Impaired kidney function is a dangerous complication of multiple myeloma. It is found in half of all patients at the time of diagnosis and ranks second after infections among the causes of death. According to a study conducted by the Medical Research Council, renal function is the most important single factor determining the prognosis of this disease; it was shown that mortality among patients with a blood urea level of more than 12 mmol/l was 5 times higher than among patients with a normal value of this indicator at the time of diagnosis. Renal dysfunction in myeloma may be based on many different mechanisms, leading to acute or chronic renal failure, nephrotic syndrome (usually in combination with amyloidosis) or, rarely, Fanconi syndrome. Of particular importance in the pathogenesis of kidney damage is given to easily remediable disorders, such as hypercalcemia, hyperuricemia and increased blood viscosity. An increase in serum calcium or uric acid levels can undoubtedly be associated with acute renal failure, and vomiting and polyuria accompanying hypercalcemia increase the loss of water due to a direct violation of its tubular reabsorption. Due to dehydration and associated blood hypertonicity, the administration of a contrast agent for intravenous urography to such patients is contraindicated.

The cause of progressive chronic renal failure, so often observed in multiple myeloma, remains controversial. A clear association between renal dysfunction and urinary excretion of paraprotein light chains has been reported, but this observation has not been confirmed by all investigators. Of the 35 patients examined, all 9 without Bence Jones proteinuria had creatinine clearance (CCR) above 50 ml/min.

In more than half of the patients with Bence Jones proteinuria, CCR was below 50 ml/min. The severity of light chain excretion correlated with the degree of renal failure. Most patients with daily Bence Jones protein excretion above 1 g had severe renal failure(average Ccr value was 8 ml/min). A similar relationship was found in the Medical Research Council's First Study.

The assumption of blockage of the tubules as a result of deposits of Bence-Jones paraprotein currently appears doubtful, since in some patients with very high levels excretion of light chains, renal function remains normal. In addition, histological studies of renal biopsy specimens showed that in the presence of casts, the latter consist of albumin, immunoglobulin and a mixture of light chains x and X and that severe renal dysfunction can occur in the absence of tubular casts. Severe tubular atrophy is a pathomorphological sign that most closely correlates with the clinical manifestations of “myeloma kidney”. Light chains are metabolized in tubular cells, causing a direct toxic effect on them.

The urine pH may shift toward the alkaline side, and the concentrating ability of the kidneys may also be impaired. Rarely, Fanconi syndrome occurs in multiple myeloma. In all these cases, the patient had Bence Jones proteinuria, and the diagnosis of multiple myeloma was sometimes preceded by proximal tubular dysfunction for a number of years.

One study found renal amyloidosis in 7% of cases, which could well be the cause of nephrotic syndrome or renal failure. Infection urinary tract Rarely is the primary cause of renal failure, but aggravates existing kidney damage.

What is Kidney Damage in Myeloma?

Kidney damage is regarded as the most common clinical, morphological and laboratory (biochemical) manifestation of myeloma and at the same time one of the most severe and unfavorable prognostic complications of this disease. The incidence 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 serve as the first, earliest clinical and laboratory manifestations of myeloma, which served as the basis for identifying the renal form of this disease. Kidney damage caused by multiple myeloma is referred to as “myeloma nephropathy” or “myeloma kidney”, less often 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 to myeloma and are caused by para- and disproteinosis. The term “myeloma kidney” corresponds to this nature of kidney damage. In other cases of myeloma nephropathy, changes in the kidneys are nonspecific (or not strictly specific) for this disease and manifest themselves in the form of pyelonephritis, renal amyloidosis, nephrocalcinosis, arteriolosclerosis.

Relatively frequent pyelonephritis and arteriolosclerosis of the kidneys are explained by the predominance of elderly people among patients with multiple myeloma and a decrease in the body's resistance to infection in this disease.

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 essence of myeloma itself, to remind the reader of the main symptoms of this disease and the criteria for its diagnosis.

