Long-term data regarding kidney transplantation (KTx) patients with monoclonal gammopathy of undetermined significance (MGUS) are scarce. We evaluated the long-term outcomes of these patients in a single-center retrospective study from the Mayo Clinic, Rochester, Minn., USA.
Patients who had an MGUS before transplant or developed one after KTx were selected. Monoclonal protein was screened as part of the KTx evaluation by serum protein electrophoresis. Screening for posttransplant lymphoproliferative disorder (PTLD) or MGUS after transplant was not required by protocol. Patients with multiple myeloma, dysproteinemia-related kidney disease or no pretransplant serum protein electrophoresis were excluded.
Between 1963 and 2006, 3,518 patients underwent KTx. MGUS was identified in 42 patients, with 23 before transplant and 19 after transplant. Median follow-up for these patients was 8.5 years (range 0.3-37). Four (17.4%) pretransplant MGUS patients developed a hematologic malignancy: 2 smoldering multiple myeloma and 2 PTLD - an Epstein-Barr virus-positive diffuse large cell lymphoma and a Hodgkin lymphoma. None of the 19 patients who developed an MGUS after transplant progressed to multiple myeloma, but 2 (10.5%) developed Epstein-Barr virus-negative T cell lymphoproliferative disorders at 16 and 26 years after transplant. Median survival was 26.1 and 28.0 years for the pretransplant and posttransplant MGUS groups, respectively.
Progression from true MGUS to multiple myeloma is rare after KTx. KTx appears safe in true MGUS patients if the monoclonal gammopathy was not the cause of the kidney disease. None of the patients progressed to multiple myeloma, but 2 developed smoldering multiple myeloma and several developed PTLD. Further studies are needed to explain the relationship between MGUS and PTLD.
[Show abstract][Hide abstract] ABSTRACT: Transplant recipients have elevated risk for plasma cell neoplasms (PCNs, comprising multiple myeloma and plasmacytoma), but little is known about risk factors in the transplant setting. Through linkage of the US solid organ transplant registry with 15 state/regional cancer registries, we identified 140 PCNs in 202 600 recipients (1987-2009). PCN risk was 1.8-fold increased relative to the general population (standardized incidence ratio [SIR] 1.80, 95%CI 1.51-2.12). Among cases, 102 were multiple myeloma (SIR 1.41) and 38 were plasmacytoma (SIR 7.06). PCN incidence increased with age, but due to the rarity of PCNs in younger people in the general population, SIRs were highest in younger transplant recipients (p = 0.03). PCN risk was especially high in recipients who were Epstein-Barr virus (EBV) seronegative at transplantation (SIR 3.93). EBV status was known for 18 tumors, of which 7 (39%) were EBV positive. Following liver transplantation, PCN risk was higher in recipients with cholestatic liver disease (SIR 2.78); five of these cases had primary biliary cirrhosis (PBC). A role for primary EBV infection after transplantation is supported by the increased PCN risk in young EBV seronegative recipients and the presence of EBV in tumors. PBC may be another risk factor, perhaps by causing chronic immune activation.
American Journal of Transplantation 05/2013; 13(6). DOI:10.1111/ajt.12234 · 5.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Kidney injury is a common complication of multiple myeloma and other plasma cell dyscrasias, and it is associated with increased mortality. Multiple pathogenic mechanisms can contribute to kidney injury in the patient with myeloma, some of which are the result of nephrotoxic monoclonal Ig and some of which are independent of paraprotein deposition. The pathogenic mechanisms that underlie paraprotein-related kidney disease are increasingly well understood. A novel assay allowing the quantification of free light chains in the serum has aided the diagnosis of new onset disease and allowed for the earlier detection of relapse. Novel myeloma agents have shown considerable promise in reversing renal failure in some patients and improving outcomes. Stem cell transplantation remains a mainstay of management for younger patients with myeloma who are suitable candidates for intensive therapy, whereas the role of new drugs, plasma exchange, and kidney transplantation continues to evolve.
Clinical Journal of the American Society of Nephrology 07/2013; 8(11). DOI:10.2215/CJN.12231212 · 4.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Proteinuria is an expected complication in transplant patients treated with mammalian target of rapamycin inhibitors (mTOR-i). However, clinical suspicion should always be supported by histological evidence in order to investigate potential alternate diagnoses such as acute or chronic rejection, interstitial fibrosis and tubular atrophy, or recurrent or de novo glomerulopathy. In this case we report the unexpected diagnosis of amyloidosis in a renal-transplant patient with pre-transplant monoclonal gammapathy of undetermined significance who developed proteinuria after conversion from tacrolimus to everolimus.
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