MM is an age-related disease. In most studies, the reported age at onset is approximately 65 years. Palumbo A et al. reported only 37% of patients with newly diagnosed disease are aged < 65 years, 26% are aged 65-74 years, and 37% are aged ≥ 75 years. Jalaeikhoo H et al. reported the mean age was 61.98 ± 11.44 years (range = 30–88 years), and the male: female ratio was 1.73. Our results were consistent with these findings: in our study, the median age at onset was 63 years, and the male: female ratio was 1.5:1. The youngest patient in our study was 36 years old.
In our study, 90(45.0%) patients were admitted to the Department of Nephrology. And MM patients with renal involvement as the first symptom often do not exhibit the typical clinical manifestations of myeloma, such as hyperglobulinemia. From the Table 2, we could find that patients with renal involvement had a lower globulin level than the levels in patients without renal involvement. In the non-renal involvement group, 17(20.5%) patients presented with bone pain as the first manifestation and were admitted in the Department Orthopedics. Other patients were admitted in the Departments of Oncology, Cardiology, Ophthalmology, Neurology, etc. The reason for this diversity in symptoms is that amyloid deposition in different organs or tissues causes dysfunction of these organs and tissues and leads to specific symptoms. In an analysis of light chain deposition disease (LCDD), Pozzi C et al. found that 35% of LCDD cases were associated with extrarenal manifestations involving the heart (21%), which presented as congestive heart failure and arrhythmias, and the liver (19%), which could lead to portal hypertension. Involvement of the lung (pulmonary cystic disorder), gastrointestinal tract and neurological system was less frequent. The above findings indicate that the presenting symptoms of MM are diverse and can easily be misdiagnosed; therefore, every physician should be familiar with these symptoms.
Renal failure in MM is one of the most common complications, and 50% of MM patients are reported to have renal failure at the time of diagnosis[16, 17].Jalaeikhoo H et al. reported that in a group of 345 patients, serum creatinine levels were (2.04 ± 2.56) mg/dL , range in(0.6–26.6) mg/dL. MacLennan IC et al. reported that in a group of 1,205 patients, serum creatinine levels were >130 μmol/l in 42% of patients, >200 μmol/l in 20% and >300 μmol/l in 12%. Korbet SM et al. reported that renal insufficiency (serum creatinine of ＞1.3 mg/dl) is found at presentation in almost 50% of patients with myeloma, and severe renal insufficiency (serum creatinine＞2.0 to 2.5 mg/dl) is seen in ＞15 to 20% of cases . In our study, however, the most common type of renal involvement was proteinuria and/or hematuria, followed by renal failure. In all, 94 (47.0%) patients presented with renal failure (including26[13%]patients presented with AKI, the result is similar to those previously reported[16-18]. Moreover, MM patients with renal involvement had a higher degree of anemia, hypercalcemia and hypertension than patients without renal involvement. The incidence of stage III disease was also significantly higher in the renal involvement group than in the non-renal involvement group. These data suggested that MM with renal involvement is a more serious condition, and this conclusion is consistent with the findings of other studies. Suzuki K et al. reported that hypercalcemia associated with osteolysis by myeloma cells is also causes of renal dysfunction.
We were analyzed the relationship between renal involvement and the results of immunofixation electrophoresis. In total, 182 patients, of which 135 were in the renal involvement group, underwent immunofixation electrophoresis. IgG, IgA, IgD, IgE nonsecretory and simple light chain was present in 52, 32, 1, 1, 4 and 45 patients, respectively, in the renal involvement group. IgG and IgA MM was found in 24 and 18 patients in the non-renal involvement group. Greipp PR et al. reported the immunophenotyping results of 10,750 MM patients. They found that the IgG type accounted for 60% of patients, while the IgA, IgD and light chain types accounted for 24%, 3% and 11% of patients; the remaining 2% of patients had other immunophenotypes. Immunofixation electrophoresis of large samples of MM serum from abroad showed that IgG type accounted for 52%, and the IgA, IgM, IgD, kappa, and lambda types accounted for 21%, 0.5% , 2%, 9% and 7% of patients. Our results were similar to these findings; the main immunophenotype of MM was IgG, followed by IgA and pure light chains.