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

What causes kidney damage in multiple myeloma?

The etiology of multiple myeloma is still unclear. Its characteristic feature is the ability of myeloma cells to produce pathological proteins - paraproteins. Therefore, multiple myeloma is also referred to as “paraproteinosis.”

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

Symptoms of kidney damage in multiple myeloma

The clinical picture of multiple myeloma is caused by damage to the bone and hematopoietic systems, metabolic disorders (mainly protein and mineral) and visceral pathology.

First clinical symptoms myeloma, which are found in more than 50% of patients, are such general symptoms, such as weakness, decreased performance and appetite, asthenia, weight loss and bone pain. Often the disease begins sudden pain in the bones or even a spontaneous fracture of one of the bones. In some cases, patients seek medical assistance with 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 specifically for bone pain (ossalgia). Their occurrence 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 bones, as well as the proximal parts of the tubular bones (shoulder, femur). In a later stage of the disease, visible deformation appears, and then spontaneous fractures, which are observed in 50-60% of patients; Fractures of the ribs, vertebrae and hips are especially common. In this case, the vertebral bodies become flattened and deformed (compression fracture), taking on the shape of “fish vertebrae” and accompanied by a shortening of the patient’s height. Tumors (myelomas) arising from flat bones are usually multiple, sometimes reaching large sizes; occur in approximately 15-20% of cases.

X-rays reveal round-shaped bone tissue defects with a diameter ranging from a few millimeters to 2-3 cm or more, which in the bones of the skull appear to be “moth-eaten” or “knocked out with a punch,” 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”.

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

cytosis (mainly in the initial stage of the disease); thrombocytopenia is not typical for myeloma. The number of reticulocytes, as a rule, does not increase. Possible development 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 reveals in the vast majority of patients (90-95%) a clear myeloma cell proliferation with the presence of tumor (myeloma) cells of more than 15%. Bone marrow puncture examination is decisive diagnostic value.

The syndrome of protein pathology in myeloma is most clearly manifested in the form of hyper- and paraproteinemia (or pathoproteinemia). These disorders of protein metabolism are associated with excessive production by pathologically altered plasma (myeloma) cells of abnormal proteins - patho(or para) proteins from the group of immunoglobulins, which, however, although related (similar), are not identical to the corresponding normal fraction of IgM, IgG and IgA . This is the fundamental difference between myeloma paraproteinemia and dysproteinemia of other origins (for example, in rheumatoid arthritis, liver cirrhosis, etc.), characterized by hypergammaglobulinemia. Consequently, it is not the quantitative ratios of the globulin fractions of the electropherogram that have diagnostic significance in myeloma, but their qualitative features. As for the content of ordinary γ-globulins in the blood serum during myeloma, it is not only not increased, but, on the contrary, is always significantly reduced, i.e., there is constant hypogammaglobulinemia. Using protein electrophoresis, paraproteinemia is detected in 90-92% of cases. In this case, the most important and specific criterion for myeloma paraproteinemia is the presence on the proteinogram of a narrow intense M band either between the y-, b-fractions, or in the area of ​​the y-, b- and less often the a-2-globulin fraction.

For myeloma paraproteinemia, a very characteristic and pathognomonic sign is also the presence of low molecular weight Bence-Jones protein (with a molecular weight of 40,000) in the urine. This protein is synthesized only by myeloma cells. Entering the bloodstream due to its small size, it is quickly excreted by the kidneys and appears in the urine. Like creatine, almost complete purification of this protein from the blood occurs in the kidneys. Therefore, it can be detected in the blood only in minimal quantities and only with the help of immunoelectrophoresis. Freely penetrating through the glomerular filter, Bence-Jones protein gives a picture of isolated proteinuria typical of multiple myeloma. Detection of this protein using electrophoresis is of extremely important diagnostic value, allowing diagnosis at an early stage, even before pronounced clinical signs, which is especially important in elderly people with proteinuria unknown origin. Only at the late stage of myeloma is a significant amount of other (serum) proteins detected in the urine, which neutralize the electrophoretic picture characteristic of Bence-Jones proteinuria.

