{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T11:05:09Z","timestamp":1772708709790,"version":"3.50.1"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Nephrol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>TAFRO syndrome is a clinical subtype of idiopathic multicentric Castleman disease (iMCD) that is characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis (or renal dysfunction), and organomegaly. TAFRO syndrome has only recently been described, and many clinicians are unaware of this disease, leading to delays in diagnosis and treatment. We present two patients with TAFRO syndrome in whom renal biopsies were performed.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case presentation<\/jats:title>\n<jats:p>Both patients had subacute onset and exhibited renal insufficiency, edema, anemia, thrombocytopenia, polyserositis and lymphadenopathy over the disease course. However, there were many differences in their clinical manifestations. Case 1 was a 30-year-old woman admitted due to intermittent vaginal bleeding for 3\u2009weeks. Laboratory tests on admission showed severe renal insufficiency (creatinine: 624\u2009\u03bcmol\/L), severe anemia (Hb: 41\u2009g\/L), and moderate thrombocytopenia (61\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L). Case 2 was a 42-year-old man. Acute epigastric pain was his initial complaint, and computed tomography (CT) revealed retroperitoneal exudation around the pancreas. He was diagnosed with acute pancreatitis, and after treatment with a proton pump inhibitor (PPI) and somatostatin, his abdominal pain still recurred. During treatment, renal failure gradually increased, with oliguria, fever, anemia, thrombocytopenia, edema and massive ascites. Lymph node histologies were consistent with the hyaline-vascular (HV) type and mixed type, respectively, and renal histopathologies were consistent with thrombotic microangiopathy (TMA)-like renal lesions and membranoproliferative glomerulonephritis (MPGN), respectively. Their general conditions improved after glucocorticoid therapy, but their renal functions did not recover completely. On the basis of glucocorticoids, second-line treatments with tocilizumab and rituximab, respectively, were applied.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The diagnosis of TAFRO syndrome is based mainly on clinical manifestations and lymph node biopsies. A reliable early diagnosis and appropriate rapid treatment are essential to improve patient outcomes. Clinicians should deepen their understanding of this disease and similar conditions. Once the disease is suspected, lymph node biopsies should be performed as soon as possible. In addition, renal biopsies should be actively performed in patients with renal involvement.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12882-020-02119-7","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T11:04:15Z","timestamp":1606129455000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Kidney biopsy findings in two patients with TAFRO syndrome: case presentations and review of the literature"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0157-7752","authenticated-orcid":false,"given":"Qianyun","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangping","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"2119_CR1","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1002\/1097-0142(195607\/08)9:4<822::AID-CNCR2820090430>3.0.CO;2-4","volume":"9","author":"B Castleman","year":"1956","unstructured":"Castleman B, Iverson L, Menendez VP. Localized mediastinal lymph-node hyperplasia resembling thymoma. Cancer. 1956;9:822\u201330.","journal-title":"Cancer."},{"key":"2119_CR2","first-page":"119","volume":"12","author":"JA Flendrig","year":"1969","unstructured":"Flendrig JA, Schillings PHM. Benign giant lymphoma: the clinical signs and symptoms and the morphological aspects.y. Folia Med Neerl. 1969;12:119\u201320.","journal-title":"Folia Med Neerl"},{"issue":"3","key":"2119_CR3","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1097\/00000478-198304000-00001","volume":"7","author":"G Frizzera","year":"1983","unstructured":"Frizzera G, Banks PM, Massarelli G, Rosai J. A systemic lymphoproliferative disorder with morphologic features of Castleman\u2019s disease. Pathological findings in 15 patients. Am J Surg Pathol. 