Defining new reference intervals for serum free light chains in individuals with chronic kidney disease: Results of the iStopMM study
Þórir Einarsson Long, Ólafur S. Indridason, Runólfur Pálsson, Sæmundur Rögnvaldsson, Þorvarður Jón Löve, Sigrún Þorsteinsdóttir, Ingigerður Sverrisdóttir, Brynjar Viðarsson, Páll T. Önundarson, Bjarni A. Agnarsson, Margrét Sigurðardóttir, Ingunn Þorsteinsdóttir, Ísleifur Ólafsson, Ásdís Rósa Þórðardóttir, Elías Eyþórsson, Ásbjörn Jónsson, Gauti Kjartan Gíslason, Andri Ólafsson, Hlíf Steingrímsdóttir, Malin Hultcrantz, Brian G.M. Durie, Stephen Harding, Ola Landgren, Sigurður Y. Kristinsson
Abstract
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.