轻链型淀粉样变性肾损伤的临床特征及诊治情况分析

Kidney injury caused by light chain amyloidosis:clinical features and treatment status

目的探讨轻链型淀粉样变性(AL)肾损伤的临床特征,分析其诊治及预后情况,为临床诊治提供参考。方法回顾性分析2014年1月-2021年10月收治于上海交通大学医学院附属瑞金医院北部院区肾脏内科的34例轻链型AL及同期住院的11例非AL单克隆免疫球蛋白病(MGRS)肾损伤患者的临床资料,分别纳入轻链型AL组和非AL MGRS组。收集患者的一般人口学资料、基础疾病情况、器官受累情况、24 h尿蛋白定量、血肌酐、血尿酸、EPI公式估算的肾小球滤过率(EPI-eGFR)、血白蛋白、补体,以及M蛋白相关检查等。并对患者的肾脏疾病进行分期和评价疗效。结果纳入患者的初诊年龄为(58.3±8.4)岁,不同性别患者初诊年龄的差异无统计学意义(t=1.121,P=0.271)。患者初诊时单纯肾脏受累比例为64.7%(22/34),伴心脏受累比例为29.4%(10/34),伴消化道受累比例为5.9%(2/34)。不同性别初诊时肾脏预后分期的差异无统计学意义(χ^(2)=1.638,P=0.201)。轻链型AL组的血肌酐水平、血白蛋白水平、尿红细胞≥5/高倍镜视野(HP)患者比例、高血压患者比例均显著低于非AL MGRS组(Z=-3.645、-3.769,P值均<0.01;χ^(2)=6.433、8.779,P=0.011、0.003),而EPI-eGFR、24 h尿蛋白定量、血红蛋白水平、肾病综合征患者比例均显著高于非AL MGRS组(Z=-3.646、2.037、-2.841,P<0.01;χ^(2)=10.175,P=0.001)。轻链型AL患者血清免疫固定电泳(IFE)阳性率为70.6%,尿IFE阳性率为82.4%,血或尿IFE至少1项阳性的患者比例为88.2%;血清IFE类型以IgG-λ最常见(32.35%),其次为IgA-λ(17.65%),尿IFE类型以λ型最常见(76.47%)。血清游离轻链(FLC)比值异常率(>1.65或<0.26)为68.8%,如采用肾脏病FLC比值参考范围(>3.10或<0.37)则血清FLC比值异常率为81.3%。轻链型AL组患者中AL-λ型比例为88.2%(30/34),AL-κ型比例为11.8%(4/34)。AL-κ型患者的初诊年龄为(68.0±7.4)岁,显著高于AL-λ型的(57.0±7.7)岁(P=0.012)。AL-κ型相较AL-λ型患者更常见消化道受累(50%比0,P=0.011)。38.2%(13/34)的轻链型AL组患者未接受蛋白酶体抑制剂为主的初始化学治疗(简称化疗)方案,其中,4例放弃化疗仅行对症支持治疗,4例予VAD(长春新碱+阿糖胞苷+地塞米松)方案治疗,4例予免疫调节剂方案(沙利度胺)治疗,1例予糖皮质激素+环磷酰胺方案治疗。初始治疗方案为蛋白酶体抑制剂的患者共21例,其中,确诊后立即接受治疗的仅57.1%(12/21)。本研究中位随访时间13.5(1.0~88.0)个月。在接受化疗的30例患者中,有14例达到完全缓解(CR),血液学总缓解率为57%,中位缓解时间6(1~8)个月。有25例进行了肾脏疗效评估,肾脏总缓解率为56%,中位缓解时间8(1~23)个月,CR率、非常好的部分缓解(VGPR)率、部分缓解(PR)率分别为12%、20%、24%。结论联合血清、尿IFE和血清FLC比值检测有助于筛查轻链型AL。轻链型AL的临床特征表现为M蛋白血症合并肾病综合征、受累器官≥2个、血压正常、镜下血尿不明显。

