Kidney Damage in Myeloma

What is Kidney Damage in Myeloma?

Kidney damage is regarded as the most frequent clinical, morphological and laboratory (biochemical) manifestation of myeloma and at the same time one of the most severe and prognostically adverse complications of this disease. The frequency of kidney damage in myeloma ranges from 60 to 90 and even up to 100%. In many cases (according to A.P. Peleshchuk, 28%), pathological changes in the kidneys are the first, earliest clinical and laboratory manifestations of myeloma, which served as the basis for isolating the renal form of this disease. Kidney damage due to myeloma is referred to as “myeloma nephropathy” or “myeloma kidney”, less commonly as “paraproteinemic nephrosis” (N. E. Andreeva, 1979). Pathological changes in the kidneys can be of a different nature and differ in significant polymorphism. In some cases, they are strictly specific for myeloma and are caused by para- and dysproteinosis. The term “myeloma kidney” corresponds to this nature of kidney damage. In other cases of myeloma nephropathy, changes in the kidneys are non-specific (or not strictly specific) for this disease and are manifested in the form of pyelonephritis, renal amyloidosis, nephrocalcinosis, arteriolosclerosis.

The relatively frequent pyelonephritis and arteriolosclerosis are explained by the prevalence of elderly people among patients with myeloma disease and a decrease in the body’s resistance to infection.

For a better understanding of the mechanism of development of myeloma nephropathy, its morphological and clinical manifestations, it is advisable, without dwelling in detail on the pathogenetic nature of the myeloma disease itself, remind the reader of the main symptoms of this disease and the criteria for its diagnosis.

Myeloma (myeloma, plasmacytoma). This is a systemic disease of a tumor-hyperplastic type with a predominant lesion of the skeleton bones, characterized by malignant proliferation of cells of a reticuloplasmic nature (G. A. Alekseev, 197O).

Causes of Kidney Damage in Myeloma

The etiology of myeloma is still not clear. Its characteristic feature is the ability of myeloma cells to produce pathological proteins – paraproteins. Therefore, myeloma is also referred to as paraproteinosis.

The disease occurs mainly at the age of 45-65 years and has a tendency to noticeable growth. This is due not only to improved diagnosis, but also to an increase in the proportion of elderly people. Although there are cases of myeloma and: at a younger age. Men and women get sick at about the same frequency.

Symptoms of Kidney Damage in Myeloma

The clinical picture of myeloma is due to damage to the bone and blood-forming systems, metabolic disorders (mainly protein and mineral) and visceral pathology.

The first clinical symptoms of myeloma, which are found in more than 50% of patients, are such general symptoms as weakness, decreased performance and appetite, asthenia, weight loss and bone pain. Often, the disease begins with sudden pain in the bones or even a spontaneous fracture of one of the bones. In some cases, patients seek medical help with an accidentally detected protein in the urine or an increase in ESR.

Pathological changes in the skeletal system are among the most common and characteristic clinical manifestations of myeloma. They are expressed by the classic triad of symptoms: pain, swelling, and fractures. In 75-90% of cases, patients seek medical help precisely for bone pain (ossalgia). Their appearance is associated with destructive changes in the bones due to tumor growth of myeloma tissue. Mostly flat bones are affected – the skull, sternum, ribs, vertebrae, iliac, as well as the proximal sections of the tubular bones (shoulder, thigh). In a later stage of the disease, deformity visible on the eye appears, and then spontaneous fractures, which are observed in 50-60% of patients; fractures of ribs, vertebrae and hips are especially frequent. In this case, the vertebral bodies are flattened, deformed (compression fracture), acquiring the shape of “fish vertebrae” and accompanied by shortening of the patient’s growth. Tumors (myelomas) emanating from flat bones are usually multiple, sometimes reaching large sizes; occur in about 15-20% of cases.

Radiographs show round-shaped bone defects with diameters from a few millimeters to 2–3 cm or more, which appear to be “eaten by moth” or “knocked out by a piercer” in the bones of the skull, creating a characteristic x-ray picture of the so-called “leaky skull”. In the proximal sections of the tubular bones (humerus, femur), bone defects are radiologically detected in the form of “soap bubbles” or “honeycombs”, and pathologically altered vertebrae resemble fish vertebrae.

