Monoclonal gammopathy of undetermined significance: an update for nephrologists

Screening for a monoclonal protein is a common part of the assessment of patients presenting with a renal injury. While in the settings of acute kidney injury, chronic kidney disease and proteinuria monoclonal proteins can be associated with significant pathologies such as cast nephropathy, amyloidosis, and light chain deposition disease, they can also be an unrelated finding. The purpose of this review is to provide the nephrologist with an update to the diagnostic assessment and risk stratification of monoclonal proteins to avoid unnecessary investigation and monitoring of those patients with low-risk monoclonal gammopathies.     

Fracture risk in monoclonal gammopathy of undetermined significance.

To assess fractures in monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma, we followed 488 Olmsted County, MN, residents with MGUS in a retrospective cohort study. There was a 2.7-fold increase in the risk of axial fractures but no increase in limb fractures. The pathophysiologic basis for the increased axial fractures should be determined. INTRODUCTION: Multiple myeloma is often preceded by monoclonal gammopathy of undetermined significance (MGUS). Fractures are common in myeloma as a result of lytic bone lesions, generalized bone loss, and elevated bone turnover from excessive cytokine production. Whether fractures are also increased in MGUS is unknown. MATERIALS AND METHODS: In a population-based retrospective cohort study, 488 Olmsted County, MN, residents with MGUS first diagnosed in 1960-1994 (52% men; mean age, 71.4 +/- 12.8 years) were followed for 3901 person-years; follow-up was censored at progression to myeloma. The relative risk of fractures was assessed by standardized incidence ratios (SIRs), and risk factors were evaluated in proportional hazards models. RESULTS AND CONCLUSIONS: Altogether, 200 patients experienced 385 fractures. Compared with expected rates in the community, statistically significant increases were seen for fractures at most axial sites, for example, vertebrae (SIR, 6.3; 95% CI, 5.2-7.5). There was a slight increase in hip (SIR, 1.6; 95% CI, 1.2-2.2) but not distal forearm fractures (SIR, 0.8; 95% CI, 0.4-1.5). The relative risk (SIR) of any axial fracture was 2.7 (95% CI, 2.3-3.1) compared with only 1.1 (95% CI, 0.9-1.4) for all limb fractures combined. In a multivariate analysis, the independent predictors of any subsequent fracture were age (hazard ratio [HR] per 10-year increase, 1.4; 95% CI, 1.2-1.6) and corticosteroid use (HR, 1.8; 95% CI, 1.2-2.6); greater weight at diagnosis (HR per 10 kg, 0.8; 95% CI, 0.8-0.9), and IgG monoclonal protein (HR, 0.7; 95% CI, 0.5-0.97) were protective. Baseline monoclonal protein level, a determinant of myeloma progression, did not predict fracture risk. Thus, the risk of axial, but not peripheral, fractures is increased among MGUS patients even before progression to myeloma. The pathophysiologic basis for this should be determined because elevated bone turnover, for example, might be treatable.     

Successful management of polyneuropathy associated with IgM gammopathy of undetermined significance with antibody-based immunoadsorption

Peripheral polyneuropathies associated with monoclonal IgM gammopathy of undetermined significance often have a progressive course and optimal treatment has not been established. We report on a patient diagnosed with polyneuropathy associated with benign IgM gammopathy, who was successfully treated with antibody-based immunoadsorption only. The neurological symptoms of the patient improved continuously over six months of treatment. Controlled trials should be performed to define this indication for antibody-based immunoadsorption therapy.     

Fibrillary glomerulonephritis associated with monoclonal gammopathy of undetermined significance showing lambda-type Bence Jones protein

A 79-year-old woman was admitted to our hospital because of leg edema due to a nephrotic syndrome. Urinary and serum immunoelectrophoresis showed positive for the lambda type of Bence Jones protein. A bone marrow aspiration test revealed mild plasmacytosis (6.4% of the total cells). These findings confirmed her diagnosis of monoclonal gammopathy of undetermined significance (MGUS). Her renal biopsy specimen revealed mild mesangial cell proliferation and an increase in the mesangial matrix. Immunofluorescence studies showed positive staining for IgG, IgA, C3, and kappa and lambda light chains in the capillary wall and mesangium area. Electron microscopy showed that the electron deposits in the thickened basement membrane were formed by randomly arranged 16- to 18-nm nonbranching fibrils. A Congo red stain for amyloid was negative. These findings corresponded with the diagnosis of fibrillary glomerulonephritis. Therefore, this case showed a rare combination of fibrillary glomerulonephritis and MGUS.     

