{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T03:50:47Z","timestamp":1782791447324,"version":"3.54.5"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/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>Thrombotic microangiopathy (TMA) is a histopathological entity associated with microangiopathic hemolytic anemia, thrombocytopenia, and end-organ ischemic damage. Although TMA is caused by various diseases, there have been few reports regarding children with idiopathic nephrotic syndrome (NS) and TMA. Here we report two 1-year-old infants with steroid-resistant NS (SRNS) who presented with severe hypertension, acute kidney injury (AKI), and TMA.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case presentation<\/jats:title>\n<jats:p>The diagnosis of NS was complicated with anemia, AKI, and hypertension. Maximum blood pressure was 150\/70\u2009mmHg in Case 1 and 136\/86\u2009mmHg in Case 2. There was no thrombocytopenia during their clinical course in both cases. Renal biopsy showed the features of TMA, including endothelial cell swelling, capillarectasia or marked mesangiolysis, along with mesangial proliferation in Case 1 and TMA with minor glomerular abnormalities in Case 2. Hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and secondary TMA other than that caused by hypertension were excluded. Oral prednisolone therapy, frequent infusion of albumin and diuretics, and multiple anti-hypertensive drugs were initiated. Blood pressure was controlled after 6 and 7\u2009days from initiation of multiple anti-hypertensive drugs and lisinopril was added due to persistent mild proteinuria and mild hypertension after improvement of renal function in both cases. Proteinuria resolved completely 4\u2009months after admission with daily oral prednisolone for 4\u2009weeks followed by alternative daily oral prednisolone for 4\u2009weeks in Case 1. Proteinuria resolved completely 10\u2009months after admission with initial prednisolone treatment for 4\u2009weeks followed by cyclosporine A and intravenous methylprednisolone pulse therapy in Case 2. The follow-up biopsy showed no TMA findings in both patients. Because the patient in Case 1 subsequently developed frequent relapsing NS, cyclosporine A was commenced after the second biopsy and he did not have any flares for 2\u2009years. Renal function was normal in Case 1 and mildly decreased in Case 2 at last follow-up (creatinine-eGFR of 136.2\u2009mL\/min\/cm<jats:sup>2<\/jats:sup> in Case 1 and 79.5\u2009mL\/min\/cm<jats:sup>2<\/jats:sup> in Case 2).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Severe hypertension and AKI can be signs of TMA in patients with SRNS. Strict anti-hypertensive therapy might improve renal outcomes.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12882-020-01985-5","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T12:06:34Z","timestamp":1596456394000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Two cases of idiopathic steroid-resistant nephrotic syndrome complicated with thrombotic microangiopathy"],"prefix":"10.1186","volume":"21","author":[{"given":"Kentaro","family":"Nishi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Ogura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Okutsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Ishikura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3528-6961","authenticated-orcid":false,"given":"Koichi","family":"Kamei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,3]]},"reference":[{"key":"1985_CR1","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.1093\/ndt\/gfs279","volume":"27","author":"T Barbour","year":"2012","unstructured":"Barbour T, Johnson S, Cohney S, Hughes P. Thrombotic microangiopathy and associated renal disorders. Nephrol Dial Transplant. 2012;27:2673\u201385.","journal-title":"Nephrol Dial Transplant"},{"key":"1985_CR2","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1007\/s00467-007-0563-6","volume":"22","author":"K Benz","year":"2007","unstructured":"Benz K, Amann K, Dittrich K, Dotsch J. Thrombotic microangiopathy as a complication in a patient with focal segmental glomerulosclerosis. Pediatr Nephrol. 2007;22:2125\u20138.","journal-title":"Pediatr Nephrol"},{"key":"1985_CR3","doi-asserted-by":"crossref","unstructured":"The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr. 1981;98:561\u20134.","DOI":"10.1016\/S0022-3476(81)80760-3"},{"key":"1985_CR4","first-page":"680502","volume":"2014","author":"XJ Yu","year":"2014","unstructured":"Yu XJ, Yu F, Song D, Wang SX, Song Y, Liu G, et al. Clinical and renal biopsy findings predicting outcome in renal thrombotic microangiopathy: a large cohort study from a single institute in China. Scientific World J. 2014;2014:680502.","journal-title":"Scientific World J"},{"key":"1985_CR5","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1291\/hypres.31.479","volume":"31","author":"B Zhang","year":"2008","unstructured":"Zhang B, Xing C, Yu X, Sun B, Zhao X, Qian J. Renal thrombotic microangiopathies induced by severe hypertension. Hypertension Res. 2008;31:479\u201383.","journal-title":"Hypertension Res"},{"key":"1985_CR6","doi-asserted-by":"publisher","first-page":"e20171904","DOI":"10.1542\/peds.2017-1904","volume":"140","author":"JT Flynn","year":"2017","unstructured":"Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, et al. Clinical practice guideline for screening and Management of High Blood Pressure in children and adolescents. Pediatrics. 