【作者】 马岩；

【导师】 林玉梅；

【作者基本信息】 吉林大学 ， 临床医学， 2008， 硕士

【摘要】 目的:通过对多发性骨髓瘤(multiple myeloma,MM)患者临床资料的分析,进一步明确MM肾损害发病的基本临床规律,确立MM肾损害的危险因素。方法:收集2003～2007年在我院收治的MM患者共162例。逐一记录患者确诊时的性别、年龄、骨髓浆细胞百分数、尿本周蛋白(Bence Jones protein,BJP)、血清M蛋白水平、血红蛋白(Hgb)、血清β2-微球蛋白(β2-MG)、白蛋白(ALB)、球蛋白(GLB)、碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)、钙(Ca)、磷(P)、尿酸(URIC)、骨骼损害、肾脏超声等临床和实验室指标。将患者按DS分期标准分为非肾损害A组与肾损害B组,对其临床表现、各项实验室指标等方面进行分析,并评价DS、ISS两种分期系统与MM肾损害的相关性。两组间计数资料的比较用χ2检验;计量资料的比较用t检验。使用SPSS13.0软件包完成。P≤0.05,差异有统计学意义。P≤0.01,差异有显著统计学意义。结果:我们分析了162例MM患者的临床资料及实验室指标,其中肾损害的发生率为34.6%。年龄、性别与MM肾损害无明显相关性。B组患者的骨髓浆细胞百分比、血M-蛋白、ALB、GLB、ALP、LDH水平较A组无明显升高或降低,差异无显著性(P>0.05)。B组患者尿BJP阳性率、血β2-MG、血URIC、血Ca、血P水平较A组明显升高,两组相比差异有显著性(P值分别为<0.005,=0.004,<0.01,<0.01,<0.01)。B组患者血红蛋白水平较A组明显下降,差异有显著性(P=0.002)。ISS分期系统与肾损害的相关性(P=0.030)优于DS分期系统(P=0.405)。MM肾损害与骨损害无明显相关性。MM肾损害双肾一般呈弥漫性损害表现,体积无明显增大或缩小。结论:本研究进一步证实了尿BJP、血β2-MG、血Ca、血URIC、Hgb、血P的水平与MM肾损害的相关性,其中血β2-MG可能是最主要的预测因子。并于国内外首次提出了MM ISS分期与肾损害的相关性优于DS分期系统。更多还原

