23.3.1 Screening for monoclonal gammopathy in patients presenting with renal dysfunction

Chapter 23

Screening for monoclonal gammopathy in patients with renal impairment is associated with distinct challenges: patients may become anuric, in which case urine measurements become irrelevant, and urine samples are often not provided. For example in one renal screening study, urine samples were only obtained from 24 of 41 myeloma patients [165].

The increased sensitivity of sFLC analysis over urine testing identifies additional monoclonal gammopathies associated with renal disease; Gerth et al. [509] performed a retrospective analysis of a cohort of patients with light-chain associated kidney disease comprising 143 patients with myeloma cast nephropathy, 12 patients with light chain deposition disease (LCDD) and 53 patients with AL amyloidosis. The authors reported that UPE alone detected 96.4% of cast nephropathy patients, 76.9% of AL amyloidosis patients and 55% LCDD patients. This compared with the sFLC ratio sensitivity of 96.8% for cast nephropathy, 100% for AL amyloidosis and 71.4% for LCDD patients.

Use of a renal reference interval for the κ/λ sFLC ratio in routine clinical practice may lead to increased diagnostic accuracy for the diagnosis of monoclonal gammopathy (Section 6.3). The diagnostic utility of the renal reference interval was assessed in combination with SPE/UPE by Park et al. [507] in a retrospective analysis of 471 patients who visited a nephrologist due to unexplained renal impairment. A total of 110 patients (23.4%) were diagnosed with MM, 346 were classed as “non-MM” and the remaining 15 patients had other plasma cell dyscrasias or lymphoproliferative diseases and were excluded from further study. sFLC analysis was particularly effective for screening patients for LCMM (diagnostic sensitivity: 100%), compared with SPE or UPE (diagnostic sensitivity: 58.6% or 69.0% respectively) (Table 23.4). The authors also commented on the difficulty in obtaining 24-hour urine collections (Chapter 24), and the benefit of including sFLC analysis in the initial diagnostic screen: an additional 24/252 (9.5%) CKD patients were newly diagnosed with MM following the introduction of routine sFLC analysis. The authors concluded that a combination of SPE and sFLC analysis (using the renal reference range for the sFLC ratio) was the optimal screening algorithm for detection of MM in patients presenting with renal impairment.

Conventional sFLC ratio
(0.26 - 1.65)
Renal sFLC ratio
(0.37 - 3.1)
Combined analysis: SPE + renal sFLC ratio
(0.37 - 3.1)
All MM (n=110) Sensitivity (%) 81.8 70.2 90.9 91.8 98.2
Specificity (%) 97.5 98.6 89.9 95.1 95.1
IIMM (n=81) Sensitivity (%) 90.1 70.7 87.7 88.9 97.5
Specificity (%) 97.5 98.6 89.9 95.1 95.1
LCMM (n=29) Sensitivity (%) 58.6 69.0 100 100 100
Specificity (%) 97.5 98.6 89.9 95.1 95.1
IIMM: Intact immunoglobulin MM; LCMM: light chain MM.

Table 23.4. Diagnostic sensitivity and specificity of routine laboratory screening tests for MM in patients with renal impairment [507].

Koo et al. [909] studied the diagnostic sensitivity of sFLC analysis in combination with other laboratory tests, to screen for a monoclonal protein in patients who underwent a renal biopsy. For patients with nephrotic syndrome, a panel of sFLC analysis (using the renal reference range) alongside sIFE and uIFE showed 100% diagnostic sensitivity for MM and monoclonal gammopathy of renal significance (Section 26.4.1). Whereas for patients with chronic glomerulonephritis, a reduced panel comprising sFLC + SPE (or UPE + SPE) had 100% sensitivity for MM. The authors concluded that the sensitivity of screening panels varied according to the presenting features of kidney disease.