Next, we analyzed the association of immunofixation electrophoresis results with clinical phenotype in patients with renal involvement. We found that 19 (36.5%) of the 52 patients with IgG MM and 22 (68.8%) of the 32patients with IgA MM in the renal involvement group presented with renal failure. 11(21.2%) patients with IgG MM were presented with AKI. In this group, patients with pure light chain types (n = 45) presented with massive proteinuria and renal dysfunction, and 20 (44.4%) of these patients had a 24-h urinary protein excretion of >3.5 g/24 h. Korbet SM et al. reported proteinuria is observed in ＞ 80% of cases, it most often consists of light chains, and light-chain proteinuria can be massive (＞10 g/d) , which was higher than our study. In the literature, MM presenting as nephrotic syndrome is not common, although light chain and IgD MM can present as nephrotic syndrome. It has been reported that patients of MM produce only light chains account for 40–60% of severe myeloma-associated kidney injury .Consistent with this, our data also showed that patients with pure light chain MM were more prone to renal failure. The major cause of renal failure in patients with pure light chain disease is the overproduction of nephrotoxic light chains. Heher EC et al. reported that mechanisms are the result of nephrotoxic monoclonal Ig deposition in the kidneys and others are independent of Igs. However, in our data 36.5% patients with IgG MM and 68.8% patients with IgA MM in the renal involvement group presented with renal failure, indicating that the development of renal failure is not dependent solely on the concentration of light chains. Wirk B et al. reported that patients with large amounts of serum free light chains can have normal renal function, and patients with small concentrations of serum free light chains can present with renal failure. IgD and IgE overproduction is rare in MM. Only one patient in our study had IgD and IgE MM, which manifested as isolated proteinuria and renal failure. Tsakiris DJ et al. reported that IgD MM is almost invariably associated with Bence Jones light chain proteinuria and renal failure.
Renal biopsies in MM patients with renal dysfunction help defining the types of renal injury, which can influence the extent of aggressive therapy and predict possible outcome.The single center of Mayo Clinic analyzed 190 cases of multiple myeloma kidney pathology, and the results showed that MCN accounted for 45%, renal amyloidosis 29%, and light chain deposition 26%.Su YT et al. reported that the 46 cases of MM, cast nephropathy, renal amyloidosis and light-chain deposition disease accounted for 52.2%, 32.6%, and 4.3% patients, respectively. In our data, 9 patients with renal involvement were performed renal biopsy, cast nephropathy and renal amyloidosis were proved in 5 and 4 patients, respectively. 4（80.0%）cases of light chain cast nephropathy were presented with AKI .
The main limitation of our study was that there was small sample size underwent renal biopsy. In our cohort, if a clinical diagnosis have already been established by other ways(eg, diagnosis of MM based on bone marrow findings and lytic bone lesions), nephrologist may not recommend MM patients with renal involvement undergo renal biopsy. Diagnosis of multiple myeloma does not require renal biopsy, however, a biopsy based diagnosis is important in the evaluation of patients with myeloma because each of the renal lesions has its own therapeutic and prognostic implications. In the future, we will recommend that MM patients with renal involvement undergo routine renal biopsy in our department. Another limitation of our work was that our study was lack of the clinical follow-up data of MM patients. The effect of immunosuppression on both renal disease and the hematologic disease and the prognostic effect of different clinical and histopathological parameters in predicting end-stage renal disease were not discussed. Basit A et al. reported that ISS stage and renal failure have a significant impact on prognosis of MM patients. In our study the most common type of renal involvement was isolated proteinuria and/or hematuria. Is there also a bad renal prognosis among those patients who present with isolated proteinuria and/or hematuria at onset ? In future, we need to collect follow-up data and assess the prognostic significance of these clinical parameters.