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. Hasan Jalaeikhoo 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 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 [12, 13]. Hasan et al.  reported that in a group of 354 patients, serum creatinine levels were (2.04 ± 2.56) mg/dL , range in(0.6–26.6) mg/dL. MacLennan 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 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, the result is similar to those previously reported[12-14]. 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 disease 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 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 34 patients with IgG MM and 22 (68.8%) of the 25 patients with IgA MM in the renal involvement group presented with renal failure. In this group, patients with pure light chain disease (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 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 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 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 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 common renal pathological type of MM are cast nephropathy, light-chain deposition disease and amyloidosis, and sometimes the three pathological types concurrence in the same kidney specimen. However, no coexistence of the three pathological types was observed in this group. 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 Yu-Tai 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. Our data also shows that cast nephropathy has the highest incidence, followed by renal amyloidosis, while light chain deposition disease was not found in any of the patients, which may due to small sample size. The patients of MM underwent renal biopsy for light-chain deposition disease is extremely rare, because of renal injury patterns other than cast nephropathy and amyloidosis can be very silent.
We further analyzed the relationship between clinical phenotypes and results of renal biopsy in the renal involvement group. Cast nephropathy is mostly in stage Ⅱ, 24-h urinary protein and hypercalcemia is more obvious. However, renal amyloidosis is mostly in stage Ⅰ. Literature shows that the composition of urinary protein in MM patients with different renal pathological types is different. The main component of urinary protein in MM patients with cast nephropathy type is light chain, however, 70% of urinary protein in MM patients with renal amyloidosis type is albumin . SU Yu-Tai et al.  reported that renal amyloidosis had the highest 24-hour urinary protein level and was more prone to hypoproteinemia-related manifestations, such as edema, nephrotic syndrome. Nasr SH et al.  reported that kappa chains tend to be more common in MCN and LCDD, which is consistent with our results.