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Serum free light chain level at diagnosis in myeloma cast nephropathy-a multicentre study.
Blood Cancer Journal ( IF 12.9 ) Pub Date : 2020-03-03 , DOI: 10.1038/s41408-020-0295-4 Punit Yadav 1, 2 , Insara Jaffer Sathick 3 , Nelson Leung 3 , Elizabeth E Brown 4 , Mark Cook 5 , Paul W Sanders 6, 7 , Paul Cockwell 1, 2
Blood Cancer Journal ( IF 12.9 ) Pub Date : 2020-03-03 , DOI: 10.1038/s41408-020-0295-4 Punit Yadav 1, 2 , Insara Jaffer Sathick 3 , Nelson Leung 3 , Elizabeth E Brown 4 , Mark Cook 5 , Paul W Sanders 6, 7 , Paul Cockwell 1, 2
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Myeloma cast nephropathy (MCN) is a common cause of severe renal impairment in multiple myeloma (MM). 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 2002-2014, we report prospectively measured levels of serum FLC at diagnosis obtained using a single nephelometric assay (Freelite®) 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 mg/L (range 107-114600). Serum creatinine was 535 μmol/L (range 168-2993) and eGFR 7 ml/min/1.73 m2 (range 1-34). Six patients (5.8%) had an FLC level <1500 mg/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 mg/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 1.8-3.3). A landmark analysis revealed that independence from dialysis was associated with improved survival at 3-months (P = 0.003), 6-months (P = 0.035) and 9-months (P = 0.014); there was no survival benefit observed beyond 12 months (P = 0.146). 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 > 500 mg/L should be considered the threshold level associated with the development of MCN.
中文翻译：
多发性骨髓瘤铸型肾病诊断中的血清游离轻链水平。
骨髓瘤铸型肾病（MCN）是多发性骨髓瘤（MM）中严重肾脏损害的常见原因。导致MCN的游离轻链（FLC）的水平变化很大，并且阈值水平存在不确定性，该阈值水平应用于指导临床实践。在2002年至2014年间对103例诊断为MM并经活检证实为MCN的患者进行的多中心队列研究中，我们报告了使用单一浊度法（Freelite®）获得的在诊断时预期测量的血清FLC水平，并探讨了两者之间的关系。诊断时的血清FLC水平与肾结局和患者生存率有关。使用具有里程碑意义的方法，比较了在3个月，6个月，9个月和12个月的时间点获得透析独立性的患者与仍然依赖透析的患者之间的总生存期（OS）。诊断时的血清FLC中位值为7531 mg / L（范围107-114600）。血清肌酐为535μmol/ L（范围168-2993）和eGFR 7 ml / min / 1.73 m2（范围1-34）。6名患者（5.8％）的FLC水平<1500 mg / L，这是国际骨髓瘤工作组对MCN的阈值，而2名患者低于国际肾脏病和单克隆Gammopathy工作组的阈值500 mg / L；一个是高钙血症的，另一个是血清钙水平高且接受非甾体类抗炎药。有69名（67％）患者需要血液透析治疗，其中36名（52.1％）患者恢复了独立的肾功能。六十六（64％）例患者死于中位OS为2.5年（95％CI为1.8-3.3）。一项具有里程碑意义的分析表明，独立于透析与3个月（P = 0.003），6个月（P = 0）的存活率提高相关。035）和9个月（P = 0.014）；超过12个月没有观察到生存获益（P = 0.146）。诊断时血清FLC水平与肾功能恢复或OS均无关。这是活检确诊的MCN和预期测量的血清FLC水平的最大患者队列。这些结果表明，血清单克隆FLC> 500 mg / L应被视为与MCN发生有关的阈值水平。
更新日期：2020-04-24
中文翻译：
多发性骨髓瘤铸型肾病诊断中的血清游离轻链水平。
骨髓瘤铸型肾病（MCN）是多发性骨髓瘤（MM）中严重肾脏损害的常见原因。导致MCN的游离轻链（FLC）的水平变化很大，并且阈值水平存在不确定性，该阈值水平应用于指导临床实践。在2002年至2014年间对103例诊断为MM并经活检证实为MCN的患者进行的多中心队列研究中，我们报告了使用单一浊度法（Freelite®）获得的在诊断时预期测量的血清FLC水平，并探讨了两者之间的关系。诊断时的血清FLC水平与肾结局和患者生存率有关。使用具有里程碑意义的方法，比较了在3个月，6个月，9个月和12个月的时间点获得透析独立性的患者与仍然依赖透析的患者之间的总生存期（OS）。诊断时的血清FLC中位值为7531 mg / L（范围107-114600）。血清肌酐为535μmol/ L（范围168-2993）和eGFR 7 ml / min / 1.73 m2（范围1-34）。6名患者（5.8％）的FLC水平<1500 mg / L，这是国际骨髓瘤工作组对MCN的阈值，而2名患者低于国际肾脏病和单克隆Gammopathy工作组的阈值500 mg / L；一个是高钙血症的，另一个是血清钙水平高且接受非甾体类抗炎药。有69名（67％）患者需要血液透析治疗，其中36名（52.1％）患者恢复了独立的肾功能。六十六（64％）例患者死于中位OS为2.5年（95％CI为1.8-3.3）。一项具有里程碑意义的分析表明，独立于透析与3个月（P = 0.003），6个月（P = 0）的存活率提高相关。035）和9个月（P = 0.014）；超过12个月没有观察到生存获益（P = 0.146）。诊断时血清FLC水平与肾功能恢复或OS均无关。这是活检确诊的MCN和预期测量的血清FLC水平的最大患者队列。这些结果表明，血清单克隆FLC> 500 mg / L应被视为与MCN发生有关的阈值水平。
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