Hyperproteinemia (over 80-90 g/l) in multiple 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 in myeloma most often manifests itself as damage to the kidneys and much less often - to 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.

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As for the pathogenesis of myeloma nephropathy, it consists primarily in damage to the renal nephrons by pathological

(abnormal) proteins - paraproteins. Taking this into account, myeloma nephropathy in its origin is considered a classic example of “excretion nephrosis” (G. A. Alekseev, 1970). Specific to a true myeloma kidney is the deposition of precipitates of pathological myeloma proteins in the distal parts of the tubules with blockage and damage to the latter. At the same time, micromolecular Bence Jones proteins synthesized by myeloma cells enter the bloodstream, reach the kidneys and easily pass through the intact glomerular filter. In the lumen of the tubules, where the fluid has an acidic reaction, the protein masses filtered in the glomeruli coagulate, forming a large number of cylinders leading to obstruction of the lumen of the distal tubules. As a result, the intratubular pressure in the overlying (proximal) sections of the tubules increases with the expansion of their lumen and the development of so-called intrarenal hydronephrosis (nephrohidrosis). In addition, pathological proteins partially reabsorbed by the tubular epithelium penetrate into the interstitial tissue, causing swelling of the renal stroma, stagnation of lymph with the occurrence of lymphocytic infiltrates, i.e., an inflammatory process in the interstitial tissue (interstitial nephritis). Subsequently, hyalinosis and sclerosis of the interstitium develop, followed by death of glomeruli, nephrons and nephrotic shrinkage of the kidneys. Damage to the tubules can cause the development of nephrotic syndrome.

All other lesions of the nights found in myeloma are nonspecific. So, as a result of infection, pyelonephritis can occur. Approximately 5-25% of patients develop renal amyloidosis. Metabolic disorders often lead to the development of not only interstitial nephritis, but also nephrocalcinosis and urolithiasis.

Pathogenesis (what happens?) during myeloma nephropathy:

Macroscopically, the kidneys with myeloma nephropathy are enlarged in size, dense in consistency, and intensely red in color. On the incision, the edematous medulla bulges. In some cases, the kidneys may be reduced in size and wrinkled.

Histologically, the main changes are found in the distal tubules. Most characteristic of a myeloma kidney is the abundance of cylinders in the dilated lumens of the tubules, in some areas with calcium deposits (calcareous cylinders). The appearance of these cylinders is associated with the precipitation of Bence Jones protein. In some cases, most of the tubules are filled with homogeneous protein masses. Sometimes cylinders of a characteristic scaly shape are surrounded along the periphery by giant cells such as resorption cells foreign bodies. The epithelium of the tubules undergoes significant changes in the form of hyaline-vacuolar, vacuolar and granular dystrophy, and is easily desquamated. These epithelial changes develop predominantly in the proximal tubules, where Bence Jones protein is reabsorbed, which is believed to have a direct damaging effect on epithelial cells. In some cases, deposits of paraproteins are found in the glomeruli, interstitial tissue and around the vessels.

However, it should be noted that the renal glomeruli in myeloma nephropathy almost do not undergo pathological changes, with the exception of those cases that are accompanied by the development of amyloidosis. In the interstitial tissue, areas of fibrosis and cellular infiltrates are detected (in at least 50% of cases). The vessels of the kidneys, like the glomeruli, remain practically intact in a true myeloma kidney. With severe and prolonged hypercalcemia, nephrocalcinosis and stone formation develop (in approximately 10% of cases). Since multiple myeloma develops predominantly in older people, atherosclerosis of the renal vessels is often detected and the possibility of developing renal ischemia is associated with this. Subsequent disorders of lymph and blood circulation lead to the death of nephrons and the development of nephrosclerosis with the clinical picture of chronic renal failure. It should be noted that in some patients, regardless of the severity of the clinical and laboratory manifestations of myeloma nephropathy, no significant changes are found in the kidneys.

