The spot urine protein/creatinine ratio is a simple, rapid and inexpensive method for monitoring patients with light-chain multiple myeloma.

Protein electrophoresis of a 24-h urine collection (UPEP) is considered the standard method for following up patients with light-chain multiple myeloma [1]. The serum-free light-chain assay (SFLCA) has increasingly been used in this population [2], and in individual patients tracks well with proteinuria [3]. In addition, the SFLCA is also generally more sensitive than urine studies including immunofixation electrophoresis for detecting minimum residual light-chain disease [4,5]. However, the SFLCA is expensive, and due to inter-patient variation in the renal metabolism of light chains, the amount of proteinuria cannot be predicted by the SFLC concentration [1,5-7]. As proteinuria correlates better with renal dysfunction than SFLC and may be caused by factors other than light chains, serial measurement of urinary proteinuria is still considered essential [7].

The spot urine protein/creatinine ratio (SUPCR) has increasingly replaced the 24-h urine in patients with proteinuria from a variety of causes [8], but has not been examined in patients with multiple myeloma. As free light chains have a half-life of 2–6 h [9], the SUPCR is theoretically ideally suited to measure response to treatment within days of beginning therapy, and moreover, can be inexpensively and serially measured with rapidly available results. In this report, five patients with predominantly light-chain multiple myeloma were followed up by SUPCR and SFLCA. In Patient 1 and 2 (Figure 1A and B), progressive disease and subsequent response to therapy were accurately detected by SUPCR and in agreement with changes in the SFLCA. In Patient 3 (Figure 1C), bortezomib was added to thalidomide and dexamethasone because of worsening renal insufficiency. Serial SUPCR demonstrated that the proteinuria decreased after each cycle of bortezomib followed by a rebound during each 10-day rest period. The changes in the SUPCR grossly paralleled changes in SFLC levels. A bone marrow examination showed extensive replacement by multiple myeloma, confirming treatment resistance.

Fig. 1

Spot urine protein/creatinine ratio and involved serum-free light chain (FLC) in response to therapy. (A) Patient 1: Because of worsening proteinuria and renal insufficiency (creatinine 2.5 mg/dL), bortezomib was started followed by a rapid decrease in proteinuria and κ FLC. (B) Patient 2: After a brief decrease in proteinuria after cyclophosphamide/etoposide/dexamethasone chemotherapy, there was disease progression with no response to pulse dexamethasone followed by a sharp decrease in proteinuria and κ FLC after starting lenalidomide. (C) Patient 3: After bortezomib was added to thalidomide/dexamethasone, there was a decrease in proteinuria and λ FLC followed by a rebound after each 10-day rest period. Bortezomib (B) was given as four doses on Day 1, 4, 8 and 11 of each 21-day cycle. Spot urine protein/creatinine is reported as milligram per milligram. Serum-free light chains are reported as milligram per decilitre. Upper limit of normal for κ FLC is 1.94 mg/dL, and for λ FLC is 2.63 mg/dL. The dotted line on the x-axis represents the upper limit of normal (<0.3 mg/mg) of the spot urine protein/creatinine ratio.

Patient 4 had three consecutive SFLCA in which the free kappa light-chain levels were mildly increased, ranging from 14.2 to 15.3 mg/dL (nl <1.94 mg/dL). During this same interval, two SUPCR samples were dramatically elevated at 5.2 and 6.0 mg/mg (nl <0.3 mg/mg). UPEP of the spot urine sample showed that 79% of the proteinuria was monoclonal. As the monoclonal proteinuria was disproportionately higher than the mildly abnormal SFLCA results, the SFLCA was repeated utilizing higher dilutions, and the correct SFLC concentration was found to be ~10-fold higher. The falsely low results were attributed to ‘antigen excess’ [10].

Patient 5 was referred with lambda light-chain myeloma and deteriorating performance status. At her first visit, the free lambda light chain was 90 mg/dL (nl <2.63 mg/dL), but the SUPCR was markedly increased at 5.7 mg/mg. UPEP of the spot urine showed that most of the protein was albumin indicative of a glomerular lesion. A skin biopsy showed amyloid.

These preliminary results suggest that the SUPCR can be used to monitor response in patients with light-chain proteinuria and, in contrast to SFLCA, may detect other causes of proteinuria that can be further evaluated by electrophoresis. The SUPCR can also identify patients in whom the SFLCA is falsely low due to antigen excess.

Conflict of interest statement. None declared.