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29.2. sFLC assays support a diagnosis of LCDD

Chapter 29

A diagnosis of LCDD should be suspected in all cases of renal insufficiency of unknown origin. Whilst a definitive diagnosis of LCDD is based on renal biopsy with thorough histological examination and electron microscopy [642], sFLC analysis should be included in the initial laboratory testing algorithm as the majority of patients have monoclonal sFLCs. This was demonstrated by Katzmann et al. [134] for 18 LCDD patients who were included as part of a larger study aimed at evaluating different serum- and urine-based diagnostic algorithms. The analysis showed that sFLC testing alone, or a panel of serum protein electrophoresis (SPE) and sFLCs, were both as sensitive (14/18; 77.8%) for LCDD detection as a panel of SPE, serum immunofixation electrophoresis (sIFE) and urine IFE (uIFE). Guidelines published by the International Myeloma Working Group (IMWG) [20] recommend the use of sFLC analysis in combination with serum electrophoresis to screen for monoclonal gammopathies, with the exception of AL amyloidosis which additionally requires a 24-hour uIFE. Screening algorithms are discussed further in Chapter 23 and guidelines are detailed in Chapter 25.

The above study by Katzmann et al. [134] supports two previous studies by the same authors in which the diagnostic sensitivity of sFLC analysis in LCDD was evaluated. In one study [19], 89% (17/19) patients with LCDD had an abnormal κ/λ sFLC ratio, including 6/7 patients who were negative by sIFE (Table 29.1). One sample was negative by sFLC analysis but positive by sIFE. In a subsequent publication, seven further patients were studied and all had abnormal κ/λ sFLC ratios [343].

Classification
Elevated
FLC
Abnormal
FLC κ/λ ratio
sIFE κ +ve 8/9 8/9
sIFE λ +ve 3/3 3/3
sIFE -ve; uIFE κ +ve 4/4 4/4
sIFE and uIFE -ve. BMPCs κ +ve 1/3 2/3
Total abnormal for sFLCs1617

Table 29.1. Detection rates by sFLCs in 19 LCDD patients [19]. BMPC: bone marrow plasma cells.

The diagnostic sensitivity of sFLC analysis for LCDD demonstrated above by Katzmann et al. has similarly been shown by other researchers. In the largest single-centre series of renal MIDD published to date, Nasr et al. [638] reported that κ/λ sFLC ratios were abnormal in all patients tested (43/43 LCDD, 4/4HCDD and 4/4 LHCDD) and markedly abnormal (<0.125 or >8) in 78% of these. Cohen et al. [645] also reported abnormal sFLC ratios in 100% of patients (n=32). In a further study of 17 patients with biopsy-proven LCDD, Wechalekar et al. [646] found that 33% more patients with LCDD were identified by an abnormal κ/λ sFLC ratio than by standard electrophoretic methods, and concluded that sFLC analysis was a useful addition to electrophoretic tests when screening for LCDD. An early diagnosis can be clinically valuable as rapid treatment is fundamental for improving patient outcomes [647]. Clinical case history 1 illustrates the clinical sensitivity of the FLC tests compared with conventional serum and urine electrophoretic assays in a patient with LCDD and renal impairment.

Clinical case history 1


Light chain deposition disease undetectable by conventional electrophoretic assays [648].


A 66-year-old man suffering from asthenia and anaemia was investigated for serum protein abnormalities. SPE, sIFE and uIFE tests showed no evidence of monoclonal immunoglobulins (Figure 29). Serum immunoglobulin concentrations were normal/low: IgG 8.5 g/L; IgA 0.4 g/L and IgM 0.2 g/L. However, sFLC concentrations were highly abnormal: κ 294 mg/L; λ 71.6 mg/L and κ/λ ratio 4.1. These results indicated a monoclonal gammopathy and renal impairment. In this patient, sFLC analysis allowed the detection of monoclonal FLCs and supported the clinical diagnosis of LCDD obtained by renal biopsy.



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