int"},{"key":"B23-20240826","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1093\/ckj\/sft004","article-title":"Clinicopathological and immunohistological features in childhood IgA nephropathy: A single-centre experience","volume":"6","author":"Topaloglu","year":"2013","journal-title":"Clin Kidney J"},{"key":"B24-20240826","doi-asserted-by":"crossref","first-page":"181","DOI":"10.5858\/133.2.181","article-title":"The renal biopsy","volume":"133","author":"Walker","year":"2009","journal-title":"Arch Pathol Lab Med"},{"key":"B25-20240826","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1681\/ASN.2006121372","article-title":"Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: A randomized controlled study of benazepril and losartan in chronic renal insufficiency","volume":"18","author":"Hou","year":"2007","journal-title":"J Am Soc Nephrol"},{"key":"B26-20240826","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/labinvest.2014.90","article-title":"Renal expression of advanced oxidative protein products predicts progression of renal fibrosis in patients with IgA nephropathy","volume":"94","author":"Wang","year":"2014","journal-title":"Lab Invest"},{"key":"B27-20240826","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/his.13768","article-title":"Relationship between renal CD68+ infiltrates and the Oxford Classification of IgA nephropathy","volume":"74","author":"Soares","year":"2019","journal-title":"Histopathology"},{"key":"B28-20240826","doi-asserted-by":"crossref","first-page":"16569","DOI":"10.1073\/pnas.0507655102","article-title":"An index to quantify an individual\u2019s scientific research output","volume":"102","author":"Hirsch","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B29-20240826","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/j.kint.2017.02.003","article-title":"Oxford Classification of IgA nephropathy 2016: An update from the IgA Nephropathy Classification Working Group","volume":"91","author":"Trimarchi","year":"2017","journal-title":"Kidney Int"},{"key":"B30-20240826","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"B31-20240826","doi-asserted-by":"crossref","first-page":"55","DOI":"10.7326\/M14-0697","article-title":"Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): The TRIPOD statement","volume":"162","author":"Collins","year":"2015","journal-title":"Ann Intern Med"},{"key":"B32-20240826","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0272-6386(12)81011-0","article-title":"IgA nephropathy: Morphologic expression and pathogenesis","volume":"23","author":"Emancipator","year":"1994","journal-title":"Am J Kidney Dis"},{"key":"B33-20240826","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/sj.ki.5002046","article-title":"Severity of tubulointerstitial inflammation and prognosis in immunoglobulin A nephropathy","volume":"71","author":"Myllym\u00e4ki","year":"2007","journal-title":"Kidney Int"},{"key":"B34-20240826","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1081\/JDI-100104732","article-title":"Role of proteinuria reduction in the progression of IgA nephropathy","volume":"23","author":"Locatelli","year":"2001","journal-title":"Ren Fail"},{"key":"B35-20240826","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/S0272-6386(00)70326-X","article-title":"Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy","volume":"35","author":"Shoji","year":"2000","journal-title":"Am J Kidney Dis"},{"key":"B36-20240826","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41581-019-0110-2","article-title":"Macrophages: Versatile players in renal inflammation and fibrosis","volume":"15","author":"Tang","year":"2019","journal-title":"Nat Rev Nephrol"},{"key":"B37-20240826","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1084\/jem.147.2.369","article-title":"A mononuclear cell component in experimental immunological glomerulonephritis","volume":"147","author":"Schreiner","year":"1978","journal-title":"J Exp Med"},{"key":"B38-20240826","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1016\/j.ajpath.2016.08.012","article-title":"Transfusion of CD206+ M2 macrophages ameliorates antibody-mediated glomerulonephritis in mice","volume":"186","author":"Du","year":"2016","journal-title":"Am J Pathol"},{"key":"B39-20240826","first-page":"1322","article-title":"Macrophages in diabetic nephropathy in patients with type 2 diabetes","volume":"32","author":"Klessens","year":"2017","journal-title":"Nephrol Dial Transplant"},{"key":"B40-20240826","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jaut.2014.11.007","article-title":"Macrophage depletion ameliorates nephritis induced by pathogenic antibodies","volume":"57","author":"Chalmers","year":"2015","journal-title":"J Autoimmun"},{"key":"B41-20240826","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1111\/nep.12232","article-title":"Resistance factors for the treatment of immunoglobulin A nephropathy with diffuse mesangial proliferation","volume":"19","author":"Kawasaki","year":"2014","journal-title":"Nephrology (Carlton)"},{"key":"B42-20240826","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1053\/ajkd.2002.31399","article-title":"Regression of IgA nephropathy: A repeat biopsy study","volume":"39","author":"Hotta","year":"2002","journal-title":"Am J Kidney Dis"},{"key":"B43-20240826","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s10157-004-0298-7","article-title":"The effectiveness of steroid therapy for patients with advanced IgA nephropathy and impaired renal function","volume":"8","author":"Moriyama","year":"2004","journal-title":"Clin Exp Nephrol"},{"key":"B44-20240826","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s10157-020-01918-4","article-title":"Efficacy of corticosteroid therapy for IgA nephropathy patients stratified by kidney function and proteinuria","volume":"24","author":"Nagasawa","year":"2020","journal-title":"Clin Exp Nephrol"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.2021060815","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:25:41Z","timestamp":1786130741000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.2021060815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":42,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2021060815","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"2021-06-17","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-30","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}