A comparative study on the value of urine free light chain and urine total light chain assays in quantitative monitoring of urine light chain

Abstract

Abstract:

Objective:To explore whether the novel urine free light chain (uFLC) assay is superior to the traditional urine total light chain (uTLC) assay in quantitative monitoring of urine light chain.Methods:A total of 458 paired samples of blood and were collected from 280 patients (including 153 patients with plasma cell diseases and 137 patients with non-plasma cell diseases) from January 2022 to March 2023 at Ruijin Hospital， Shanghai Jiao Tong University School of Medicine. The positive concordance rates and correlations between the κ value, λ value and κ/λ ratio of uFLC and uTLC assays with the results of urinary immunofixation electrophoresis (uIFE) and serum free light chain (sFLC) were analyzed by Chi-squared test,MeNemar’stest andSpearmancorrelation coefficient calculation.Result:Among the 102 uIFE positive samples, 88.2% (90/102) of the samples had abnormal uFLC κ/λ ratio, and 87.3% (89/102) had abnormal uTLC κ/λ ratio (P<0.001). Among the 183 samples with abnormal sFLC κ/λ ratio, 65.6% (120/183) of the samples had abnormal uFLC κ/λ ratio, and 51.4% (94/183) had abnormal uTLC κ/λ ratio (P<0.001). Among the 457 samples with both uFLC and uTLC results, 164 samples (35.9%) had abnormal uFLC κ/λ ratio, and 123 samples (26.9%) had abnormal uTLC κ/λ ratio (P<0.001). There was a strong correlation between the levels of κ light chain, λ light chain, and κ/λ ratio of uFLC and uTLC (rvalues were 0.849, 0.697 and 0.648, respectively,P<0.001). Thervalues between the levels of corresponding κ light chain, λ light chain, and κ/λ ratio of uFLC and sFLC were 0.628, 0.552, and 0.640 (P<0.001), while the r values between the levels of κ light chain, λ light chain, and κ/λ ratio of uTLC assay and sFLC assay were 0.520, 0.533, and 0.551, respectively (P<0.001). Moderate correlations were indicated and the correlation between uFLC and sFLC was stronger than that between uTLC and sFLC.Conclusions:Compared with the uTLC assay, the uFLC assay is more sensitive in the quantitative monitoring of urine light chain and has higher positive concordance rates and stronger correlations with uIFE and sFLC results, indicating an objective quantitative determination of urine light chain. It is recommended to prioritize the use of uFLC assay in clinical quantitative monitoring of urinary light chain.

Key words:Monoclonal protein,Urine free light chain,Urine total light chain,Concordance rate

CLC Number:

R446.122

LIU Yuanfang, WANG Yan, SHI Xinming, XU Wenbin, WANG Xuefeng, MI Jianqing. A comparative study on the value of urine free light chain and urine total light chain assays in quantitative monitoring of urine light chain[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(02): 172-177.

Figures/Tables4

Indice	uIFE
uFLC κ/λ				<0.001
Abnormal	162 (35.8%)	90 (88.2%)	72 (20.5%)
Normal	291 (64.2%)	12 (11.8%)	279 (79.5%)
Total	453 (100%)	102 (100%)	351(100%)
uTLC κ/λ				<0.001
Abnormal	123 (27.1%)	89 (87.3%)	34 (9.7%)
Normal	331 (72.9%)	13 (12.7%)	318 (90.3%)
Total	454 (100%)	102 (100%)	352(100%)

Table 1

Indice	sFLC κ/λ
uFLC κ/λ				<0.001
Abnormal	163 (36.3%)	120 (65.6%)	43 (16.2%)
Normal	286 (63.7%)	63 (34.4%)	223 (83.8%)
Total	449 (100%)	183 (100%)	266 (100%)
uTLC κ/λ				<0.001
Abnormal	123 (27.3%)	94 (51.4%)	29 (10.9%)
Normal	327 (72.7%)	89 (48.6%)	238 (89.1%)
Total	450 (100%)	183 (100%)	267 (100%)

Table 2

Indice	uFLC κ/λ
uTLC κ/λ				<0.001
Abnormal	123 (26.9%)	94 (20.6%)	29 (6.3%)
Normal	334 (73.1%)	70 (15.3%)	264 (57.8%)
Total	457 (100%)	164 (35.9%)	293 (64.1%)

Table 3

Indice	uTLC κ	uTLC λ	uTLC κ/λ	sFLC κ	sFLC λ	sFLC κ/λ
uFLC κ	0.849^*	-	-	0.628^*	-	-
uFLC λ	-	0.697^*	-	-	0.552^*	-
uFLC κ/λ	-	-	0.648^*	-	-	0.640^*
uTLC κ	-	-	-	0.520^*	-	-
uTLC λ	-	-	-	-	0.533^*	-
uTLC κ/λ	-	-	-	-	-	0.551^*