Symptoms of myeloma nephropathy:

The clinical picture of myeloma nephropathy is characterized by significant diversity. This depends both on the nature of the pathological changes in the kidneys and on the symptoms of damage to other organs and systems, mainly the skeletal system. The earliest and most persistent sign of myeloma is proteinuria, which is found in 65-100% of patients. Its severity varies widely - from traces of protein to 3.3-10 g/l, and sometimes it reaches 33 g/l and even 66 g/l. There are cases where persistent, persistent proteinuria was the only symptom of multiple myeloma for many years. Sometimes proteinuria can long precede the appearance of other symptoms of this disease. In such cases, the disease lasts for a long time under the mask. chronic glomerulonephritis with isolated urinary syndrome. Using electrophoresis of urine proteins (from its daily volume) on paper or in starch gel, as well as immunoelectrophoresis, it is possible to establish the micromolecular (Bence-Jones protein) nature of the myeloma uroprotein in the form of a monoclonal peak (“M” gradient), similar to a similar peak in the electropherogram serum proteins. Bence-Jones uroprotein is electrophoretically detected in the urine of 95% of patients with multiple myeloma (G. A. Alekseev, 1970). Therefore, in every case of proteinuria of unknown etiology, especially in the elderly, as a rule, it is necessary to carry out electrophoresis of urine proteins, i.e., examine the uroproteinogram. The uroproteinogram of patients with myeloma nephropathy, in contrast to proteinuria of other origins, is characterized by a predominance of globulins over albumins with the presence of a “globulinuria peak”. Considering the above, the qualitative characterization of urine proteins using the mentioned methods has exclusively diagnostic significance.

Myeloma nephropathy is characterized by the presence of Bence Jones protein in the urine. However, in a routine study by heating urine to 50-60 °C, Bence Jones protein is detected in only 30-40% of patients. Meanwhile, its presence has not only diagnostic but also prognostic significance, since the persistent presence of this protein in the urine may indicate the imminent development of irreversible renal failure. Bence Jones protein makes up the bulk of urine proteins and its daily excretion can reach 20 g or more (I. E. Tareeva, N. A. Mukhin, 1986). In the urine sediment, hyaline casts are constantly found, less often - granular and epithelial, and in the case of pyelonephritis, leukocyturia is detected. Hematuria is not typical for myeloma kidney, and only in rare cases is there slight erythrocyturia (3-10 red blood cells per field of view). Approximately 1/3 of patients have phosphaturia and alkaline urine reaction.

Edema, arterial hypertension and changes in the vessels of the fundus are not characteristic of myeloma nephropathy and are usually absent, even with the development of renal failure. Arterial pressure, as a rule, does not increase and tends to decrease as the disease progresses. Edema is possible only in those rare cases when myeloma nephropathy manifests itself in the form of renal amyloidosis with nephrotic syndrome.

Clinically, myeloma nephropathy occurs in the form of a kind of “nephrosis of excretion” with relatively quickly (subacutely) developing renal failure, which is manifested by polyuria, decreased glomerular filtration, hyperazotemia, ending in death due to azotemic uremia. Renal failure in myeloma occurs in 20-40% of patients and is regarded as the second most common cause of death in these patients (after infectious complications). The development of renal failure is usually preceded by more or less prolonged proteinuria with the presence of Bence Jones protein in approximately 1/3 of patients. It is interesting to note that in the absence of this protein in the urine, renal failure does not develop even with severe and prolonged proteinuria. In the mechanism of development of renal failure, in addition to Bence-Jones protein, which has a nephrotoxic effect on the tubular epithelium, obstruction of the lumen of the tubules (tubular obstruction), as well as factors such as hypercalcemia, hyperuricemia, increased viscosity of blood plasma, nephrocalcinosis and the development of in some cases of plasmacytic infiltrates.

