Severe renal impairment changes the dynamics of FLC clearance. As GFR reduces, the clearance of FLCs decreases and becomes more dependent upon the reticulo-endothelial system, which shows no size preference and clears both κ and λ FLCs at the same rate. Therefore, as renal impairment increases, the serum half-life of κ FLCs approaches that of λ FLCs and their serum levels become more influenced by their underlying production rates. Consequently, the increase in the concentration of κ sFLCs is greater than λ sFLCs, and in a minority of patients the κ/λ ratio can increase above the normal reference interval in the absence of monoclonal gammopathy. This was demonstrated in a study using Freelite on serum samples from 688 patients with chronic kidney disease (CKD) and no evidence of monoclonal gammopathy 
. As both κ and λ sFLC concentrations increased in patients with deteriorating renal function, their relative amounts changed slightly (Figure 6.3A)
. As a consequence, with increasing CKD stage, the median sFLC ratios were found to increase progressively from 0.6 to 1.1, with a 100% range of 0.37 - 3.10 (Figure 6.3B)
. Therefore, a κ/λ sFLC reference interval of 0.37 - 3.10, termed the "renal reference interval", was proposed for patients with renal impairment 
. A similar trend was observed by Galvani et al. 
The diagnostic accuracy of the Freelite renal reference interval was assessed in an unselected group of 142 patients who presented with dialysis-dependent acute kidney injury (AKI) of unknown cause 
. All 41 patients with MM had abnormal κ/λ sFLC ratios by both the published reference range and renal reference range (Figure 6.4)
. Receiver operating characteristic (ROC) analysis showed that application of the renal reference range for the ratio increased the specificity from 93% to 98% with no loss of sensitivity. The diagnostic utility of the κ/λ sFLC renal reference range was further demonstrated by Park et al. 
. A combination of sFLC analysis (using the renal reference interval) in combination with SPE, was the optimal screening algorithm for detecting MM in patients with renal impairment (Section 23.3.1
, Table 23.4).
Palladini et al.  studied the performance of the renal reference interval in 982 newly diagnosed AL amyloidosis patients of whom 16% (160/982) had severe renal dysfunction (eGFR<30 mL/min/1.73m2). Use of the renal reference interval in patients with renal failure improved the overall diagnostic sensitivity from 70% to 74%. This was due to an increase in the diagnostic sensitivity in patients with λ clones, but a decrease in the performance in κ clones. The authors concluded that "patients with AL amyloidosis and severe renal failure whose κ/λ sFLC ratio is <0.37 likely harbour a λ clone".
In conclusion, use of the Freelite renal reference interval in routine clinical practice may lead to increased diagnostic accuracy for the diagnosis of monoclonal gammopathy. For patients with CKD, a κ/λ sFLC ratio of 1.66 - 3.1 is likely to be caused by the change in FLC clearance and further investigation is only warranted if there is a significant clinical suspicion of monoclonal gammopathy.