The Evolution of Monoclonal Gammopathy of Undetermined Significance in Kidney Transplant Recipients

Abstract

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.

The clinical and pathological features of plasma cell myeloma post solid organ transplantation

“…In a large retrospective study, Goebel et al found that individuals with MGUS pre‐transplant did not have an increased risk of developing PCM post‐solid organ transplantation, and Jimenez‐Zepeda et al have argued against routine testing for MGUS before transplantation as it lacks prognostic value 59,60 . No increase in the risk of progression of PT‐MGUS to PCM has also been documented by several investigators 56,57 . Moreover, spontaneous resolution of MGUS has been reported in 21%‐37% of solid organ allograft recipients, compared to 2% of non‐transplant patients 56,57,61 .…”

“…55 in the general population, with a 30% 25-year cumulative probability of progression to MM. 12 The 5-year cumulative incidence of MGUS in solid organ allograft recipients has ranged from 4% to 10.7% and a prevalence of 8.1% has been reported, [56][57][58] which is higher than the general population. Serum paraprotein analysis prior to organ transplantation was only performed for one patient in our series and the possibility of before transplantation as it lacks prognostic value.…”

“…59,60 No increase in the risk of progression of PT-MGUS to PCM has also been documented by several investigators. 56,57 Moreover, spontaneous resolution of MGUS has been reported in 21%-37% of solid organ allograft recipients, compared to 2% of non-transplant patients. 56,57,61 This difference might relate to distinct (non-neoplastic) etiology of the majority of PT-MGUS cases, i.e., viral infection (EBV, CMV, HHV8) and immunosuppression, especially after monoclonal anti-CD3 antibody therapy, which is thought to decrease T cell control of B cell proliferation.…”

“…56,57 Moreover, spontaneous resolution of MGUS has been reported in 21%-37% of solid organ allograft recipients, compared to 2% of non-transplant patients. 56,57,61 This difference might relate to distinct (non-neoplastic) etiology of the majority of PT-MGUS cases, i.e., viral infection (EBV, CMV, HHV8) and immunosuppression, especially after monoclonal anti-CD3 antibody therapy, which is thought to decrease T cell control of B cell proliferation. 56,[61][62][63] Although four of our PT-PCM patients had antecedent MGUS, evaluable patients with SMM and two with isolated MGUS showed no evidence of disease progression during the study period.…”

Kidney Transplantation and Monoclonal Gammopathy of Undetermined Significance

“…In their series of 755 kidney transplant patients over 16-y period, a group from Montreal performed pretransplant serum protein electrophoresis (SPEP) in 375 patients, whereas 380 patients had SPEP only after kidney transplantation. 12 Thirteen out of 375 patients were identified with MGUS before transplant with 4 of these patients progressing to either smoldering multiple myeloma or light chain deposition disease posttransplantation. Forty-three patients in their cohort were diagnosed with MGUS posttransplantation with only 2 patients progressing to either multiple myeloma or light chain deposition disease.…”