Table 4

References21

[1]	GUDOWSKA-SAWCZUK M, MROCZKO B. Free light chains as a novel diagnostic biomarker of immune system abnormalities in multiple sclerosis and HIV infection[J]. Biomed Res Int, 2019, 2019:8382132.
[2]	SINGH G. Concentrations of serum free light chains in kappa and lambda lesions in light-chain myelomas[J]. Lab Med, 2019, 50(2):189-193. doi:10.1093/labmed/lmy067pmid:30423164
[3]	RAJKUMAR S V. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management[J]. Am J Hematol, 2016, 91(7):719-734. doi:10.1002/ajh.24402pmid:27291302
[4]	NAKANO T, MATSUI M, INOUE I, et al. Free immunoglobulin light chain: its biology and implications in di-seases[J]. Clin Chim Acta, 2011, 412(11-12):843-849. doi:10.1016/j.cca.2011.03.007 URL
[5]	DIMOPOULOS M A, MOREAU P, TERPOS E, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2021, 32(3):309-322. doi:10.1016/j.annonc.2020.11.014pmid:33549387
[6]	RAJKUMAR S V, DIMOPOULOS M A, PALUMBO A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma[J]. Lancet Oncol, 2014, 15(12):e538-e548. doi:10.1016/S1470-2045(14)70442-5 URL
[7]	KYLE R A, DURIE B G, RAJKUMAR S V, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management[J]. Leukemia, 2010, 24(6):1121-1127. doi:10.1038/leu.2010.60pmid:20410922
[8]	KUMAR S, PAIVA B, ANDERSON K C, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma[J]. Lancet Oncol, 2016, 17(8):e328-e346. doi:10.1016/S1470-2045(16)30206-6pmid:27511158
[9]	史德宝, 卢敏, 潘亚萍, 等. 轻链检测在慢性肾脏病中的应用评估[J]. 安徽医科大学学报, 2022, 57(6):997-1001.
	SHI D B, LU M, PAN Y P, et al. Evaluation of the clinical application of light chain detection in chronic kidney disease[J]. Acta Univ Med Anhui, 2022, 57(6):997-1001.
[10]	PIERI M, PIGNALOSA S, FRANCESCHINI L, et al. Nephelometric assay of urine free light chains: an alternative and early clinical test for Bence-Jones protein quantification[J]. Clin Chem Lab Med, 2018, 56(12):e313-e315. doi:10.1515/cclm-2018-0402 URL
[11]	BASILE U, GULLI F, GRAGNANI L, et al. Free light chains: eclectic multipurpose biomarker[J]. J Immunol Methods, 2017, 451:11-19. doi:S0022-1759(17)30154-0pmid:28931470
[12]	王吉耀, 葛均波, 邹和建. 实用内科学[M]. 16版. 北京: 人民卫生出版社, 2022.
	WANG J Y, GE J B, ZOU H J. Practice of internal medicine[M]. 16th Ed.Beijing: People's Health Publishing House, 2022.
[13]	CHO J, LEE D H, YOO G, et al. Comparison of serum and urine free light chain analysis in clinical diagnosis[J]. Blood Res, 2022, 57(4):284-289. doi:10.5045/br.2022.2022187pmid:36419240
[14]	BHOLE M V, SADLER R, RAMASAMY K. Serum-free light-chain assay: clinical utility and limitations[J]. Ann Clin Biochem, 2014, 51(Pt 5):528-542. doi:10.1177/0004563213518758pmid:24489083
[15]	DISPENZIERI A, ZHANG L, KATZMANN J A, et al. Appraisal of immunoglobulin free light chain as a marker of response[J]. Blood, 2008, 111(10):4908-4915. doi:10.1182/blood-2008-02-138602pmid:18364469
[16]	NIEWMIERZYCKA A, KURMAN M, LEŚNIAK M, et al. Prevalence and clinical significance of abnormal serum kappa/lambda light chain ratio in patients with chronic kidney disease[J]. Pol Arch Med Wewn, 2015, 125(7-8):532-537.
[17]	XU L, ZHAO B, SUN Y, et al. Using two detection methods to observe the changes and significance of free light chain in serum and urine in patients with renal insufficiency[J]. Biomed Res Int, 2022, 2022:5536199.
[18]	DELGADO J C. Value of urinary free light chain testing for monitoring of bence jones proteinuria[J]. J Appl Lab Med, 2019, 3(6):1059-1060. doi:10.1373/jalm.2018.027862pmid:31639698
[19]	XU Z L, WU C, TENG W H, et al. Exploring the relationship between serum and urinary free light chain levels during the different phases of renal damage in multiple myeloma patients[J]. Indian J Hematol Blood Transfus, 2015, 31(3):352-355. doi:10.1007/s12288-014-0480-3 URL
[20]	廖丹, 刘霞, 李辉军, 等. 多发性骨髓瘤血、尿总轻链与游离轻链相符率比较及其临床意义[J]. 临床内科杂志, 2016, 33(4):243-245.
	LIAO D, LIU X, LI H J, et al. The comparison of accordant rate of total light chains and free light chains in serum and urine and its clinical significance of muitiple myeloma[J]. J Clin Intern Med, 2016, 33(4):243-245.
[21]	DEJOIE T, CORRE J, CAILLON H, et al. Responses in multiple myeloma should be assigned according to serum, not urine, free light chain measurements[J]. Leukemia, 2019, 33(2):313-318. doi:10.1038/s41375-018-0339-ypmid:30573778