文章：

多发性骨髓瘤管型肾病诊断时的血清游离轻链水平——多中心研究

Serum free light chain level at diagnosis in myeloma cast nephropathy—a multicentre study

原文发布日期：2020-03-03

DOI: 10.1038/s41408-020-0295-4

类型: Article

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英文摘要：

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.
 

摘要翻译： 

骨髓瘤管型肾病（MCN）是多发性骨髓瘤（MM）患者发生严重肾功能损害的常见原因。引发MCN的游离轻链（FLC）水平存在显著差异，且用于指导临床实践的阈值水平尚未明确。在一项针对2002年至2014年间经活检确诊的103例MM合并MCN患者的多中心队列研究中，我们前瞻性采用单一比浊法检测（Freelite®）获取诊断时的血清FLC水平，并探讨其与肾脏结局及患者生存率的关系。通过界标分析法，比较了在3个月、6个月、9个月和12个月时间点脱离透析依赖的患者与持续依赖透析患者的总生存期（OS）。诊断时中位血清FLC水平为7531 mg/L（范围107-114600），血清肌酐为535 μmol/L（范围168-2993），估算肾小球滤过率（eGFR）为7 ml/min/1.73 m²（范围1-34）。6例（5.8%）患者FLC水平低于国际骨髓瘤工作组设定的MCN阈值1500 mg/L，其中2例低于国际肾脏与单克隆丙种球蛋白病工作组设定的500 mg/L阈值（1例伴高钙血症，1例血钙正常高值且曾服用非甾体抗炎药）。69例（67%）患者需要血液透析治疗，其中36例（52.1%）恢复独立肾功能。66例（64%）患者死亡，中位OS为2.5年（95%置信区间1.8-3.3）。界标分析显示，脱离透析依赖与3个月（P=0.003）、6个月（P=0.035）和9个月（P=0.014）的生存改善相关，但超过12个月后未观察到生存获益（P=0.146）。诊断时血清FLC水平与肾功能恢复及OS均无关联。本研究是迄今最大规模的经活检确诊MCN且前瞻性检测血清FLC水平的队列报告，结果表明血清单克隆FLC > 500 mg/L应被视为MCN发生的相关阈值水平。

原文链接：

Serum free light chain level at diagnosis in myeloma cast nephropathy—a multicentre study