血清游离轻链在鉴别诊断不同病因肾病的应用价值及其与患者肾功能分期的相关性分析

doi:10.16150/j.1671-2870.2023.02.010

摘要/Abstract

摘要：

目的：探讨血清游离轻链（serum free light chain，sFLC）对单克隆免疫球蛋白相关肾病的辅助诊断效能，及其与不同病因肾损伤患者肾功能分期间的相关性。方法：收集2017年1月至2021年9月上海交通大学医学院附属瑞金医院收治的非单克隆免疫球蛋白相关肾损伤患者368例、单克隆免疫球蛋白相关肾病患者64例和正常对照30例。检测各组sFLC，并使用GraphPad Prism v9.0软件进行统计学分析。结果：单克隆免疫球蛋白相关肾病患者的sFLC水平显著高于非单克隆免疫球蛋白相关肾损伤患者（sFLCκ，453.0 mg/L比53.2 mg/L; sFLCλ，382.5 mg/L比56.5 mg/L），且sFLCκ/λ比值异常。当sFLCκ/λ比值阈值设为1.925时，其诊断κ型单克隆免疫球蛋白病的灵敏度为84.4%，特异度为97.0%，受试者操作特征曲线的曲线下面积（area under the curve, AUC）为0.933 9。当sFLCκ/λ比值阈值设为0.455时，其诊断λ型单克隆免疫球蛋白病的灵敏度为84.4%，特异度为87.2%，AUC为0.915 9。sFLC水平与非单克隆免疫球蛋白相关肾病患者肾功能分期间的相关性（r=0.7）优于单克隆免疫球蛋白相关肾病患者（r=0.4），且sFLC水平与患者肾功能分期间的相关性较sFLCκ/λ比值（r<0.3）更高。结论：sFLCκ/λ比值可用于单克隆免疫球蛋白相关肾病与非单克隆免疫球蛋白相关肾损伤的鉴别诊断，而sFLC水平较sFLCκ/λ比值更适于患者的肾功能评估。

关键词: 血清游离轻链, 单克隆免疫球蛋白病, 肾功能, 鉴别诊断, 相关性

Abstract:

Objective: To assess the diagnostic efficacy of serum free light chain (sFLC) levels in differential diagnosis of monoclonal gammopathies of renal significance, and to evaluate the correlation between sFLC and stages of kidney disease caused by various etiologies. Methods: Three hundred and sixty-eight patients with non-monoclonal gammopathy-related nephropathy, 64 patients with monoclonal gammopathy of renal significance, and 30 normal individuals were enrolled from Shanghai Ruijin Hospital from January 2017 to September 2021. The sFLC levels were measured by IMMAGE 800 Protein Chemistry Analyzer (Beckman, USA). The statistical analysis was carried out by GraphPad Prism v9.0. Results: The sFLC levels in patients with monoclonal gammopathy were significantly higher than that in patients with non-monoclonal gammopathy (sFLCκ：453.0 mg/L vs. 53.2 mg/L; sFLCλ：382.5mg/L vs. 56.5mg/L, respectively), and the sFLCκ/λ ratio was abnormal. The best predictive value for diagnosing monoclonal gammopathy with kappa light-chain isotype was achieved using a cut-off value of sFLCκ/λ ratio at 1.952 (AUC 0.933 9; sensitivity 84.4%; specificity 97.0%). The best predictive value for diagnosing monoclonal gammopathy with lambda light-chain isotype was achieved using a cut-off value of sFLCκ/λ ratio at 0.455 (AUC 0.915 9; sensitivity 84.4%; specificity 87.2%). The correlation between sFLC levels and stages of kidney disease （r=0.7） was stronger in patients with non-monoclonal gammopathy compared with those with monoclonal gammopathy （r=0.4）. The correlation coefficients between sFLC levels and kidney disease stages are higher than those of the sFLCκ/λ ratio （r<0.3）. Conclusions: The sFLCκ/λ ratio could be used for differential diagnosis of monoclonal gammopathy of renal significance, whereas sFLC levels are more suitable for the evaluation of renal function in patients compared with sFLCκ/λ ratio.

