Subacute Glomerulonephritis

What is Subacute Glomerulonephritis?

This is a special form of glomerulonephritis, which is characterized by a peculiarity of morphological changes in the kidneys, severe clinical manifestations, a rapidly progressing course, early onset and rapidly increasing renal failure, ending with an unfavorable outcome in a short period of time – from 2-3 weeks to 6-12 months. The disease was first described in 1914 by F. Folhard and T. Far, who considered it as a subacute form of glomerulonephritis and proposed the term “extracapillary nephritis” for it.

Previously, this disease was described by various authors as a special variant of acute or chronic glomerulonephritis. So, Ellis (1942) attributed it to one of the variants of the course of acute glomerulonephritis. However, due to the characteristic features of the histomorphological picture and clinical manifestations, it is isolated in a separate nosological form, which in clinical practice is most often referred to as subacute malignant glomerulonephritis. The term “extracapillary nephritis” reflects only its morphological essence. Other terms used in the literature to refer to this disease – “rapidly progressive”, “transient”, “super acute”, “anuric”, “stormy”, “endoextracapillary”, glomerulonephritis – reflect its morphological and clinical nature to a lesser extent, therefore, they do not find wide clinical applications. However, some authors (E. M. Tareev, 1983; B. I. Shulutko, 1983; N. A. Mukhin, I. E. Tareeva, 1992 and others) describe it as rapidly progressive glomerulonephritis.

Subacute (malignant) glomerulonephritis is a relatively rare kidney disease. Among all forms of glomerulonephritis, it accounts for 1-4% (G. Majdrakov, 1980; S.I. Ryabov, 1980, 1982; E.M. Tareev, 1983). Malignant glomerulonephritis occurs with almost the same frequency in people of both sexes, mainly after 40 years. L. A. Pyrig (1982), on the basis of his own observations and generalizations of the literature, established that subacute malignant glomerulonephritis after the age of 40 occurs 3-4 times more often than in younger people. According to the materials of S. I. Ryabov (1980), among the patients observed by him with subacute malignant glomerulonephritis at the age of 13-83 years, 57.4% were people over 40 years old. At the same time, according to other authors (A. Pukhlev, 1980), this disease occurs more often at the age of 15-30 years.

Causes of Subacute Glomerinephritis

Since this disease in some cases occurs after a streptococcal infection, an opinion is expressed about the possibility of its infectious etiology (E. M. Tareev, 1972; A. P. Peleschuk, 1974). However, a similar relationship between the onset of subacute malignant glomerulonephritis and streptococcal infection is relatively rare. In some cases, this disease may be a consequence of hemorrhagic vasculitis, viral infections, bacterial endocarditis, SLE, periarteritis nodosa, Goodpasture, Wegener syndromes, malignant neoplasms, abscesses of various localization, exposure to drugs, chemicals and other reasons. Therefore, subacute (malignant) glomerulonephritis is a polyetiological disease, which has given some authors the basis to designate it as a syndrome. However, in many cases, the cause cannot be determined (idiopathic malignant nephritis).

Pathogenesis during Subacute Glomerulonephritis

According to modern concepts, the disease is an immuno-inflammatory genesis. Two types of subacute glomerulonephritis are distinguished. The first is regarded as a malignant variant of acute post-streptococcal glomerulonephritis, the second as an autoimmune disease. The first type is based on the immunocomplex development mechanism with the deposition of immune complexes (antigen – antibody) in the wall of the glomerular capillaries of the kidneys. In the second, autoimmune, antibodies are formed to the basement membrane of the glomerular capillaries (A.P. Peleschuk, 1983).

The pathomorphological picture of subacute malignant glomerulonephritis is fairly well understood, both from autopsy and from intravital puncture kidney biopsy. Macroscopically, the kidneys are normal or enlarged. The surface is smooth, the fibrous capsule is easily removed, the parenchyma is flabby, yellowish-white or grayish-yellow. In the section, the cortical substance is wide with yellowish spots and stripes (due to deposition of lipids). This usually enlarged kidney is called a “large white kidney.” Sometimes, against the background of the grayish-yellow surface of the cortical substance, numerous point and spotted hemorrhages are visible in the form of red specks. Such a kidney is called a “large motley kidney.”