1983;7(3):211\u201331.","journal-title":"Am J Surg Pathol"},{"issue":"2","key":"2119_CR4","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S0046-8177(85)80065-4","volume":"16","author":"DD Weisenburger","year":"1985","unstructured":"Weisenburger DD, Nathwani BN, Winberg CD, Rappaport H. Multicentric angiofollicular lymph node hyperplasia: a clinicopathologicstudy of 16 cases. Hum Pathol. 1985;16(2):162\u201372.","journal-title":"Hum Pathol"},{"issue":"1","key":"2119_CR5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/ajcp\/83.1.27","volume":"83","author":"NA Lachant","year":"1985","unstructured":"Lachant NA, Sun NC, Leong LA, Oseas RS, Prince HE. Multicentric angiofollicular lymph node hyperplasia (Castleman\u2019s disease) followed by Kaposi\u2019s sarcoma in two homosexual males with the acquired immunodeficiency syndrome (AIDS). Am J Clin Pathol. 1985;83(1):27\u201333.","journal-title":"Am J Clin Pathol"},{"issue":"4","key":"2119_CR6","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1182\/blood.V86.4.1276.bloodjournal8641276","volume":"86","author":"J Soulier","year":"1995","unstructured":"Soulier J, Grollet L, Oksenhendler E, et al. Kaposi\u2019s sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman\u2019s disease. Blood. 1995;86(4):1276\u201380.","journal-title":"Blood."},{"key":"2119_CR7","doi-asserted-by":"publisher","first-page":"2924","DOI":"10.1182\/blood-2013-12-545087","volume":"123","author":"DC Fajgenbaum","year":"2014","unstructured":"Fajgenbaum DC, van Rhee F, Nabel CS. HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood. 2014;123:2924\u201333.","journal-title":"Blood"},{"key":"2119_CR8","first-page":"320","volume":"51","author":"K Takai","year":"2010","unstructured":"Takai K, Nikkuni K, Shibuya H, Hashidate H. [Thrombocytopenia with mild bone marrow fibrosis accompanied by fever, pleural effusion, ascites and hepatosplenomegaly]. [Rinsho ketsueki]. Jpn J Clin Hematol. 2010;51:320\u20135.","journal-title":"Jpn J Clin Hematol"},{"key":"2119_CR9","doi-asserted-by":"publisher","first-page":"95","DOI":"10.3960\/jslrt.53.95","volume":"53","author":"M Inoue","year":"2013","unstructured":"Inoue M, Ankou M, Hua J, Iwaki Y, Hagihara M. Complete resolution of TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulinfibrosis and organomegaly) after immunosuppressive therapies using corticosteroids and cyclosporin a: A case report. J Clin Exp Hematop. 2013;53:95\u20139.","journal-title":"J Clin Exp Hematop"},{"key":"2119_CR10","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3960\/jslrt.53.87","volume":"53","author":"N Iwaki","year":"2013","unstructured":"Iwaki N, Sato Y, Takata K, et al. Atypical hyaline vascular-type castleman\u2019s disease with thrombocytopenia, anasarca, fever, and systemic lymphadenopathy. J Clin Exp Hematop. 2013;53:87\u201393.","journal-title":"J Clin Exp Hematop"},{"key":"2119_CR11","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.2169\/internalmedicine.52.9482","volume":"52","author":"H Kawabata","year":"2013","unstructured":"Kawabata H, Kotani S, Matsumura Y, et al. Successful treatment of a patient with multicentric Castleman\u2019s disease who presented with thrombocytopenia, ascites, renal failure and myelofibrosis using tocilizumab, an anti-interleukin-6 receptor antibody. Intern Med. 2013;52:1503\u20137.","journal-title":"Intern Med"},{"key":"2119_CR12","doi-asserted-by":"publisher","first-page":"79","DOI":"10.3960\/jslrt.53.79","volume":"53","author":"Y Masaki","year":"2013","unstructured":"Masaki Y, Nakajima A, Iwao H, et al. Japanese variant of multicentric castleman\u2019s disease associated with serositis and thrombocytopenia\u2014Areport of two cases: is TAFRO syndrome (Castleman- Kojima disease) a distinct clinicopathological entity? J Clin Exp Hematop. 