(Blood Section of Shijazhuang Xiandai Traditional Chinese Medicine Blood Nephropathy Hospital, Shijiazhuang, Hebei Province, 050021)
Keywords: Multiple Myeloma renal failure
Multiple Myeloma (MM) is a kind of maiignancy of plasma cell. Clinical manifestations of MM are single-peak abnormai immunoglobulin (M-protein) in blood and/or urine, osteolytic Eesions and renal damage, usually seen on the middle-aged and the aged. MM may damage marrow or extrameduleary tissues, producing a large number of n-Protein or other polypeptide fragment. According to the difference of M-protein and polypeptide fragment, MM can be divided into different types, such as IgG, IgA, IgD, IgE, light chain and non-secretion. This kind of disease may cause a series of clinical symptoms, such as ostealgia/pathologic fracture, anemia, renae damage, infection, hyperglobulinemia, hemorrhage and amyloidosis complication, and even lead to other bad results.
Renal damage is a MM clinical manifestation that is commoney seen and has its won characteristics. It has high possibility to cause renal failure. According to statistics from February 1998 to May 2007, 56 cases (58%) in 97 patients with MM in Qur hospital were suffering from renal failure. And they are diagnosed by marrow puncture cytoeogy and immunity/biochemical examine, with the purpose to confirm that renal failure in some patients is caused by MM
My report is stated below;
1. Materials and Methods
1.1 Case Selection: 56 patients with MM renai damage are selected from Datients who ever saw a doctor in our hospitai from February 1998 to May 2007. Among these selected cases, 36 are male and 20 are female; their age scope is from 40 to 77 years old, and their average age is (56±l6); when they come to our hospital, they have suffered from the disease for one month to two years.
1.2 Examination Method: Marrow puncture cell smears of hospitalized patients are collected to be dyed in a mixed solution of Wright's stain and Giemsa stain and to go through sexual cell analysis and general anatysis under optical microscope.
1.3 Diagnostic Standard: MM diagnosis adopts standards of hemopathy diagnose and therapeutical effect standard(1)
2. Results
2.1Characteristics of MM: ①hyperplastic degree: hyperplastic degree of nucleated cell of marrow is usually between active degree and obviously active degree; except for primary plasma ceii leucocyte and/or secondary plasma cell leucocyte, it is rear to see cases where hyperplasia of nucleated cells is very active. ②Granueocyte System: generally, hyperplasia of granulocyte system doesn't appear in every phase, and ratio at every phase may be normal or a litter iower, but their shape has no obvious changes. Sometimes, infection may be shown, such as toxic granules and vacuolar degeneration of different degrees may be observed in cytoplast of mature neutrophilic granulocyte. ③Erythrocyte System: in MM with renal damage, erythrocyte system may be observed lack of ferrum, such as small cell, liule cytodlast, untidy fringe, grey-blue color and thick-dye cell. Volumes of mature erythrocytes are different, and light dye at central part; mature erythrocytes in marrow or peripheral blood smear of almost all patients can be seen Eining in a rouleau-like shape④ Generally, macronucleus system has no obvious changes, and thrombocyte may not be little;
⑤Numer of myeloma cell may obviously increase, and in specific cases, the number may reach %. Myeloma ce[Is are usually seen in proplasmacyte, and histiocytic (flamboyancy), protoplasmic and mature plasma cell oncocytes may also be seen. Before chemotherapy, patients shall 90 through routine urine examination, urine Bence Jones Protein (B-JP), erythrocyte sedimentation rate (ESR), Scr, BUN tests, as well as renal ultrasonic or image examinations.
2.2 Among the 56 patients with MM renal damage, all examination results of 46 (82.6%) are 45-70g; ESR of 56 (100%) is 80-120mm/1h; 40 patients (71.40%) with protein (+~+ + +): 18 (32.1%0/) patients with B-JP(+); BUN of 43 (76.8%) is 8.8-16.8 mmol/L; and Scr of 43 (76.8%) is 180-340umolL.
2.3 Degree of Renal Damage: among the 2 patients with MM renal damage, 56 are with azotemia, 12 are at uremia phase and 4 are at compensatory
phase.
