Abstract
BackgroundMonoclonal serum free light chains (sFLC) are a well-known cause of renal impairment (RI) in patients with multiple myeloma (MM). As an indicator of monoclonality, sFLC ratio has acquired a key role in the diagnosis and monitorization of the disease. However, its interpretation is altered in patients with chronic kidney disease (CKD). This study aims to evaluate the modification of the sFLC ratio reference range in patients with CKD, and propose an optimal range for patients with CKD.MethodsSerum FLC κ/λ ratio and estimated glomerular filtration rate (eGFR) were retrospectively analyzed in 113 control patients (without hematologic disease), 63 patients with MM in complete remission and 347 patients with active MM. The three groups included patients with CKD (eGFR < 90).ResultsIn the group of patients without active MM (n = 176), the sFLC ratio increased at different stages of CKD without pathological significance, with an increase in the number of false positives specially when eGFR is ≤55 ml/min. An optimal range was established for patients with eGFR ≤55 ml/min/1.73 m2: 0.82–3,6 with maximum sensitivity + specificity for that group with an improvement in the Area under the curve (AUC), 0.91 (0.84–0.97) compared with the current ranges proposed by Katzmann and Hutchinson.ConclusionsThis study confirms the influence of eGFR on the interpretation of the sFLC ratio, showing a decreasing specificity in progressive CKD stages when using the reference sFLC range (Katzmann), especially in patients with eFGR ≤55. According to our results, we suggest a modified optimal range (0.82–3,6) for eGFR ≤55 ml/min/1.73 m2. It is necessary to validate this modified range in larger and prospective studies.
Highlights
Monoclonal serum free light chains are a well-known cause of renal impairment (RI) in patients with multiple myeloma (MM)
Patients and study design The κ/λ free light chains (FLC) ratio in serum and estimated glomerular filtration rate (eGFR) was analyzed retrospectively by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) in 1469 consecutive patients attended in Hospital Clínic of Barcelona between December 2014 and December 2017
The sensitivity and specificity of the serum free light chains (sFLC) ratio normal range reported in the literature (0.26–1.65 and 0.37–3.1) [7, 8] was measured in the cohort; second, Receiver Operating Characteristic (ROC) analysis was carried out dividing the population of each of the 2 cohorts in subgroups of different eGFR, establishing the optimal cut-off for the k/λ sFLC ratio and for the eGFR
Summary
Monoclonal serum free light chains (sFLC) are a well-known cause of renal impairment (RI) in patients with multiple myeloma (MM). As an indicator of monoclonality, sFLC ratio has acquired a key role in the diagnosis and monitorization of the disease. Its interpretation is altered in patients with chronic kidney disease (CKD). In MM, renal disease is the most characteristic and extensively studied organ involvement, being cast nephropathy the most frequent injury pattern as well as the predominant cause of renal impairment (RI), i.e. chronic kidney disease (glomerular filtration rate < 60 ml/min/1.73 m2), secondary to acute kidney injury (AKI) [4]. The development of an effective nephelometric assay to quantify the sFLC concentration has optimized the screening and monitoring algorithms of MM [6], using an abnormal κ/λ ratio as an indicator of clonality. There is evidence that renal function influences the interpretation of this ratio
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