【Abstract】 Multiple myeloma is a vicious monoclonal B-cell disease with plasmacyte proliferating., the monoclonal B cells capable to produce a large number of abnormal immunoglobulins orκ、λlight chains(monoclonal protein,M- protein). The incidence has been the twice position in hematological malignancy..It often occours in middle and old aged people. The incidence rate of this disease has been rising recently . Bence-Jones proteins are monoclonal immunoglobulin light chains which are excreted in large amounts in the urine. Because the degree of vicious proliferation and range of infiltration are different, and the quantity and denomination of monoclona immunoglobulin for synthesis and excretion are also different, the clinical manifestation is complex and various. Complications of multiple myeloma include renal insufficiency, hematologic complications, bone complications neurologic complications ,infections and so on,. The original symptoms are diversified, misdiagnosis rate is 88.58%.Renal failure is a common complication in patients with multiple myeloma.,Up to 50% of newly diagnosed patients have a decrease in creatinine clearance and approximately 20% of the patients with MM will develop progressive renal failure in the course of myeloma disease.Around two to three percent require dialysis because of severe renal impairment. The causes of renal failure are diverse. Several types of renal disease are observed, Myeloma cast nephropathy is the most frequent and sometimes associated with acute renal failure. AL amyloidosis and monoclonal immunoglobulin deposit disease are often presented as a nephrotic syndrome. The most important mechanism of renal damage is light chain which deposits in renal glomeruli .and activating some response includes phosphorylation of MAPKs and nuclear transcription factors NF- B with ensuing production of inflammatory cytokines, such as TNF- , interleukin-6, 8.This finally results in apoptosis of tubular lining cells.A great quantity free light chain(BJP)are absorbed by renal tuble and deposit in cell plasm of epithelial cells, with accumulation of cell debris, tubular epithelial cells are distension and dysfunction.Quite often renal failure develops rapidly even at an unchanged ratio of production and serum concentration of light chains. Various factors can favour renal cast formationin myeloma patients, such as dehydration ,hypercalcaemia, hyperuricemic, drugs,hyperviscosity, amyloidosis and so on..As for the MM staging system, DS system is the most widely adopted. But this system is complex and can not be better estimate the prognosis Therefore ,in 2005,the International staging system (ISS) for MM was reported on the Journal of Clinical Oncology.The ISS has been described to estimate prognosis using serum beta-2 microglobulin and serum albumin. Compared with the Durie/Salmon staging system , the ISS stage could be better estimate the prognosis and could be a simple alternative to DS stage for patients.To study the clinical features of patients with multiple myeloma accompanied by renal insufficiency , and investigate the related risk factors of renal insufficiency. A control study was performed among 106 patients with normal renal function in MM(group A) and 56 patients with renal insufficiency due to MM (group B).Meanwhile ,we also appreciated the dependability between the renal lesion and the two staging system(DS system and ISS system),we got the following results 1. Epidemiology:Among the 162 MM patients , 94 patients were men and 68 were women, the ratio of male and female was 1.38:1. The age of all the patients ranged from 26 to 80 years old.and 78 percent of them were above 55 years old The median age was 58 years old。There were 106 patients in group A and the ratio of male and female was 1.2:1, The age of them ranged from 26 to 80 years old.and the median age was 59 years old。There were 56 patients(34.6%) in group B and the ratio of male and female was 1.8:1, The age of them ranged from 26 to 79 years old.and the median age was 57 years old。Compared with group A ,there were more male patients and the age of onset were yonger in group B But there were not statistically different(P〉0.05).It indicates that age and sex had no obivious relationship with myeloma kidney.2. The original symptoms and course:Comparing these two groups.the original symptoms were diversified and there was no specificness.The mean course of group B was shorter than group A.The results suggests that the condition of the multiple myeloma patients with renal dysfunction was getting worse more rapidly and the patients visited doctors earlier.3. Main laboratory examination and renal leision:The level ofβ2-microglobulin in group B was significantly higher than that in group A.(P=0.004). The level of serum calcium in group B was significantly higher than that in group A.(P<0.01).The mean Hgb was lower in group B than that in group A,serum uric acid, phosphonium in group B were higher than that in the group A. and the difference was significant.The positive incidence of Bence-Jones proteinuria in group B(83.7%)were higher than that in group A(58.1%),and the difference was significant(p<0.05)It suggests that the high level ofβ2-microglobulin, calcium,Hgb and the positive incidence of Bence-Jones protein have relationgships with renal lesion in patients with multiple myeloma and all of them are the risk factors for the occurrence of renal lesion. The level of the percentage of plasmocyte in bone marrow、serum alkaline phosphatase in group B weie higher than that in group A ,but the serum albumin globe, lactic acid dehydrogenase in group B were lower than that in groupA, the differences were not significant .The percentage of the patients whose level of M-protein were above normal in group B(56.5%)was higher than that in group A(53.1%),but the difference was not significant .4. Immunity classification and renal lesion74(45.7%)cases were IgG type, 44(27.2%)cases were IgA type, 23(14.2%)cases were light chain type, 7(4.3%)cases were IgD type, 2(1.2%)cases were IgM type,12(7.4%)cases was non-secretion type among 162 cases,the major type were IgG and IgA type .light chain and IgG type was correlated with the high ratio of renal lesion .The rate were separately 43.5% and 37.9%.Meanwhile we notice that the incidence of myeloma kidney was also very high in non - secretion type (33.3%) The ratio ofλandκlight chain was 1.17:1 in group B.It indicates that the ratio of the occurrence of renal lesion in patients withλlight chain is higher than that ofκlight chain5. DS system ,ISS system and renal lesion:The incidence rate of renal lesion in III phase and in I,IIphase were separately 36.3%. and 28.9%,but the difference was not significant when using the DS system.The ratio in III phase(34.4%)was obviously higher than that in I,IIphase(15.5%)and the difference was significant when using ISS system So we can conclude that the myeloma kidney has better relationship with ISS system than DS system.In addition,the incidence rate of bone lesion was 89.0% among all the patients ,the ratio in group B(89.1%) was a little higher than that in group A(88.9%).the difference was not significant When renal lesion occurred, it often appeared diffuse lesion and the size of kidney was neither increasing nor shrinking.We have a multi-analysis on the clinical characters of the patients with myeloma renal lesion and the risk factors for the occurrence of renal lesion ,through the aspects of the percentage of plasmocyte in bone marrow , biochemistry ,immunotyping,the morph of kidney ,bone lesion ,clinical phase and so on .In addition ,we propose that the ISS system. has better dependability with meyloma renal lesion than DS system for the first time.Our resercher provide a clinical foundation for better cognition of the genesis mechanism of myeloma renal lesion and the relationship between the renal lesion and the prognosis of multiple myeloma .:更多还原