2013;53:79\u201385.","journal-title":"J Clin Exp Hematop"},{"key":"2119_CR13","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3960\/jslrt.53.63","volume":"53","author":"K Takai","year":"2013","unstructured":"Takai K, Nikkuni K, Momoi A, et al. Thrombocytopenia with reticulin fibrosis accompanied by fever, anasarca and hepatosplenomegaly: a clinical report of five cases. J Clin Exp Hematop. 2013;53:63\u20138.","journal-title":"J Clin Exp Hematop"},{"key":"2119_CR14","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3960\/jslrt.53.101","volume":"53","author":"N Awano","year":"2013","unstructured":"Awano N, Inomata M, Sonoda Y, et al. A case of multicentric castleman\u2019s disease of mixedtype, which showed constellation of symptoms,i.e., thrombocytopenia, anasarca, anemia, fever,myelofibrosis, and lymphadenopathy. J Clin Exp Hematop. 2013;53:101\u20135.","journal-title":"J Clin Exp Hematop"},{"issue":"2","key":"2119_CR15","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1002\/ajh.24242","volume":"91","author":"N Iwaki","year":"2016","unstructured":"Iwaki N, Fajgenbaum DC, Nabel CS, et al. Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease. Am J Hematol. 2016;91(2):220\u20136.","journal-title":"Am J Hematol"},{"key":"2119_CR16","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1007\/s12185-016-1979-1","volume":"103","author":"Y Masaki","year":"2016","unstructured":"Masaki Y, Kawabata H, Takai K, Kojima M, Tsukamoto N, Ishigaki Y, et al. Proposed diagnostic criteria, disease severity classification and treatment strategy for TAFRO syndrome, 2015 version. Int J Hematol. 2016;103:686\u201392.","journal-title":"Int J Hematol"},{"key":"2119_CR17","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1093\/ndt\/gfq427","volume":"26","author":"K El Karoui","year":"2011","unstructured":"El Karoui K, Vuiblet V, Dion D, et al. Renal involvement in Castleman disease. Nephrol Dial Transplant. 2011;26:599\u2013609.","journal-title":"Nephrol Dial Transplant"},{"issue":"supple 3","key":"2119_CR18","doi-asserted-by":"publisher","first-page":"iii119","DOI":"10.1093\/ndt\/gfr245","volume":"27","author":"D Xu","year":"2012","unstructured":"Xu D, Lv J, Dong Y, et al. Renal involvement in a large cohort of chinese patients with Castleman disease. Nephrol Dial Transplant. 2012;27(supple 3):iii119\u201325.","journal-title":"Nephrol Dial Transplant"},{"issue":"6","key":"2119_CR19","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.3109\/14397595.2015.1059982","volume":"27","author":"M Kawashima","year":"2017","unstructured":"Kawashima M, Usui T, Okada H, et al. TAFRO syndrome: 2 cases and review of the literature. Mod Rheumatol. 2017;27(6):1093\u20137.","journal-title":"Mod Rheumatol"},{"issue":"24","key":"2119_CR20","doi-asserted-by":"publisher","first-page":"e1 1057","DOI":"10.1097\/MD.0000000000011057","volume":"97","author":"Y Furuto","year":"2018","unstructured":"Furuto Y, Hashimoto H, Horiuti H, Shibuya Y. Membranoproliferative glomerulonephritis-like findings for TAFRO syndrome, associated with ananterior mediastinal tumor : a case report. Medicine (Baltimore). 2018;97(24):e1 1057.","journal-title":"Medicine (Baltimore)"},{"issue":"21","key":"2119_CR21","doi-asserted-by":"publisher","first-page":"3129","DOI":"10.2169\/internalmedicine.0806-18","volume":"57","author":"S Ito","year":"2018","unstructured":"Ito S, Uchida T, Itai H, et al. Serial manifestation of acute kidney injury and nephrotic syndrome in a patient with TAFRO syndrome. Intern Med. 2018;57(21):3129\u201333.","journal-title":"Intern Med"},{"issue":"1","key":"2119_CR22","doi-asserted-by":"publisher","first-page":"16","DOI":"10.5414\/CNCS109400","volume":"6","author":"Y Noda","year":"2018","unstructured":"Noda Y, Saka Y, Kato A, Mimura T, Naruse T. Successful rituximab treatment of TAFRO syndrome with pathological findings of glomerular endothelial damage. Clin Nehrol Case Stud. 2018;6(1):16\u201320.","journal-title":"Clin Nehrol Case Stud"},{"issue":"40","key":"2119_CR23","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000008216","volume":"96","author":"M Tanaka","year":"2017","unstructured":"Tanaka M, Tsujimoto H, Yamamoto K, Shimoda S, Oka K, Takeoka H. Clinicopathological features of progressive renal involvement in TAFRO syndrome: a case report and literature review. Medicine (Baltimore). 