Reference Ranges
Serum reference ranges
The most extensive serum free light chain normal range study has been conducted at Mayo Clinic, USA, using Binding Site Freelite assays for the BN™II1. In this study serum samples from 282 normal subjects aged from 21 to 90 years were assayed for free kappa and free lambda. The results from this trial are shown in the table below.
| Normal Adult Serum | Mean Concentration | Median Concentration | 95 Percentile Range |
|---|---|---|---|
| Free Kappa | 8.36 (mg/L) | 7.30 (mg/L) | 3.30-19.40 (mg/L) |
| Free Lambda | 13.43 (mg/L) | 12.40 (mg/L) | 5.71-26.30 (mg/L) |
| Mean | Median | Total Range | |
| Kappa/Lambda ratio | 0.63 | 0.60 | 0.26-1.65* |
* Borderline FLC ratios may be observed in renal impairment (including chronic kidney disease, CKD) or a polyclonal inflammatory response. In patients with renal impairment you may wish to use the published renal reference interval κ/λ ratio 0.37 - 3.1 (instead of 0.26 - 1.65).2
Kappa/Lambda ratio
The combination of individual concentrations of the free light chains and their ratio distinguishes a monoclonal increase from excess polyclonal production and renal dysfunction. The ratio of kappa to lambda in serum is the opposite of that seen in urine, with kappa being lower than lambda. This is despite the fact that there are approximately twice as many kappa producing plasma cells as lambda producing cells.
The explanation for this is kappa molecules (25kDa), that are normally present in serum as monomers, are filtered through the kidney at approximately three times the rate of the lambda molecules (50kDa) which are present as dimers. So although the production rate of lambda in normal patients is lower than kappa, the serum concentration of lambda is actually higher, due to slower renal clearance. This also explains why, in the urine, the reverse is seen with kappa being present at approximately twice the level of lambda.
The dot plot below shows the same normal range data as was used to generate the reference ranges. The kappa and lambda results for each person was plotted on a logarithmic scale. This form of data presentation inherently includes the kappa/lambda ratio and is a useful way of visualising results from different patient groups.
By means of a comparison, the same reference range data is plotted on the chart below along with the results of 224 patients identified as having Light Chain Multiple Myeloma. An additional 31 results are shown from patients suffering renal impairment from causes other than monoclonal gammopathies. This clearly shows the benefit of the κ/λ ratio as a sensitive marker of monoclonality as the ratio remains resolutely normal in the renal insufficiency patient group despite their increased levels of free light chains.
Serum κ and λ FLC concentrations in a selection of clinical conditions. Normal ranges for κ, λ (and κ/λ ratio - diagonal lines) are shown. Diagonal lines separate monoclonal from polyclonal FLC production. Sector numbers refer to the classification of monoclonal gammopathies according to serum kappa and lambda concentrations - click here for an explanation of these.