Objective To analyze clinical features and treatment status of kidney injury caused by light chain amyloidosis(AL),so as to provide evidence for diagnosis and treatment of the disease.Methods Clinical data of 34 patients with light chain AL and 11 patients with renal lesions of non-AL MGRS(monoclonal gammopathy with renal significance)hospitalized at renal department of Ruijin Hospital North District from January 2014 to October 2021 were enrolled in this retrospective study.The demographic information,basic diseases,organ involvement,24-hour urinary protein,serum creatinine,serum uric acid,estimated glomerular filtration rate by CKD-EPI formula(EPI-eGFR),serum albumin,complement and M protein were collected.The staging and curative effect of renal disease were evaluated.Results The average age of the patients at diagnosis was(58.3±8.4)years.There was no significant difference in the age at diagnosis between males and females(t=1.121,P=0.271).Only the kidney was involved in 64.7%(22/34)patients,29.4%(10/34)had heart involvement and 5.9%(2/34)had gastrointestinal involvement.There was no significant difference in renal prognostic stages between different genders(χ^(2)=1.638,P=0.201).Compared with the patients with non-AL MGRS,the patients with light chain AL had lower serum creatine(Z=-3.645,P<0.01),lower serum albumin(Z=-3.769,P<0.01),less hematuria(χ^(2)=6.433,P=0.011),less hypertension(χ^(2)=8.779,P=0.003),higher EPI-eGFR(Z=-3.646,P<0.01),higher 24-hour urinary protein(Z=2.037,P<0.01),higher hemoglobin(Z=-2.841,P<0.01)and more nephrotic syndrome(χ^(2)=10.175,P=0.001).Serum and urine immunofixation electrophoresis(IFE)results were positive in 70.6%and 82.4%of patients with light chain AL,respectively,and 88.2%of the patients had at least one positive IFE result(serum or urine).IgG-λwas the most common serum IFE type(32.35%),followed by IgA-λ(17.65%).Typeλwas the most common urinary IFE type(76.47%).The abnormal rate of serum FLC ratio was 68.8%(>1.65 or<0.26).When abnormal serum FLC ratio(renal reference range:>3.10 or<0.37)was added as an indicator for the presence of monoclonal protein,the positive rate was 81.3%.AL-λtype and AL-κtype accounted for 88.2%(30/34)and 11.8%(4/34)in patients with AL-renal amyloidosis,respectively.Patients of AL-κtype were older than patients of AL-λtype([68.0±7.4]years vs.[57.0±7.7]years,P=0.012).Gastrointestinal involvement was more common in patients of AL-κtype than AL-λtype(50%vs 0%,P=0.011).38.2%(13/34)of patients with light chain AL did not receive initial chemotherapy based on proteasome inhibitors.Of them,4 patients gave up chemotherapy and only received symptomatic and supportive treatment,4 patients were treated with VAD(vincristine+cytarabine+dexamethasone),4 patients were treated with thalidomide,and one was treated with glucocorticoid+cyclophosphamide.Proteasome inhibitor was taken as initial therapy in 21 patients,in whom 12 patients(57.1%)were treated immediately after diagnosis.The median follow-up time was 13.5(1.0-88.0)months.Of the 30 patients receiving hematological chemotherapy,14 achieved complete remission(CR),the total hematological remission rate was 57%,and the median remission time was 6(1-8)months.Renal efficacy was evaluated in 25 patients.The total renal remission rate was 56%,and the median remission time was 8(1-23)months.The rates of CR,very good partial remission(VGPR)and partial remission(PR)were 12%,20%and 24%,respectively.Conclusion A combination of IFE(serum and urine)and serum FLC ratio is helpful to screen light chain AL.light chain AL is characterized by monoclonal proteinemia complicated with nephrotic syndrome,more than 2 organs involvement,low blood pressure and obscure microscopic hematuria.