The picture of peripheral blood in the initial stage of the disease usually does not have significant deviations from the norm. However, as the disease progresses, all patients develop normochromic type anemia, the pathogenesis of which is not entirely clear. The occurrence and increase of anemia is associated with bone marrow replacement with elements of myeloma tissue. The severity and rate of increase of anemia can be different. As the disease progresses, more or less pronounced leukopenia (neutropenia) is noted. Absolute monocytosis is often observed, and in 2-3% of patients – eosinophilia. Some patients have a tendency to hyperthrombotic

cytosis (mainly in the initial stage of the disease); thrombocytopenia is not characteristic of myeloma. The number of reticulocytes, as a rule, does not increase. Perhaps the development of hemorrhagic syndrome, the genesis of which is complex and not entirely clear. A classic sign of myeloma is a pronounced (up to 50-70 mm / h) and stable increase in ESR, which is often detected long before the appearance of bone and other symptoms of this disease.

Analysis of the myelogram obtained by sternal puncture allows us to identify in the vast majority of patients (90-95%) a distinct myeloma-cell proliferation with the presence of tumor (myeloma) cells of more than 15%. The study of bone marrow punctate is of crucial diagnostic value.

The syndrome of protein pathology in myeloma is most pronounced in the form of hyper- and paraproteinemia (or pathoproteinemia). These disorders of protein metabolism are associated with excess production of pathologically altered plasma (myeloma) cells of abnormal proteins – patho (or a pair) of proteins from the group of immunoglobulins, which, however, although they are related (similar), but not identical to the corresponding normal fraction of IgM, IgG and IgA . This is the fundamental difference between myeloma paraproteinemia and dysproteinemia of other origin (for example, with rheumatoid arthritis, liver cirrhosis, etc.), characterized by hypergammaglobulinemia. Therefore, the diagnostic value in myeloma is not the quantitative ratio of globulin fractions of electrophoregrams, but their qualitative features. As for the content of ordinary γ-globulins in blood serum in case of myeloma, it is not only not increased, but, on the contrary, always significantly reduced, that is, there is constant hypogammaglobulinemia. By protein electrophoresis, paraproteinemia is detected in 90-92% of cases. Moreover, the most important and specific criterion for myeloma paraproteinemia is the presence on the proteinogram of a narrow intense band M either between the y-, b-fractions, or in the region of the y-, b- and less often a-2-globulin fraction.

For myeloma paraproteinemia, the presence of low molecular weight Bens-Jones protein (with a molecular weight of 40,000) is also a very characteristic and pathognomonic sign. This protein is synthesized only by myeloma cells. Entering the blood stream due to its small size, it is rapidly excreted by the kidneys and appears in the urine. Like creatinine, almost complete purification of the blood from this protein takes place in the kidneys. Therefore, in the blood it can be detected only in minimal quantities and only with the help of immunoelectrophoresis. Freely penetrating the glomerular filter, the Bens-Jones protein gives a typical picture of isolated proteinuria typical of myeloma. The detection of this protein by electrophoresis is of extremely important diagnostic value, it allows you to diagnose it at an early stage, even before pronounced clinical signs, which is especially important in elderly people with proteinuria of unknown origin. Only at a late stage of myeloma in the urine is a significant amount of other (serum) proteins detected that level the electrophoretic picture characteristic of Bens-Jones proteinuria.

Hyperproteinemia (over 80-90 g / l) with myeloma occurs in 50-85% of cases and sometimes reaches 150-180 g / l. It is caused by hyperglobulinemia, which in combination with hypoalbuminemia leads to a significant decrease in the A / G coefficient (to 0.6-0.2).

Visceral pathology with myeloma is most often manifested by damage to the kidneys and much less often – the liver, spleen and other organs. In 5-17% of patients, hepato- and (or) splenomegaly is detected. Tumor plasma cell infiltrates can be found in all internal organs, but they rarely appear clinically: they are usually found at autopsy.