2017;96(40):e8216.","journal-title":"Medicine (Baltimore)"},{"issue":"13","key":"2119_CR24","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000006271","volume":"96","author":"FF Jose","year":"2017","unstructured":"Jose FF, Kerbauy LN, Perini GF, et al. A life-threatening case of TAFRO syndrome with dramatic response to tocilizumab, rituximab, and pulse steroids: the first case report in Latin America. Medicine (Baltimore). 2017;96(13):e6271.","journal-title":"Medicine (Baltimore)"},{"issue":"1","key":"2119_CR25","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1007\/s13730-018-0319-0","volume":"7","author":"S Noda-Narita","year":"2018","unstructured":"Noda-Narita S, Sumida K, Sekine A, et al. TAFRO syndrome with refractory thrombocytopenia responding to tocilizumab and romiplostim: a case report. CEN Case Rep. 2018;7(1):162\u20138.","journal-title":"CEN Case Rep."},{"issue":"2","key":"2119_CR26","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/s13730-018-0338-x","volume":"7","author":"T Ozeki","year":"2018","unstructured":"Ozeki T, Tsuji M, Yamamoto J, Shigematsu C, Maruyama S. Thrombotic microangiopathy on kidney biopsy in a patient with TAFRO syndrome. CEN Case Rep. 2018;7(2):243\u20137.","journal-title":"CEN Case Rep"},{"key":"2119_CR27","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.humpath.2018.03.021","volume":"82","author":"H Mizuno","year":"2018","unstructured":"Mizuno H, Sekine A, Oguro M, et al. Renal histology in a patient with TAFRO syndrome: a case report. Hum Pathol. 2018;82:258\u201363.","journal-title":"Hum Pathol"},{"issue":"8","key":"2119_CR28","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.2169\/internalmedicine.9556-17","volume":"57","author":"A Nakamori","year":"2018","unstructured":"Nakamori A, Akagaki F, Yamaguchi Y, Arima R, Sugiura T. Nephrotic syndrome with thrombocytopenia, lymphadenopathy, systemic inflammation, and splenomegaly. Intern Med. 2018;57(8):1123\u20139.","journal-title":"Intern Med"},{"key":"2119_CR29","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1038\/nrneph.2014.217","volume":"11","author":"HT Cook","year":"2015","unstructured":"Cook HT, Pickering MC. Histopathology of MPGN and C3 glomerulopathies. Nat Rev Nephrol. 2015;11:14\u201322.","journal-title":"Nat Rev Nephrol"},{"key":"2119_CR30","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1160\/TH07-12-0761","volume":"101","author":"K Benz","year":"2009","unstructured":"Benz K, Amann K. Pathological aspects of membranoproliferative glomerulonephritis (MPGN) and haemolytic uraemic syndrome (HUS)\/thrombocytic thrombopenic purpura (TTP). Thromb Haemost. 2009;101:265\u201370.","journal-title":"Thromb Haemost"},{"key":"2119_CR31","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.3389\/fimmu.2019.01489","volume":"10","author":"A Leurs","year":"2019","unstructured":"Leurs A, Gnemmi V, Lionet A, et al. Renal pathologic findings in TAFRO syndrome: Is there a continuum between thrombotic microangiopathy and membranoproliferative glomerulonephritis? A case report and literature review. Front Immunol. 2019;10:1489.","journal-title":"Front Immunol"}],"container-title":["BMC Nephrology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12882-020-02119-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12882-020-02119-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12882-020-02119-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T11:13:29Z","timestamp":1606130009000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcnephrol.biomedcentral.com\/articles\/10.1186\/s12882-020-02119-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,23]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["2119"],"URL":"https:\/\/doi.org\/10.1186\/s12882-020-02119-7","relation":{},"ISSN":["1471-2369"],"issn-type":[{"value":"1471-2369","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,23]]},"assertion":[{"value":"11 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from all individual participants included in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no conflicts of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"499"}}