{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:52:08Z","timestamp":1790790728884,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The mTORC1 pathway drives pathogenesis in autoimmune kidney diseases. We hypothesized that intrarenal mTORC1 activation could identify patients likely to benefit from sirolimus, irrespective of their specific diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective proof-of-concept series, we screened eight patients with active autoimmune kidney disease for mTORC1 activation by immunohistochemistry on renal biopsy. Five positive patients (staining intensity: + to +++) received sirolimus, presenting with lupus nephritis atypical hemolytic uremic syndrome (aHUS), thrombotic microangiopathy (TMA), or IgA nephropathy (IgAN) associated with lung cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Over a mean follow-up of 25\u00a0months, four patients exhibited improved or stable renal function. All responders demonstrated moderate-to-high (++ to +++) mTORC1 staining, whereas the single non-responder who progressed to end-stage renal disease had only weak (+) staining. Proteinuria declined to &amp;lt;1\u00a0g\/day in most responders. Sirolimus was well-tolerated. In two patients with concurrent malignancy, sirolimus did not aggravate stable breast cancer but was discontinued due to lung adenocarcinoma progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study indicates that intrarenal mTORC1 activation levels may help identify patients more likely to respond to sirolimus across various autoimmune kidney diseases, warranting further investigation as a precision-medicine approach.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1791188","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:03:47Z","timestamp":1785305027000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Sirolimus application in patients with autoimmune-associated kidney diseases based on mTORC1 activation: a preliminary exploration and future perspectives"],"prefix":"10.3389","volume":"17","author":[{"given":"Chuanchuan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Nephrology, Peking University International Hospital","place":["Beijing, China"]},{"name":"School of Public Health, Peking University","place":["Beijing, China"]},{"name":"National Institute of Health Data Science, Peking University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wan","sequence":"additional","affiliation":[{"name":"Nephrology Rehabilitation Center, Beijing Zhongguancun Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Peking University People\u2019s Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Peking University International Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Peking University International Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1007\/s00467-016-3474-6","article-title":"Treatment of renal angiomyolipoma in tuberous sclerosis complex (TSC) patients","volume":"32","author":"Brakemeier","year":"2017","journal-title":"Pediatr. 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