Proteinuria and chronic renal failure are the most common and characteristic manifestations of myeloma nephropathy. Other renal syndromes and symptoms are less common (acute renal failure, nephrotic syndrome, Fanconi syndrome).

In some cases, acute renal failure may develop as an initial manifestation of myeloma nephropathy. The reasons for its occurrence are various: most often as a result of blocking the tubules with protein precipitates or calcium crystallization (nephrocalcinosis). For example, cases of the development of acute renal failure in patients with multiple myeloma have been described immediately after intravenous (excretory) urography, which was performed to clarify the cause of proteinuria of unknown origin. ARF in such cases is very difficult and usually ends in death. Therefore, if multiple myeloma is suspected, and even more so if the diagnosis of this disease has already been established, excretory urography is contraindicated for such patients.

Nephrotic syndrome, as already noted, is rare in myeloma and is usually the result of the addition of amyloidosis.

In some cases, when myeloma nephropathy occurs with severe damage to the tubules, pronounced dysfunction of the latter develops with a violation of their partial functions. As a result, glucosuria, aminoaciduria, phosphaturia, hypokalemia and hyposthenuria may appear, i.e., signs characteristic of Fanconi syndrome, which often complicates the course of myeloma.

The treatment of myeloma nephropathy, like myeloma itself, is chronic, steadily progressing, with the development of chronic renal failure, which in approximately 1/3 of cases is the direct cause of death. In diffuse forms of myeloma with total damage to the bone marrow, the cause of death is severe anemia and hemorrhagic diathesis. In other cases, death occurs due to symptoms of general cachexia or as a result of complications associated with multiple bone fractures - pneumonia due to rib fractures, urosepsis due to compression fractures of the vertebrae.

The average duration of the disease from the onset of its first clinical and laboratory manifestations is 2-5 years and only in some uncomplicated cases reaches 6-10 years (G. A. Alekseev, 1970).

Diagnosis of myeloma nephropathy:

It is very difficult to make a diagnosis of myeloma nephropathy, especially in cases where it is the first or main syndrome of myeloma. Kidney damage, accompanied by isolated and persistent proteinuria, often occurs under the guise of glomerulonephritis, amyloidosis or pyelonephritis. Lifetime clinical diagnosis diagnosis of such variants of multiple myeloma is very difficult, and diagnostic errors reach 30-50% (A.P. Peleshchuk, 1983). The presence of anemia and an increase in ESR initially do not find a proper explanation, and only in the late stage of the disease are they retrospectively given a correct assessment.

It is also necessary to think about the possibility of a myeloma kidney in cases where proteinuria appears “for no reason” (without a previous sore throat, in the absence of a history of indications of acute glomerulonephritis, chronic suppurative diseases, etc.) in combination with anemia, high ESR, especially if this combination is observed in persons over 40-45 years of age, in the absence of edema, arterial hypertension, hematuria and in the presence of hyperproteinemia and hypercalcemia. The diagnosis is more convincing if the mentioned signs develop against the background of bone pathology, i.e. against the background of bone pain.

To clarify the diagnosis, it is necessary to examine the urine for Bence-Jones protein, conduct x-rays of bones (skull, ribs, ilium, vertebrae), electrophoresis of blood and urine proteins (in order to detect the “M”-fraction or “M”-gradient specific to myeloma) and finally sternal puncture. As for puncture biopsy of the kidney, the diagnostic value of this method is controversial, since morphological changes in the kidneys in myeloma are characterized by great diversity, and it is not always possible to establish specific signs of myeloma. At the same time, a puncture biopsy of the kidney can exclude amyloidosis and glomerulonephritis.

Chronic renal failure caused by myeloma, unlike chronic renal failure of other etiologies (in particular, glomerulonephritis), is not accompanied by the development of arterial hypertension and hypocalcemia. The level of calcium in the blood of such patients is always elevated, including in the stage of chronic renal failure. With the development of tubular acidosis in the blood, the level of sodium and chlorine increases and the potassium content decreases, while in the urine the daily excretion of sodium, chlorine, calcium, phosphorus decreases and the excretion of potassium increases.