2017;140:e20171904.","journal-title":"Pediatrics."},{"key":"1985_CR7","first-page":"352","volume":"10","author":"RO Mathew","year":"2016","unstructured":"Mathew RO, Nayer A, Asif A. The endothelium as the common denominator in malignant hypertension and thrombotic microangiopathy. JASH. 2016;10:352\u20139.","journal-title":"JASH."},{"key":"1985_CR8","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/0300-2977(94)00061-D","volume":"46","author":"EH Ie","year":"1995","unstructured":"Ie EH, Karschner JK, Shapiro AP. Reversible nephrotic syndrome due to high renin state in renovascular hypertension. Neth J Med. 1995;46:136\u201341.","journal-title":"Neth J Med"},{"key":"1985_CR9","doi-asserted-by":"publisher","first-page":"287","DOI":"10.3389\/fped.2019.00287","volume":"7","author":"IF Shatat","year":"2019","unstructured":"Shatat IF, Becton LJ, Woroniecki RP. Hypertension in childhood Nephrotic syndrome. Front Pediatr. 2019;7:287.","journal-title":"Front Pediatr"},{"key":"1985_CR10","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1007\/s00467-006-0413-y","volume":"22","author":"IF Shatat","year":"2007","unstructured":"Shatat IF, Schoeneman M, Flynn JT, Woroniecki RP. Association of steroid and cyclosporin resistance in focal segmental glomerulosclerosis. Pediatr Nephrol. 2007;22:834\u20139.","journal-title":"Pediatr Nephrol"},{"key":"1985_CR11","doi-asserted-by":"crossref","unstructured":"Sato M, Ishikura K, Ando T, Kikunaga K, Terano C, Hamada R, et al. Prognosis and acute complications at the first onset of idiopathic nephrotic syndrome in children: a nationwide survey in Japan (JP-SHINE study). Nephrol Dial Transplant. 2019. [Online ahead of print].","DOI":"10.1093\/ndt\/gfz185"},{"key":"1985_CR12","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1016\/j.kint.2016.12.009","volume":"91","author":"SAMGE Timmermans","year":"2017","unstructured":"Timmermans SAMGE, Abdul-Hamid MA, Vanderlocht J, Damoiseaux JGMC, Reutelingsperger CP, van Paassen P, et al. Patients with hypertension-associated thrombotic microangiopathy may present with complement abnormalities. Kidney Int. 2017;91:1420\u20135.","journal-title":"Kidney Int"},{"key":"1985_CR13","doi-asserted-by":"publisher","first-page":"2234","DOI":"10.1681\/ASN.2018020184","volume":"29","author":"SAMGE Timmermans","year":"2018","unstructured":"Timmermans SAMGE, Abdul-Hamid MA, Potjewijd J, Theunissen ROMFIH, Damoiseaux JGMC, Reutelingsperger CP, et al. C5b9 formation on endothelial cells reflects complement defects among patients with renal thrombotic Microangiopathy and severe hypertension. J Am Soc Nephrol. 2018;29:2234\u201343.","journal-title":"J Am Soc Nephrol"}],"container-title":["BMC Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12882-020-01985-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12882-020-01985-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12882-020-01985-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T23:21:29Z","timestamp":1627946489000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcnephrol.biomedcentral.com\/articles\/10.1186\/s12882-020-01985-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,3]]},"references-count":13,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1985"],"URL":"https:\/\/doi.org\/10.1186\/s12882-020-01985-5","relation":{},"ISSN":["1471-2369"],"issn-type":[{"value":"1471-2369","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,3]]},"assertion":[{"value":"20 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethics approval was not applicable. Informed consent was obtained from all individual participants included in this report.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent for publication was obtained from all individual guardians included in this report. Written informed consent was obtained from the legal guardians as participants were under 16\u2009years old. This was for all potentially identifiable information contained within the manuscript file and that this is available for review by the editor of the journal.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Koichi Kamei has received research funding from the Terumo Foundation for Life Sciences and Arts, and donations from Ono Pharmaceutical Co., Ltd. Kenji Ishikura has received lecture fees from Asahi Kasei Pharma, Chugai Pharmaceutical Co. Ltd., Zenyaku Kogyo Co., Ltd., Novartis Pharma K.K. and grants from Asahi Kasei Pharma, Chugai Pharmaceutical Co., Ltd., Novartis Pharma, and Zenyaku Kogyo Co., Ltd. The other authors have no potential conflicts of interest to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"323"}}