TY - JOUR
T1 - Defining new reference intervals for serum free light chains in individuals with chronic kidney disease
T2 - Results of the iStopMM study
AU - Long, Thorir Einarsson
AU - Indridason, Olafur Skuli
AU - Palsson, Runolfur
AU - Rognvaldsson, Sæmundur
AU - Love, Thorvardur Jon
AU - Thorsteinsdottir, Sigrun
AU - Sverrisdottir, Ingigerdur Solveig
AU - Vidarsson, Brynjar
AU - Onundarson, Pall Torfi
AU - Agnarsson, Bjarni Agnar
AU - Sigurdardottir, Margret
AU - Thorsteinsdottir, Ingunn
AU - Olafsson, Isleifur
AU - Thordardottir, Asdis Rosa
AU - Eythorsson, Elias
AU - Jonsson, Asbjorn
AU - Gislason, Gauti
AU - Olafsson, Andri
AU - Steingrimsdottir, Hlif
AU - Hultcrantz, Malin
AU - Durie, Brian G M
AU - Harding, Stephen
AU - Landgren, Ola
AU - Kristinsson, Sigurdur Yngvi
N1 - © 2022. The Author(s).
PY - 2022/9/14
Y1 - 2022/9/14
N2 - 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 m2, 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 m2 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.
AB - 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 m2, 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 m2 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.
KW - Humans
KW - Immunoglobulin Light Chains
KW - Immunoglobulin lambda-Chains
KW - Prospective Studies
KW - Reference Values
KW - Renal Insufficiency, Chronic/diagnosis
UR - http://www.scopus.com/inward/record.url?scp=85137808095&partnerID=8YFLogxK
U2 - 10.1038/s41408-022-00732-3
DO - 10.1038/s41408-022-00732-3
M3 - Journal article
C2 - 36100605
VL - 12
SP - 1
EP - 8
JO - Blood Cancer Journal
JF - Blood Cancer Journal
SN - 2044-5385
IS - 9
M1 - 133
ER -