Treatment of myeloma nephropathy:

To date, there are no reliable methods. treatments for myeloma. However, the use of complex therapy using cytostatics (sarcolysin, cyclophosphamide, etc.) in combination with glucocorticoids and anabolic hormones allows in many cases to achieve long-term (up to 2-4 years) clinical remission and, consequently, an increase in the patient’s life expectancy and temporary recovery his physical activity and even ability to work (for persons not engaged in physical labor).

However, cytostatics and glucocorticoids can be prescribed only in the absence of signs of renal failure. In patients with myeloma nephropathy in the stage of chronic renal failure, the use of these drugs is contraindicated. In such cases, symptomatic therapy is carried out (as with chronic renal failure of other etiologies). Peritoneal dialysis and hemodialysis are not recommended. In some cases, plasmapheresis is used. Kidney transplantation is not indicated for such patients.

To correct the hypercalcemia observed in myeloma kidney, corticosteroids, diuretics, and calcitonin are prescribed; Plenty of fluid intake is recommended (to combat dehydration and increase diuresis). With the development of hyperuricemia, allopurinol is indicated. The introduction of detoxification solutions, blood and red blood cell transfusions are also used.

Which doctors should you contact if you have myeloma nephropathy:

Nephrologist

Hematologist

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Other diseases from the group Diseases of the genitourinary system:

"Acute abdomen" in gynecology

Algodismenorrhea (dysmenorrhea)

Algodismenorrhea secondary

Amenorrhea

Amenorrhea of ​​pituitary origin

Kidney amyloidosis

Ovarian apoplexy

Bacterial vaginosis

Infertility

Vaginal candidiasis

Ectopic pregnancy

Intrauterine septum

Intrauterine synechiae (fusions)

Inflammatory diseases of the genital organs in women

Secondary renal amyloidosis

Secondary acute pyelonephritis

Genital fistulas

Genital herpes

Genital tuberculosis

Hepatorenal syndrome

Germ cell tumors

Hyperplastic processes of the endometrium

Gonorrhea

Diabetic glomerulosclerosis

Dysfunctional uterine bleeding

Dysfunctional uterine bleeding of the perimenopausal period

Cervical diseases

Delayed puberty in girls

Foreign bodies in the uterus

Interstitial nephritis

Vaginal candidiasis

Corpus luteum cyst

Intestinal-genital fistulas of inflammatory origin

Colpitis

Uterine fibroids

Genitourinary fistulas

Disorders of sexual development in girls

Hereditary nephropathies

Urinary incontinence in women

Necrosis of myomatous node

Incorrect positions of the genitals

Nephrocalcinosis

Nephropathy in pregnancy

Nephrotic syndrome

Nephrotic syndrome primary and secondary

Acute urological diseases

Oliguria and anuria

Tumor-like formations of the uterine appendages

Tumors and tumor-like formations of the ovaries

Sex cord stromal tumors (hormonally active)

Prolapse and prolapse of the uterus and vagina

Acute renal failure

Acute glomerulonephritis

Acute glomerulonephritis (AGN)

Acute diffuse glomerulonephritis

PLAN

I.Introduction

II. Multiple myeloma and myeloma nephropathy

Etiology

Classification Pathogenesis

Morphological changes

Clinical manifestations

Diagnostics

III. Bibliography

I.INTRODUCTION

Kidney damage is regarded as the most common clinical, morphological and laboratory (biochemical) manifestation of myeloma and at the same time one of the most severe and unfavorable prognostic complications of this disease. The incidence of kidney damage in myeloma ranges from 60 to 90 and even up to 100%. In many cases, pathological changes in the kidneys serve as the first, earliest clinical and laboratory manifestations of myeloma, which served as the basis for identifying the renal form of this disease. Kidney damage caused by multiple myeloma is referred to as “myeloma nephropathy” or “myeloma kidney”, less often as “paraproteinemic nephrosis”. Pathological changes in the kidneys can be of a different nature and differ in significant polymorphism. In some cases, they are strictly specific to myeloma and are caused by para- and disproteinosis. The term “myeloma kidney” corresponds to this nature of kidney damage. In other cases of myeloma nephropathy, changes in the kidneys are nonspecific (or not strictly specific) for this disease and manifest themselves in the form of pyelonephritis, renal amyloidosis, nephrocalcinosis, arteriolosclerosis.