For subacute malignant glomerulonephritis, the most typical histological changes are the presence of half moon, which in typical cases of this disease is found in at least 80% of the glomeruli. They are formed due to pronounced proliferation of the epithelium of the parietal and visceral leaves of the Shumlyansky-Bowman capsule. Accumulating in the cavity of the capsule and filling all or almost its entire lumen, the epithelial cells push the glomerular capillary loops to the vascular pole and squeeze them. In this case, the glomerular cavity takes the form of half moon, which are sometimes detected already a week later from the onset of the disease.

Fibrin falls into the cavity of the glomerular capsule, resulting in fibroplastic and fibrotic changes in the glomeruli. Due to the compression of the glomerular capillaries by the formed semilunas, their ischemia occurs, thrombosis and necrosis of the capillary wall occur. Along with the rapid proliferation of epithelial cells, pronounced proliferation of the glomerular capillary endothelium is observed, which leads to obstruction of their lumen, contributes to glomerular ischemia, and the development of thrombosis. As a result, glomerular hyalinosis rapidly develops, followed by their fibrosis and death. Deep changes are observed in the tubules. Already in the initial phase of the disease, pronounced dystrophic changes in the convoluted tubule epithelium are detected in the form of protein, granular, hyaline droplet, vacuole and fatty degeneration, focal proliferation. Subsequently, atrophic changes and epithelial necrosis occur rather quickly. In the interstitial tissue, round-cell infiltration and edema are noted.

Symptoms of Subacute Glomerulonephritis

More often, the disease develops 1-3 weeks after a streptococcal infection or hypothermia. In some cases, the cause cannot be determined. Basically, subacute malignant glomerulonephritis, like the classic version of acute glomerulonephritis, begins violently, with pronounced signs of edematous, hypertensive and urinary syndromes.

Along with edema, which often reaches a significant degree and is accompanied by the development of ascites, hydrothorax and hydropericardium, massive proteinuria is observed, exceeding 3.0-3.5 g per day, severe hypo- and dysproteinemia, hyperlipidemia, in particular hypercholesterolemia, i.e. all the signs of nephrotic syndrome are evident. In addition, hematuria is noted, sometimes significant, cylindruria with the appearance in the urine of hyaline, granular and waxy cylinders, which indicates severe damage to the epithelium of not only the proximal, but also the distal tubules. Pathological changes in the urine are usually combined with a sharp decrease in diuresis, and in some cases oliguria is replaced by anuria or the latter is observed from the very beginning of the disease, which makes us think of acute renal failure.

Arterial hypertension often reaches a significant severity – up to 200-240 / 120-130 mm RT. Art. Unlike acute or exacerbation of chronic glomerulonephritis in subacute malignant: glomerulonephritis, clinical and laboratory signs of the disease are not prone to decrease, and even more so to the disappearance. On the contrary, they persist or grow. Hypertension in about 1/3 of cases acquires a malignant course (E. M. Tareev, 1972). As a result, severe changes in the fundus develop with swelling of the optic nerve, retinopathy, often with hemorrhages in the retina and its detachment, thrombosis of the central retinal artery, which leads to a sharp decrease or complete loss of vision. There may be dynamic disturbances in cerebral circulation, strokes and thromboses of cerebral vessels with corresponding clinical signs. High and persistent hypertension is the cause of the development of cardiac (mainly left ventricular) failure, with cardiac asthma and pulmonary edema. These complications of hypertension can be a direct cause of death of the patient.

Severe and progressive disorders in the structure of the glomerular and tubular apparatus of the nephrons lead to a rapid and significant decrease in renal function. Within 1-3 weeks from the onset of the disease, clinical and laboratory signs of renal failure appear and quickly increase. Glomerular filtration and the concentration ability of the tubules with the development of hypo- and isostenuria are significantly reduced. As a result, growing hyperazotemia develops – blood levels of urea, creatinine, and residual nitrogen increase. As a manifestation of renal failure, anemia develops, in some cases significantly pronounced. ESR increases to 30-60 mm / h, moderate leukocytosis (10-15 thousand) is often observed. Possible violations of the electrolyte balance of the body: hypernatremia, hyperkalemia, etc. Metabolic acidosis develops.

