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The level of free light chain (FLC) that causes MCN varies substantially and there is uncertainty about the threshold level that should be used to inform clinical practice. In a multicentre cohort study of 103 patients with a diagnosis of MM and biopsy-confirmed MCN made between 2002\u20132014, we report prospectively measured levels of serum FLC at diagnosis obtained using a single nephelometric assay (Freelite\u00ae) and we explore the relationship between serum FLC level at diagnosis with renal outcome and patient survival. Using a landmark approach, overall survival (OS) was compared between patients who achieved independence from dialysis compared to those who remained dialysis dependent at 3-month, 6-month, 9-month, and 12-month time points. The median serum FLC level at diagnosis was 7531\u2009mg\/L (range 107\u2013114600). Serum creatinine was 535\u2009\u03bcmol\/L (range 168\u20132993) and eGFR 7\u2009ml\/min\/1.73\u2009m<jats:sup>2<\/jats:sup> (range 1\u201334). Six patients (5.8%) had an FLC level &lt;1500\u2009mg\/L, which is the International Myeloma Working Group threshold for MCN and two patients were below the International Kidney and Monoclonal Gammopathy working group threshold of 500\u2009mg\/L; one was hypercalcaemic, and one had high-normal serum calcium level and had received a non-steroidal anti-inflammatory agent. Sixty-nine (67%) patients required haemodialysis treatment of whom 36 (52.1%) recovered independent renal function. Sixty-six (64%) patients died with a median OS of 2.5 years (95% CI 1.8\u20133.3). A landmark analysis revealed that independence from dialysis was associated with improved survival at 3-months (<jats:italic>P<\/jats:italic>\u2009=\u20090.003), 6-months (<jats:italic>P<\/jats:italic>\u2009=\u20090.035) and 9-months (<jats:italic>P<\/jats:italic>\u2009=\u20090.014); there was no survival benefit observed beyond 12 months (<jats:italic>P<\/jats:italic>\u2009=\u20090.146). Serum FLC level at diagnosis was neither associated with renal function recovery nor with OS. This is the largest reported cohort of patients with biopsy-confirmed MCN and prospectively measured serum FLC levels. These results indicate that a serum monoclonal FLC\u2009&gt;\u2009500\u2009mg\/L should be considered the threshold level associated with the development of MCN.<\/jats:p>","DOI":"10.1038\/s41408-020-0295-4","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T16:49:28Z","timestamp":1583254168000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Serum free light chain level at diagnosis in myeloma cast nephropathy\u2014a multicentre study"],"prefix":"10.1038","volume":"10","author":[{"given":"Punit","family":"Yadav","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Insara Jaffer","family":"Sathick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5651-1411","authenticated-orcid":false,"given":"Nelson","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth E.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Cockwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,3]]},"reference":[{"key":"295_CR1","doi-asserted-by":"publisher","first-page":"9219","DOI":"10.1200\/JCO.2005.03.2086","volume":"23","author":"BM Augustson","year":"2005","unstructured":"Augustson, B. 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