Relatively frequent pyelonephritis and arteriolosclerosis of the kidneys are explained by the predominance of elderly people among patients with multiple myeloma and a decrease in the body's resistance to infection in this disease.

II. MYELOMA DISEASE AND MYELOMA NEPHROPATHY

Myeloma, or plasmacytoma, is a group of tumor processes in the B-lymphocyte system related to paraproteinemic hemoblastoses, diseases of the immunocompetent system, manifested by overproduction of homogeneous (monoclonal) immunoglobulins or their fragments.

Etiology multiple myeloma has not yet been clarified. Its characteristic feature is the ability of myeloma cells to produce pathological proteins - paraproteins. Therefore, multiple myeloma is also referred to as “paraproteinosis.”

A feature of this group of diseases is the homogeneity of the tumor mass, originating from one single cell, which determines the production of certain immunoglobulins. Pathological production of one type of immunoglobulin, two (IgG, IgA) coming from plasma cells, or IgM from lymphoid cells is possible. Production of macroglobulin (protein-M) is possible. When a clone of cells producing immunoglobulin heavy chains grows, heavy chain disease develops.

In 1846, D. Dalrymple described softening and fractures of bones found at autopsy. It took 40 years for a completely modern doctrine of multiple myeloma to emerge. Discovered by Henry Bence-Jones (1847, 1848) and later by McIntyre (1850) a special type of protein in urine, according to modern ideas classified as a light chain polypeptide, opened the way to massive study of this disease. In 1873, Rustitsky described “multiple myeloma,” and O. Kaler (1889) described its full clinical picture, including myeloma nephropathy. The structure of the latter was illuminated in detail only in 1920 by S. Thanhauser and E. Kraus.

The disease occurs more often between the ages of 40 and 70 years. Its frequency is 1:100,000 population per year.

Myeloma nephropathy (MN) is a formidable manifestation of multiple myeloma; it occurs, according to various authors, from 30 to 50% and even up to 80%.

All myeloma cells develop from a single progenitor cell. The reasons leading to the emergence of a clone of myeloma cells have not yet been established. Most researchers associate its appearance with the activation (expression) of certain oncogenes. The expression of oncogenes can be caused by both point mutations of oncogenes that occur as a result of various influences, and various kinds of translocations within one or several chromosomes. Apparently, as a result of these changes, the genes begin to encode the synthesis of altered (tumor) messenger RNA and the cell acquires all the characteristics of a malignant one. Tumor plasma cells are stimulated by various growth factors, mainly interleukin-6, but also possibly granulomonocyte colony-stimulating factor, interleukin-3, which are produced by bone marrow monocytes, macrophages, T cells (paracrine stimulation), or the myeloma cells themselves (autocrine stimulation). It is significant that in myeloma, unlike many other blood diseases, no specific chromosomal changes have been identified.

The process is based on diffuse or focal proliferation of pathological plasma cells that produce paraproteins. Proliferation of plasma cells in bone marrow leads in most cases to the destruction of bone substance, since myeloma cells produce osteoclastizing factor. Flat bones, vertebrae, and proximal sections of tubular bones are primarily affected by destruction.

Numerous classifications of myeloma, distinguishing with various variations multinodular, diffuse, diffuse nodular, bone, extraosseous and other forms, according to many, may rather be stages of the disease. Kidney lesions in myeloma are also considered differently depending on the morphological or clinical approach.