The condition of patients progressively worsens. They complain of headache, shortness of breath, pain in the heart, visual impairment, then nausea, vomiting, skin itching, loss of appetite, sleep disturbance, general weakness join. A frequent subjective symptom of the disease is aching pain, sometimes quite pronounced, in the lumbar region. Sick sluggish, inhibited; the skin is pale, the face is puffy; marked swelling of the whole body, limbs. In the terminal stage, hemorrhagic manifestations on the skin and on the part of the gastrointestinal tract are possible. Rapidly increasing renal failure after just a few weeks or months leads to death.

Subacute malignant glomerulonephritis is more severe in older people (after 50 years), which is associated with the possibility of previous diseases of the cardiovascular system.

The onset of subacute glomerulonephritis can manifest itself as acute renal failure. In some cases, it develops in patients with acute glomerulonephritis, which transforms into malignant. You should think about this if, after 2-3 weeks from the onset of acute glomerulonephritis, improvement does not occur, the patient’s condition remains severe, edema, hypertension, proteinuria, hematuria, hypo- and dysproteinemia, hypercholesterolemia persist and even increase, glomerular filtration and relative density of urine decrease , blood levels of urea and creatinine increase.

With subacute (malignant) glomerulonephritis, the prognosis is always unfavorable. Spontaneous or under the influence of treatment recovery is extremely rare.

Treatment of Subacute Glomerulonephritis

In patients with subacute (malignant) glomerulonephritis, treatment is still considered to be practically unsuccessful. Only single, extremely rare cases of spontaneous recovery are described either under the influence of complex therapy, which often leads to short-term remission. The use of immunosuppressants, glucocorticosteroids and anticoagulants in the treatment of this disease has not given encouraging results. True, some authors point to the possibility of a positive effect: on the reduction and even disappearance of edema, lowering blood pressure, reducing urinary syndrome and improving kidney function, and in rare cases, on complete and stable remission of the disease – under the influence of glucocorticosteroid hormones or when combined with immunosuppressants ( azathioprine, imuran, cyclophosphamide, etc.) and anticoagulants. So, N. A. Ratner (1974) describes the case of complete and persistent (observation period 9 years) clinical and laboratory remission in a patient with subacute malignant glomerulonephritis treated with prednisone. Most clinicians believe that treatment with corticosteroids and cytostatics both separately and in combination does not significantly affect the outcome of the disease and its prognosis.

A few clinical observations indicate that the early initiation of complex (four-component) therapy with glucocorticoids, anticoagulants (heparin), antiplatelet agents (chimes, dipyridamole) and cytostatics (azathioprine, cyclophosphamvzd, etc.) may slightly slow the progression of the disease and prolong the life of patients. The effect of this therapy is slightly increased if it is carried out against the background of hemodialysis. A positive effect is noted from the use of “pulse therapy”, plasmapheresis, hemosorption (N. A. Mukhin, I. E. Tareeva, 1992). In general, the effectiveness of various therapies for malignant glomerulonephritis, including hemodialysis and kidney transplantation, is unsatisfactory. Therefore, mainly symptomatic therapy is used.

Patients are prescribed bed rest, a diet with a restriction of salt and liquid, and with the appearance of renal failure, and protein. Food should be predominantly milk-vegetable. To improve the palatability of light-salted food, it is allowed to add seasonings (parsley, dill, vinegar, mustard, etc.) in moderation.

Diuretics, antihypertensives, cardiac products, vitamins C, B, P, ascorutin, antihistamines, calcium gluconate, dicinone, etc. are widely used (see treatment of acute glomerulonephritis).

With severe and prolonged oliguria or anuria, hyperazotemia, hyperkalemia, the patient should be transferred to hemodialysis.