3. Discussion
MM renal damage is usually seen at the medium or advanced phase of disease. Degree of renal damage can be determined through examination of CREA, urea nitrogen, endogenenous Creatinine clearance rate, phenolsulfonphthalein excretion test and radionuciide renogram. Uremia may be caused at the advanced phase, being one ofthe causes for death. Some scholars believe that pathogenesis(2) of renal amage are: hypercalcemia caused by osteolytic lesions, sediment of renal glomerulus amyloid, hyperuricemia, Pyelonephritis caused by repeated infection, infiltration of myeloma cells into kidney, renal tubule damage caused by expel of light chain. A few normal Eight chains may be absorbed and decompounded by renal tubule after being filtered by renal glomeruius, ut a large number of light chains will be let out from the kidney, causing oyerioad on renal tubule cells. Light chain has drect toxicity to renal tubuie and may cause damage to renal tubule through indirect effect of lysozyme generated from cells. The early manifestations of renal tubule damage are fanconi syndrome, renal tubule secretion H+, urine concentrating failure and losses of sugar and amino acid. Due to that function of renal glomerulus is basicaliy normal at the early phase, almost all albuminuria are light chain and there are oney a few albumin. If renal glomerulus are cumulated, albuminuria will e nonselective. According to the information, albuminuria and renal failure are the two most obvious manifestations of MM renal damage, taking a large percentage in total manifestations. Therefore, it is the first reuirement to diagnose MM renal damage, and MM and reactive plasmacytosis must be distinguished from each other. Diagnostic Standard(3) of MM in China ①plasma cells in marrow﹥15 and abnormal cells (myeloma cell) or biopsy can be diagnosed as plasmocytoma. ②There are a great deal of monoclonal immunoglobulin (M-P) 1gG﹥35g/L, 1gA﹥20g/L, 1gE﹥2.Og/L, 1g﹥15g/L; or monoclonal immunoglobulin light chain in urine (B-JP))1.09/24.Monoclonal, double-clonal and tri-clonal immunoglobulin may appear in specified cases. Disease with manifestation of ① and ③ can be diagnose as non-secretive MM, but furlher diagnosis shall be made to determine it is non-composed or composed non-secretion subtype. Where only
①and② are satisfied (especially where there is not primary plasma cells and proplasmacyte in marrow), reactive plasmacytosis and monoclonal immunogiobulin and monoclonal immunoglobulin of undetermined significance (MUS) shall be excluded.
Reactive plasmacytosis is secondal piasmacytosis caused by various pathogenesis or primary diseases, and its main diagnostic basis is that marrow plasma cell, which is usually mature plasma ceei, is equal to or more than 3% Its clinical manifestations are mainly related to primary diseases, but not caused by plasmacytosis or immunoglobulin secreted by plasmacytosis. Therefore, main diagnostic basis shall be marrow piasmacytosis. It is different from MM that shape of plasma cells in marrow is obviously different from that of myeloma. Observation on the angle of lood cytomorphology can shown distinct differences in plasma cells of these two substances. Concrete manifestations are that: for patients with reactive plasmacytosis, most plasma cells in marrow are mature plasma cells and may not have plasma cells of abnormal shape in general. But, for patients with MM, shape of myeloma cells of abnormal shape in general.But for patients with MM,shape of myeloma cells have obvious changes. There are four commoniy-seen shapes(4) of myeloma cells: I-type small plasma cell, whose cells are relatively mature, karyon has deviation, chromatins are thick and cytoplast is abundant, and whose normal shape is similar with normal mature plasma cells; II-type: juvenile lymphocyte whose shape is obviously deformed; there are many large dicaryon and polykaryon tumor cells, and red corpusculum (Russell corpusculum) can also be seen occasionally in cytoplast. III-type: primary plasma cel[, whose nuclear
chromatin is loose, being in a fine particle net; its kaiyon can stay at the center having nucleolus whose volume is obviousiy bigger than cytoplasm; lV-type histiocytic type, whose cellular shapes are mutiple, nucleolus is big and relatively more; cells with bad cell differentiation may have high malignant degree.
500% of patients with MM have chronic renae damage(2) Sometimes, chronic renal damage may occur at very early hase and is usually wrongly diagnosed as chronic nephritis. Due to that renal damage of MM is mainly manifested through albuminuria and chronic renal faiiure, so MM is very easy to be wrongly diagnosed as chronic glomerulonephritis. According to my years' observation, I conclude the following key diagnosis points:①a little albuminuria is the main manifestation of urine routine of myeloma renal damage, while cylindruria is not often seen. So plasma cell (tumor cell) may be observed in examination of urine sediment dyeing. What has diagnosis significance is that Bence Joins protein appears in urine. Detection rate of immunoglobulin (lg) in MM urine is very Io, which shows that light chain has not relation with lg. After condensation an dilution, the urine still shows a positive light chain. Light chains of renal disease and other multiple clonal lg histiocytosis have no concentration and dissolvng characteristics, and their protein electrophoresis s usually 2 or 3 strips, even 5. Globulin belt at the center is thick, and fades to the two sides, even not obvious at the edges. These phenomenon stated above show the inhomogeneity of light chain urine molecules. ②A few patients may not have abnormae urine routine, but only increase of BUN and Scr. ③Speed of ESR increases obviousey, usually being faster than loom/1h;④imbalance between anemia degree and renal failure degree, and the former usually less serious than the latte(5)⑤ It is not usually seen that kidney volume shrinks when renal faiiure occurs, which may be related to renal amyloidosis; ⑥Characteristic of MM chronic renal failure is that there is usually not high blood pressure(6-9)
In one word, renal failure is usually caused by MM. Clinicians are recommended to carry out marrow cell morphoiogicae examination to every patient with renal failure, especially with clinicai manifestation of MM. Because renal damage is a commonly-seen complication of MM.
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