Lin Yao, Xing Guolan, Hu Ruimin, Liu Shaojun, Li Guisen, Zhang Ping, Xu Feng, Liang Dandan, Zhu Xiaodong, Zhang Mingchao, Yang Fan, Yao Xinchen, Liu Feng, Wang Yujie, Dong Shihui, Liang Shaoshan, Zeng Caihong
National Clinical Research Center for Kidney Diseases, Jinling Hospital, Nanjing Medical University, Nanjing, China.
Center for Kidney Disease, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
J Clin Pathol. 2025 Jul 18;78(8):562-568. doi: 10.1136/jcp-2024-209620.
Light chain proximal tubulopathy (LCPT) is a rare complication of paraprotein-related diseases. We report a case series to present the clinicopathological characteristics and outcomes of LCPT.
A multicentre retrospective case series of 47 patients with LCPT, consisting of 36 crystalline, three non-crystalline, and eight mixed LCPTs, was studied between January 2007 and December 2023.
The median age at diagnosis was 57 years. Presentations included proteinuria (100%), renal insufficiency (62%) and Fanconi syndrome (68%). The underlying haematological diagnoses were monoclonal gammopathy of renal significance in 81% and multiple myeloma in 19%. Monoclonal light chain (LC) was detected in all cases using serum/urine-free LC assays or immunofixation electrophoresis. Among 36 crystalline LCPTs, 34 were κ-restricted and 2 λ-restricted. Three non-crystalline LCPTs were all λ-restricted. In mixed LCPTs, seven were κ-restricted and one was λ-restricted. Notably, 66% frozen-section immunofluorescence failed to reveal restricted LC, requiring paraffin-immunofluorescence or immunoelectron microscopy. The appearance of inclusions displayed intraindividual homogeneity but interindividual heterogeneity in 42 patients and notable intraindividual heterogeneity in the remaining 5 patients. Haematological complete response, very good partial response and partial response occurred in 61%. Kidney function improved or remained stable in 84%, worsened in 8% and progressed to end-stage renal disease in 8%.
Proteinuria and kidney dysfunction are the most common but less-specific renal manifestations of LCPTs, with most featuring Fanconi syndrome. Crystalline LCPT, primarily associated with κ-LC, is the predominant form. Most inclusions displayed intraindividual homogeneity and interindividual heterogeneity by electron microscopy. Most achieved haematological responses and favourable renal outcomes.
轻链近端肾小管病（LCPT）是副蛋白相关疾病的一种罕见并发症。我们报告一组病例，以呈现LCPT的临床病理特征及转归。
对2007年1月至2023年12月期间的47例LCPT患者进行了一项多中心回顾性病例系列研究，其中包括36例结晶性、3例非结晶性和8例混合性LCPT。
诊断时的中位年龄为57岁。临床表现包括蛋白尿（100%）、肾功能不全（62%）和范科尼综合征（68%）。潜在的血液学诊断为具有肾脏意义的单克隆丙种球蛋白病的占81%，多发性骨髓瘤的占19%。所有病例均通过血清/尿游离轻链检测或免疫固定电泳检测到单克隆轻链（LC）。在36例结晶性LCPT中，34例为κ限制型，2例为λ限制型。3例非结晶性LCPT均为λ限制型。在混合性LCPT中，7例为κ限制型，1例为λ限制型。值得注意的是，66%的冰冻切片免疫荧光未能显示限制性LC，需要石蜡免疫荧光或免疫电子显微镜检查。42例患者的包涵体外观显示个体内均一性但个体间异质性，其余5例患者显示明显的个体内异质性。血液学完全缓解、非常好的部分缓解和部分缓解发生率为61%。84%的患者肾功能改善或保持稳定，8%的患者肾功能恶化，8%的患者进展为终末期肾病。
蛋白尿和肾功能不全是LCPT最常见但特异性较低的肾脏表现，大多数伴有范科尼综合征。结晶性LCPT主要与κ-LC相关，是主要形式。多数包涵体通过电子显微镜显示个体内均一性和个体间异质性。多数患者获得血液学缓解和良好的肾脏转归。
