The value of serum immunoglobulin free light chain assessment in patients with monoclonal gammopathies and acute renal failure.

"DISCUSSION: Recently, an assay for serum FLC became commercially available for use as a marker for diagnosing and screening monoclonal gammopathies [7,8,9,10]. There are 3 indications for using serum FLC to diagnose and screen MM and related diseases. First, screening serum using SPE and SIFE with FLC levels is highly sensitive and eliminates the necessity of using 24-h urine collection for the diagnosis of related diseases, except for light chain amyloidosis. Second, FLC assessment has prognostic importance for all plasma cell dyscrasias. Third, FLC assay provides insight into the screening of oligo-secretory plasma cell dyscrasias, quantitatively [9,12,13]. : Most kidney disease associated with monoclonal gammopathies is caused by monoclonal FLCs, which is a consequence of the kinetics of FLC clearance from the serum by the kidneys. As such, any structural and functional abnormalities in the kidneys and/or excess production of FLCs can lead to deposition and precipitation in situ [8]. The mechanisms involved in the nephrotoxicity of monoclonal FLCs are activation of inflammatory mediators in proximal tubules, proximal tubule necrosis, acquired Fanconi syndrome due to FLC deposition, cast nephropathy, light chain amyloidosis, and light chain deposition disease [14,15]. : There are limited data concerning the use FLC assays in patients that present with renal disease. In general, as renal clearance decreases, FLC κ and λ increase, but no change occurs in the FLC κ:λ ratio; however, different reference ranges must be evaluated in patients with renal disease in order to increase the specificity and sensitivity. Some patients with plasma cell dyscrasias may present with renal pathologies, and delayed identification and treatment leads to irreversible renal failure [8,10]. The present study aimed to evaluate the sensitivity and specificity of the FLC κ:λ ratio for detecting paraproteinemias in patients that presented with ARF. Paraproteinemias are more prevalent in older populations; therefore, we included patients aged >50 years, and because of elevated FLC levels in patients with diabetes, liver diseases, and collagen tissue diseases, such patients were excluded. : It has been reported that 24-h urine specimens can be obtained in 50% of patients [16,17]; however, in the present study urine specimens could not be evaluated because the patients presented with oligo and anuria. Studies have reported that cast nephropathy is the predominant cause of renal failure in patients with paraproteinemia that present with ARF [14,15]. In the present study, however, histologic types of ARF in the patients with and without MM could not be determined due to hemorrhagic diathesis and other medical conditions that contraindicated renal biopsy. Based on the published reference range for the FLC κ:λ ratio (0:26-1:65), it had a sensitivity of 71% and specificity of 96%, and a positive and negative predictive value of 62.9% and 97.3%, respectively, for the diagnosis of MM. In the present study there weren’t any significant differences in the sensitivity, specificity, or positive and negative predictive values between the FLC κ:λ ratio and SPE. : Hutchison et al. reported that based on the published reference range, the sensitivity of the FLC κ:λ ratio was 100% and its specificity was 93% [17]. The specificity of the FLC κ:λ ratio increased to 99% with no change in sensitivity when the renal reference range used was 0:37- 3:1. Moreover, based on the published reference range Katzmann et al. reported that the FLC κ:λ ratio has a sensitivity of 97%, specificity of 100%, and positive and negative predictive values of 100% and 99%, respectively [11]. The authors used nephelometric methods in these reports. Yet, Jaslowski et al. [18] reported that the FLC κ:λ ratio has lower sensitivity than SIFE (91.4% versus 72%) when turbidimetric methods are used, as in the present study. They examined 483 consecutive serum samples with abnormal SIFE findings and reported some of the samples had a normal FLC κ:λ ratio. As such, they suggest that in routine examination the FLC κ:λ ratio has lower diagnostic value. In the present study we also observed low specificity and sensitivity with turbidimetric methods; however, the present study population was small and this method was used firstly in our hospital. : FLC measurement is accepted as sufficiently sensitive for diagnosing non-secretory myeloma [19]; however, in the present study patients with MM confirmed via bone marrow biopsy findings that had normal SPE and SIFE findings also had a normal FLC κ:λ ratio (1:14). Despite the advantages of FLC assays, they do have some limitations, including reagent lot variability, low ratios due to high antigen levels, innumerable epitopes, and excess polymerization [20,21]. Elevated FLC κ and λ levels correlate strongly with declining kidney function [10]. To address the effect of renal function on FLC levels, patients assessed according to GFR as below and above to eGFR as 15 mL·min–1·1.73 m–2. κ levels had a statistical significance between two groups but λ and κ/λ values had no significance. : Based on Pearson’s correlation analysis in the present study, creatinine was positively correlated with FLC κ (P = 0.019, r = 0.27) and λ (P = 0.018, r = 0.272) levels, and eGFR was inversely correlated with FLC κ (P = 0.023, r = –0.262) and λ (P = 0.034, r = –0.246) levels. These results are consistent with other reports that emphasize the correlation between FLC levels and renal function [10]. The present study included only 82 patients and FLC levels were assessed using turbidimetric methods. The FLC κ:λ ratio had lower sensitivity and specificity than SPE and SIFE in the patients with MM that presented with ARF. In conclusion, additional, well-designed large-scale prospective studies are required to further delineate the diagnostic utility of the FLC κ:λ ratio. : Conflict of Interest Statement: The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/ or affiliations relevant to the subject matter or materials included."