Monoclonal gammopathy and glomerulonephritis with organized microtubular deposits

We report a case with IgG-kappa monoclonal gammopathy of unidentified significance (MGUS) and glomerulonephritis (GN) with organized microtubular deposits on electron microscopy (EM). Light microscopy (LM) examination showed exudative features and moderate extracapillary proliferation. An acute nephritic syndrome with a rapidly progressive renal failure was clinically manifest at the onset and during each relapse. The patient was treated with methylprednisolone pulses followed by oral prednisone, cyclophosphamide, plasmapheresis, and maintenance courses of chemotherapy. The response to treatment was good, with a temporary improvement of renal function and control of the downhill course over a 3-year follow-up.     

Neoplastic and non‐neoplastic complications of solid organ transplantation in patients with preexisting monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance (MGUS) occurs in 3–7% of the elderly population, with higher prevalence in renal failure patients, and is associated with a 25‐fold increased lifetime risk for plasma cell myeloma (PCM), also known as multiple myeloma. Using the California State Inpatient, Emergency Department, and Ambulatory Surgery Databases components of the Healthcare Cost and Utilization Project (HCUP), we sought to determine whether patients with MGUS who undergo solid organ allograft (n = 22 062) are at increased adjusted relative risk (aRR) for hematologic malignancy and other complications. Among solid organ transplant patients, patients with preexisting MGUS had higher aRR of PCM (aRR 19.46; 95% CI 7.05, 53.73; p < 0.001), venous thromboembolic events (aRR 1.66; 95% CI 1.15, 2.41; p = 0.007), and infection (aRR 1.24; 95% CI 1.06, 1.45; p = 0.007). However, when comparing MGUS patients with and without solid organ transplant, there was decreased aRR for PCM with transplant (aRR 0.34; 95% CI 0.13, 0.88; p = 0.027), and increased venous thromboembolic events (aRR 2.33; 95% CI 1.58, 3.44; p < 0.001) and infectious risks (aRR 1.44; 95% CI 1.23, 1.70; p < 0.001). While MGUS increased the risk of PCM overall following solid organ transplantation, there was lower risk of PCM development compared to MGUS patients who did not receive a transplant. MGUS should not preclude solid organ transplant.     

原发性骨质疏松与多发性骨髓瘤致椎体压缩骨折的临床对比

目的:探究原发性骨质疏松与多发性骨髓瘤继发骨质疏松致椎体压缩骨折的临床特点、实验室检查和影像学表现,分析总结其差异.方法:回顾性分析2013年1月～2021年1月来我院脊柱脊髓外科就诊的132例椎体压缩骨折患者资料,其中经骨髓穿刺病理学检查诊断为多发性骨髓瘤38例(骨髓瘤组),原发性骨质疏松94例(骨质疏松组),均经双...     

Monoclonal gammopathy of renal significance with light‐chain deposition disease diagnosed postrenal transplant: a diagnostic and therapeutic challenge

Patients with light‐chain deposition disease (LCDD) frequently do not meet criteria for myeloma. In such cases, despite low tumor burden, the circulating monoclonal immunoglobulins cause renal damage, are responsible for post‐transplant recurrence, and are rightly categorized as monoclonal gammopathy of renal significance (MGRS) requiring chemotherapy. A 65‐year male with uncharacterized nodular glomerulopathy presented with proteinuria 3 years postrenal transplant. His allograft biopsies were diagnostic of light‐chain deposition disease (likely recurrent), and in the absence of myeloma, he was labeled as MGRS. Based on the limited literature available, he was treated with bortezomib which resulted in normalization of serum‐free light‐chain ratios and resolution of proteinuria. He, however, later succumbed to complications of chemotherapy. This case highlights the diagnostic difficulties in LCDD, the importance of an accurate pretransplant diagnosis, and treatment of the malignant clone, in the absence of which post‐transplant management of recurrence is challenging with poor outcomes.     

Treatment of multiple myeloma

Conventional chemotherapies are no longer the only treatment in multiple myelomatosis. High-dose chemotherapy and autologous transplantation are not curative but do increase relapse-free survival time in young patients. Thalidomide is efficacious in refractory and relapsing myeloma and its evaluation is going on. Curative and preventive treatments of skeletal events, infections and anemia improve quality of life. All together, these strategies imply therapeutic knowledge and choices but allow an about 5-year-long median survival time in modern studies. Treatment options for myeloma now include, not only conventional chemotherapy regimens, but also novel symptomatic drugs and strategies that increase survival and/or quality of life, although they fail to provide a cure. In parallel with this expansion of the treatment armamentarium, physicians must acquire the knowledge needed to select the best treatment for the individual patient. After reviewing the rationale, effectiveness, and safety of each of these treatments, we will discuss the indications that we believe are legitimate.     

Non-secretory myeloma: a rare variant of multiple myeloma

The spectrum of plasma cell neoplasm represents indolent conditions like Monoclonal Gammopathy of Undetermined Significance (MGUS) to more aggressive multiple myeloma and plasma cell leukemia. Non-secretory myeloma comprises less than 01% of this spectrum where serum protein electrophoresis and quantitative immunoglobulins remain essentially normal. We are presenting a case report of this rare variant involving the sternum of an adult male.