Background.It is unclear if immunosuppression increases the likelihood of malignant transformation of monoclonal gammopathy of undetermined significance (MGUS) and whether adverse renal outcomes in kidney transplant recipients with MGUS are more frequent.Methods.We performed a retrospective cohort study of kidney transplant recipients at the Centre Hospitalier de l’Université de Montréal between 2000 and 2016.Results.Among 755 study participants, 13 (1.7%) were found to have MGUS before transplant. Two evolved to smoldering multiple myeloma and 2 presented paraprotein-induced allograft injury from light chain deposition disease. Forty-six patients developed posttransplant MGUS (2.5% 5-y cumulative incidence) of which 1 progressed to multiple myeloma and 1 experienced kidney allograft loss from light chain deposition disease. None of the patients with a malignant transformation or paraprotein-induced renal disease after transplantation had had a systematic workup before transplantation to exclude hematologic malignancies and paraprotein-related kidney injury. Nine posttransplant MGUS (21%) were transient. Multivariable analysis revealed that age at transplant (hazard ratio 1.05 per 1-y increase, 95% confidence intervals, 1.02-1.08) and prior cytomegalovirus infection (hazard ratio 2.22, 95% confidence intervals, 1.07-4.58) were associated with the development of MGUS after transplantation. Of 7 posttransplant lymphoproliferative disorders, none were preceded by MGUS.Conclusions.Our results suggest that the identification of MGUS in a transplant candidate should lead to further investigations to exclude a plasma cell neoplasm and monoclonal gammopathy of renal significance before transplantation. MGUS arising after transplantation appears to carry a favorable evolution.

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Multiple myeloma is a disease characterised by the overproduction of monoclonal proteins. Whilst concentration of FLC correlates poorly with tumour burden at diagnosis, changes during treatment are considered to be an accurate and sensitive measure of response. Aggregation of FLC presents a problem for traditional means of FLC estimation, large aggregates will not pass through the kidney making urine unreliable. Objectives : To report follow-up of 2 patients with discrepancy between SPE M-spike and serum FLC, one with serum free lambda, the other with serum free kappa. To analyze and confirm presence of multimer FLC aggregates in these 2 patients. Methods : Routine SPE and immunofixation were performed by capillary electrophoresis (CZE). Serum FLC was measured by nephelometry. FLC polymerisation studies were undertaken by SDS-PAGE, Western blot and Sephadex S-200 gel filtration chromatography. Results: First patient (free lambda) is a 80 y woman with IgA lambda multiple myeloma. Upon treatment, IgA lambda peak fell from 18 g/L down to < 0,4 g/L with a serum free lambda remaining at 10 700 g/L. Monoclonal free lambda peak at CZE was estimated to 1,5 g/L, a 7x discrepancy. High dose Decadron therapy was unsuccessful, serum free lambda remaining about 2500 to 4000 g/L for the next 6 months. Polymerisation studies revealed multiple aggregates of FLC with molecular weight (MW) ranging from 24 000 Da to > 200 000 Da. Second patient (free kappa) is a 70 y old man followed since 1985 for an IgG kappa indolent multiple myeloma. Treatment with melphalan in 1998 caused disappearance of M-spike at SPE and persistant hypogammaglobulinemia. Introduction of FLC testing in August 2006 revealed an unexpected serum free kappa of 2740 g/L which remained stable in the following months. This serum free kappa is not visible by CZE. Polymerisation studies revealed multiple aggregates of FLC with MW ranging from 24 000 Da to > 200 000 Da. Conclusion : Serum FLC measurement is a new biological parameter for investigation and follow-up of monoclonal gammopathies with added value as showed here for 2 myeloma treated patients. One should be aware of well known interferences in FLC measurement such as renal dysfunction and polyclonal hyper-gammaglobulinemia. Here we demonstrated a less well documented confounding factor creating an unexpected discrepancy between this nephelometric technique and traditional CZE/SPE. We showed highly overestimated FLC by nephelometry. We revealed a profile of multiple complexes in 2 cases of FLC (one free lambda and one free kappa) of molecular weight up to > 200 000 Da. These multimers may well impact kidney function and interfere with standard urine investigation. It appears clear to us that an interpretation from an experienced professional should accompany any FLC measurement.