Classification. Taking into account the complex relationships that develop in the patient’s body, caused by the action of a number of etiological, as well as accompanying factors, metabolic disorders, it is advisable to consider variants of MN, according to the scheme of L. Morel-Marodger (1979):

1) kidney damage directly associated with myeloma (Bence-Jones proteinuria, renal acidosis, Fanconi syndrome with tubular degeneration, salt-wasting nephritis, renal failure, formation of tubular casts, interstitial plasmacytic infiltration, amyloidosis, glomerulosclerosis);

2) metabolic disorders (hypercalcemia, hyperuricemia, dehydration);

3) acute renal failure (due to intravenous urography).

4) infectious complications (pyelonephritis, interstitial nephritis).

Pathogenesis. From the above classification it is clear that the nature of the involvement of the kidneys in pathological process is heterogeneous and therefore the mechanisms of kidney damage should be considered separately, taking into account the direct and indirect influence of dysproteinemia. Changes in the kidneys directly related to the formation of myeloma are caused by the effect of paraproteins on the renal tissue.

The kidneys do not play any significant role in the metabolism of whole immunoglobulins. Intact immunoglobulin molecules do not pass through the normal glomerular filter and are not reabsorbed in the tubules.

Glomerular filtration of these molecules can only occur if the capillary wall is damaged, however, even in this case, reabsorption of immunoglobulins will not occur, and they will end up in the urine without being catabolized when moving through the tubules. Thus, the presence of intact immunoglobulins in the urine is an indicator of glomerular damage.

Myeloma nephropathy is a disease that consists primarily of damage to the renal nephrons by abnormal proteins - paraproteins. A characteristic feature of a true myeloma kidney is the deposition of precipitates of abnormal myeloma proteins in the distal parts of the tubules with damage and blockage of the latter. Kidneys with myeloma nephropathy are enlarged in size, have a dense consistency, and an intense red color. The edematous medulla swells on the incision. In some cases, the kidneys are wrinkled and reduced in size. Most typical for a myeloma kidney is an abundance of cylinders in the dilated lumens of the tubules, in some areas with calcium deposits (calcareous cylinders). In some cases, most of the tubules are flooded with homogeneous protein masses. Sometimes cylinders of a specific scaly shape are cordoned off along the periphery by giant cells, like foreign body resorption cells. The epithelium of the tubules is subject to significant transformations in the form of vacuole, hyaline-vacuole and granular dystrophy, and is freely desquamated. In the interstitial tissue, areas of cellular infiltrates and fibrosis are found (in no less than 50% of cases). With true myeloma, the renal vessels, like the glomeruli, remain almost intact. With severe and prolonged hypercalcemia, nephrocalcinosis and stone formation begin (in almost 10% of cases). Since multiple myeloma develops mainly in elderly people, the phenomena of atherosclerosis of the renal vessels are often detected and the possibility of developing renal ischemia is combined with this.

treatment

To date, there are no reliable methods and remedies for the treatment of multiple myeloma. Nevertheless, the use of complex therapy using cytostatics (cyclophosphamide, sarcolysine, etc.) in combination with glucocorticoids and anabolic hormones allows in many cases to achieve long-term (up to 2-4 years) clinical remission and, thus, increase the patient’s life expectancy.

symptoms

The earliest and most persistent sign of myeloma is proteinuria, which is found in 65-100% of patients. The symptoms of myeloma nephropathy lack the usual HC variant: hypoproteinemia, edema, hypercholesterolemia; do not note symptoms of vascular lesions of the kidney - retinopathy, hypertension. Hyper- and dysproteinemia with a predominant content of beta-globulins and abnormal paraprotein are characteristic. Various types of cylinders are found in urine sediment, mostly giant cylinders with a layered structure. Leukocyturia and erythrocyturia are often absent. Some patients (23%) experience symptoms of acute nephronecrosis, which leads to acute renal failure with oligo- or anuria and a constant increase in azotemia.