Light Chain Proximal Tubulopathy: Clinical and Pathologic Characteristics in the Modern Treatment Era
Light Chain Proximal Tubulopathy: Clinical and Pathologic Characteristics in the Modern Treatment Era
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DOI：
10.1681/asn.2015020185
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发表时间：
2016-05-01
影响因子：
13.6
通讯作者：
D'Agati, Vivette D.
中科院分区：
文献类型：
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作者：
Stokes, Michael B.;Valeri, Anthony M.;D'Agati, Vivette D.
轻链近端肾小管病 (LCPT) 的特征是近端肾小管细胞内胞浆内含有单克隆 LC。结晶性 LCPT 与非结晶性 LCPT 的意义以及现代疗法的效果尚不清楚。我们报告了 2000 年至 2014 年间诊断的 40 名结晶性 LCPT 患者和 6 名非结晶性 LCPT 患者的临床病理特征。所有结晶性 LCPT 均为 K 限制性并表现出急性肾小管损伤。三分之一的非结晶性 LCPT 患者表现出 A 限制或急性肾小管损伤。只有结晶 LCPT 经常需要抗原修复才能通过免疫荧光证明单克隆 LC。在 38 名患者中，有 5 名患者通过光学显微镜无法检测到晶体，但通过电子显微镜可以看到晶体。在活检前仅 15% 的患者患有血淋巴肿瘤，其中包括 21 种具有肾脏意义的单克隆丙种球蛋白病； 15 多发性骨髓瘤；七个闷烧性多发性骨髓瘤；和其他三种肿瘤。活检指征包括 Fanconi 综合征（38%；全部患有结晶性 LCPT）、肾功能不全（83%）和蛋白尿（98%）。对 30 名结晶性 LCPT 患者（75%）和所有 6 名非结晶性 LCPT 患者进行了随访，其中 11 名接受了干细胞移植，16 名仅接受化疗，9 名未接受治疗。 22 名接受治疗的结晶性 LCPT 患者中有 6 名出现完全或非常好的部分血液学缓解。通过多变量分析，最终 eGFR 的唯一独立预测因子是初始 eGFR，这凸显了早期检测的重要性。所有接受干细胞移植治疗的结晶性 LCPT 患者的肾功能均稳定或改善，表明积极治疗对选定患者的有效性。
Light chain proximal tubulopathy (LCPT) is characterized by cytoplasmic inclusions of monoclonal LC within proximal tubular cells. The significance of crystalline versus noncrystalline LCPT and the effect of modern therapies are unknown. We reported the clinical-pathologic features of 40 crystalline and six noncrystalline LCPT patients diagnosed between 2000 and 2014. All crystalline LCPTs were K-restricted and displayed acute tubular injury. One-third of noncrystalline LCPT patients displayed A-restriction or acute tubular injury. Only crystalline LCPT frequently required antigen retrieval to demonstrate monoclonal LC by immunofluorescence. In five of 38 patients, crystals were not detectable by light microscopy, but they were visible by electron microscopy. Hematolymphoid neoplasms, known before biopsy in only 15% of patients, included 21 monoclonal gammopathies of renal significance; 15 multiple myelomas; seven smoldering multiple myelomas; and three other neoplasms. Biopsy indications included Fanconi syndrome (38%; all with crystalline LCPT), renal insufficiency (83%), and proteinuria (98%). Follow-up was available for 30 (75%) patients with crystalline LCPT and all six patients with noncrystalline LCPT, of whom 11 underwent stem cell transplant, 16 received chemotherapy only, and nine were untreated. Complete or very good partial hematologic remissions occurred in six of 22 treated crystalline LCPT patients. By multivariable analysis, the only independent predictor of final eGFR was initial eGFR, highlighting the importance of early detection. All patients with crystalline LCPT treated with stem cell transplant had stable or improved kidney function, indicating the effectiveness of aggressive therapy in selected patients.