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Defining new reference intervals for serum free light chains in individuals with chronic kidney disease : Results of the iStopMM study

Defining new reference intervals for serum free light chains in individuals with chronic kidney disease : Results of the iStopMM study


Title: Defining new reference intervals for serum free light chains in individuals with chronic kidney disease : Results of the iStopMM study
Author: Long, Þórir Einarsson
Indridason, Ólafur Skúli
Pálsson, Runólfur
Rögnvaldsson, Sæmundur
Löve, Þorvarður Jón   orcid.org/0000-0002-2680-6120
Thorsteinsdóttir, Sigrún
Sverrisdottir, Ingigerdur
Viðarsson, Brynjar
Önundarson, Páll Torfi
Agnarsson, Bjarni Agnar
... 14 more authors Show all authors
Date: 2022-09-14
Language: English
Scope: 1
University/Institute: University of Iceland
Landspitali - The National University Hospital of Iceland
Department: Internal Medicine and Emergency Services
Other departments
Faculty of Medicine
Clinical Laboratory Services, Diagnostics and Blood Bank
Office of Division of Clinical Services II
Cancer Center
Series: Blood Cancer Journal; 12(9)
ISSN: 2044-5385
DOI: https://doi.org/10.1038/s41408-022-00732-3
Subject: Lífefna- og sameindalíffræði; Blóðlæknisfræði; Myndgreining (læknisfræði); Nýrnalæknisfræði; Meinafræði; Gigtarlæknisfræði; Humans; Immunoglobulin Light Chains; Immunoglobulin lambda-Chains; Prospective Studies; Reference Values; Renal Insufficiency, Chronic/diagnosis; Hematology; Oncology
URI: https://hdl.handle.net/20.500.11815/3484

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Citation:

Long , Þ E , Indridason , Ó S , Pálsson , R , Rögnvaldsson , S , Löve , Þ J , Thorsteinsdóttir , S , Sverrisdottir , I , Viðarsson , B , Önundarson , P T , Agnarsson , B A , Sigurðardóttir , M , Þorsteinsdóttir , I , Ólafsson , Í , Thordardottir , A R , Eyþórsson , E S , Jónsson , Á , Gíslason , G K , Ólafsson , A , Steingrímsdóttir , H , Hultcrantz , M , Durie , B G M , Harding , S , Landgren , O & Kristinsson , S Y 2022 , ' Defining new reference intervals for serum free light chains in individuals with chronic kidney disease : Results of the iStopMM study ' , Blood Cancer Journal , vol. 12 , no. 9 , 133 , pp. 133 . https://doi.org/10.1038/s41408-022-00732-3

Abstract:

Serum free light chain (FLC) concentration is greatly affected by kidney function. Using a large prospective population-based cohort, we aimed to establish a reference interval for FLCs in persons with chronic kidney disease (CKD). A total of 75422 participants of the iStopMM study were screened with serum FLC, serum protein electrophoresis and immunofixation. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. Central 99% reference intervals were determined, and 95% confidence intervals calculated. Included were 6461 (12%) participants with measured FLCs, eGFR < 60 mL/min/1.73 m 2, not receiving renal replacement therapy, and without evidence of monoclonality. Using current reference intervals, 60% and 21% had kappa and lambda FLC values outside the normal range. The FLC ratio was outside standard reference interval (0.26-1.65) in 9% of participants and outside current kidney reference interval (0.37-3.10) in 0.7%. New reference intervals for FLC and FLC ratio were established. New reference intervals for the FLC ratio were 0.46-2.62, 0.48-3.38, and 0.54-3.30 for eGFR 45-59, 30-44, and < 30 mL/min/1.73 m 2 groups, respectively. The crude prevalence of LC-MGUS in CKD patients was 0.5%. We conclude that current reference intervals for FLC and FLC ratio are inaccurate in CKD patients and propose new eGFR based reference intervals to be implemented.

Description:

Funding Information: Dr. Landgren has received grant support from: NCI/NIH, FDA, LLS, Rising Tide Foundation, Memorial Sloan Kettering Cancer Center, MMRF, IMF, Paula, and Rodger Riney Foundation, Perelman Family Foundation, Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, Karyopharm; has received honoraria for scientific talks/participated in advisory boards for: Adaptive, Amgen, Binding Site, BMS, Celgene, Cellectis, Glenmark, Janssen, Juno, Pfizer; and served on Independent Data Monitoring Committees (IDMC) for international randomized trials by: Takeda, Merck, Janssen, Theradex. Dr. Hultcrantz has recevied grant support from GSK, Amgen, Daiichi Sankyo, Cosette Pharmaceuticals, and has received honoraria for scientific talks/participated in advisory boards for BMS, Curio Science, and Intellisphere LLC. All other authors declare no potential conflicts of interest. Funding Information: Dr. Kristinsson has received research funding from International Myeloma Foundation, European Research Council, Icelandic Center for Research (Rannís), Amgen, Celgene. Dr. Long has received research funding from the Icelandic Center for Research (Rannís). Dr. Landgren thanks Sylvester Comprehensive Cancer Center Core Grant (P30 CA240139) and Paula and Rodger Riney Foundation for support of his research. Dr. Hultcrantz thanks the Memorial Sloan Kettering Cancer Center Core Grant (P30 CA008748). The iStopMM study is funded by the Black Swan Research Initiative by the International Myeloma Foundation, the European Research Council, and the Icelandic Center for Research. Screening tests for the iStopMM study are performed by The Binding Site Ltd. Birmingham, UK. Additional funding is provided by the University of Iceland, Landspitali–The National University Hospital, and the Icelandic Cancer Society. Funding Information: Dr. Kristinsson has received research funding from International Myeloma Foundation, European Research Council, Icelandic Center for Research (Rannís), Amgen, Celgene. Dr. Long has received research funding from the Icelandic Center for Research (Rannís). Dr. Landgren thanks Sylvester Comprehensive Cancer Center Core Grant (P30 CA240139) and Paula and Rodger Riney Foundation for support of his research. Dr. Hultcrantz thanks the Memorial Sloan Kettering Cancer Center Core Grant (P30 CA008748). The iStopMM study is funded by the Black Swan Research Initiative by the International Myeloma Foundation, the European Research Council, and the Icelandic Center for Research. Screening tests for the iStopMM study are performed by The Binding Site Ltd. Birmingham, UK. Additional funding is provided by the University of Iceland, Landspitali–The National University Hospital, and the Icelandic Cancer Society. Publisher Copyright: © 2022, The Author(s).

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