Key words: Serum free light chain, Monoclonal gammopathies, Renal function, Differential diagnosis, Correlation

中图分类号:

R692

谢雅琼, 林孝怡. 血清游离轻链在鉴别诊断不同病因肾病的应用价值及其与患者肾功能分期的相关性分析[J]. 诊断学理论与实践, 2023, 22(02): 166-171.

XIE Yaqiong, LIN Xiaoyi. Value of serum-free light chain assay in differential diagnosis and staging of nephropathy of various etiologies[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(02): 166-171.

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Group	n	sFLCκ（mg/L）	sFLCλ（mg/L）	sFLCκ/λ	Urea(mmol/L)	Creatinine(μmol/L)	Uric acid(μmol/L)
Normal range		3.3-19.4	5.7-26.3	0.26-1.65	2.5-7.1	53.0-97.0	160-430
Normal control	30	10.6±4.7	11.1±4.6	1.12±0.63	3.9±1.3	69.3±12.5	268.7±88.5
Cardiovascular disease	47	63.4±71.3^*	60.7±54.1^*	1.06±0.94	13.8±9.2	294.1±273.5	435.3±96.4
Diabetes	38	68.6±51.9^*	74.2±51.0^*	1.13±1.19	15.1±7.7	302.1±265.2	390.1±100.7
Primary glomerulonephritis	56	62.3±100.2^*	56.8±48.3^*	0.89±0.57	12.8±10.1	257.1±309.6	373.4±141.2
Autoimmune disease	121	54.6±86.4^*	55.0±52.6^*	0.83±0.45	8.8±7.5	146.8±169.5	385.3±117.1
IgA nephropathy	106	36.6±53.8^*	49.9±67.7^*	0.72±0.33^#	8.8±6.0	163.3±181.4	376.9±89.8
Monoclonal gammopathy with κ isotype	32	453.0±1275.0^*	28.6±23.3^*	22.6±41.7^*	14.3±10.8	264.9±215.0	413.3±184.4
Monoclonal gammopathy with λ isotype	32	21.9±15.6^*	382.5±728.3^*	0.3±0.2^#	10.7±8.3	214.7±234.2	358.2±133.2

Disease	Parameter	Cut-off value	Sensitivity（%）	Specificity（%）	AUC
Monoclonal gammopathy with κ isotype	sFLCκ	>176.5 mg/L	62.5	92.1	0.832 6
Monoclonal gammopathy with κ isotype	sFLCκ/λ	>1.925	84.4	97.0	0.933 9
Monoclonal gammopathy with λ isotype	sFLCλ	>82.3 mg/L	68.8	79.1	0.797 6
Monoclonal gammopathy with λ isotype	sFLCκ/λ	<0.455	84.4	87.2	0.915 9

Groups		sFLCκ	sFLCλ	sFLCκ/λ
Non-monoclonal gammopathy	r	0.688 7	0.661 2	0.300 0
	P	<0.000 1	<0.000 1	<0.000 1
Cardiovascular disease	r	0.835 5	0.894 2	/
	P	<0.000 1	<0.000 1	ns
Diabetes	r	0.767 2	0.727 1	/
	P	<0.000 1	<0.000 1	ns
Primary glomerulonephritis	r	0.772 8	0.721 7	0.501 0
	P	<0.000 1	<0.000 1	<0.000 1
Autoimmune disease	r	0.516 8	0.537 9	/
	P	<0.000 1	<0.000 1	ns
IgA nephropathy	r	0.689 8	0.687 5	0.211 0
	P	<0.000 1	<0.000 1	0.029 9
	P	0.003 9	0.006 8	ns
Monoclonal gammopathy with	r	/	0.524 4	/
κ isotype	P	ns	0.002 1	ns
Monoclonal gammopathy with	r	0.478 0	0.610 1	-0.371 9
λ isotype	P	0.005 7	0.000 2	0.036 1