Symptoms and Pathogenesis during Diabetic Glomerulosclerosis

What is Diabetic Glomerulosclerosis?

Diabetic glomerulosclerosis is one of the most severe and complex forms of diabetic microangiopathy. It is called Kimmelstil-Wilson syndrome, after the names of the authors who first described it in 1936. There are a number of other names for this disease – diabetic kidney, diabetic nephropathy.

A. S. Efimov (1989) considers the term “diabetic nephropathy” more justified, since there is practically no isolated lesion of the glomerular capillaries without involving other vessels and tubules, and using modern examination methods, it is difficult to determine which lesion and which kidney section prevails. Nevertheless, the term “diabetic glomerulosclerosis” is also valid.

The frequency of clinical manifestations of diabetic glomerulosclerosis, according to different authors, ranges from 6 to 64% (Burger, 1970; A. S. Efimov, 1973; A. Astroug, 1976, and others.). Diabetic glomerulosclerosis is more common in women than in men – 30% and 19.5%, respectively (A. S. Efimov, 1973; A. Astroug, 1976).

Most modern researchers note the relationship between the occurrence of glomerulosclerosis and the duration of diabetes. Often it is not isolated, but is combined with microangiopathies of other localizations, for example, retinopathy, recorded in 70-90% of cases.

Pathogenesis during Diabetic Glomerulosclerosis

The origin of diabetic glomerulosclerosis is not fully understood. There are various hypotheses, the authors of which seek to explain the complex mechanisms leading to the development of this disease. Thus, the theory of primary metabolic disorders explains the vascular lesion in diabetes by circulation in the blood at elevated concentrations of many products of impaired protein, lipid and carbohydrate exchanges with damage to the vascular basal membranes, in particular the renal glomeruli of the SV. V. Serov, 1962; V. V. Serov et al., 1981). For example, a violation of protein synthesis and glycoprotein metabolism leads to the formation of paraproteids, which, due to the increased permeability of the basement membranes, accumulate in the glomeruli, where they turn into a hyaline-like substance. However, the metabolic hypothesis of diabetic microangiopathy does not provide a convincing explanation for their development in the pre-diabetes phase, when these metabolic disorders are not yet identified.

The immunological concept of microangiopathy and diabetic glomerulosclerosis, based on the current idea of ​​a genetic predisposition to diabetes, is discussed. There is evidence of a correlation between the concentration of immune complexes circulating in the blood with the frequency and severity of microangiopathy.

The neuroendocrine hypothesis associates the vascular complications of diabetes with an increased activity of glucocorticoids, adenohypophysis and hypothalamus, which leads to an increase in capillary permeability and deposition of peptide molecules into the vascular wall.

The genetic theory is based on the familial susceptibility to diabetes, found in relatives of patients with diabetes. Proponents of this theory allow for the hereditary transmission of vascular and metabolic disorders in diabetes, changes in carbohydrate tolerance.

Thus, there is no unified theory of the pathogenesis of diabetic glomerulosclerosis. Apparently, the main pathogenetic mechanisms are associated with the polymetabolic disease itself – diabetes mellitus. Products of disturbed metabolic processes of proteins, glycoproteins, lipids enter hematogenously into the kidney and are deposited in its tissues.

The pathological anatomy of diabetic glomerulosclerosis is polymorphic. There are nodular, diffuse and exudative morphological forms. Some authors also distinguish a mixed form (A. M. Wierchert, 1972). The nodular form is described by Kimmelstil and Wilson and is considered specific for diabetes. It is characterized by the presence in the renal glomeruli of eosinophilic formations (nodules) of a round or oval shape, occupying part or all of the glomerulus. Nodules are clusters in the mesangium of various sized clumps and trabeculae, similar to the glomerular basement membrane substance and therefore called membrane-like. At the same time, there are expansion and aneurysm of the glomerular capillaries, thickening of their basement membranes. In the diffuse form of diabetic glomerulosclerosis, the morphological changes in the glomerulus are expressed in diffuse homogeneous expansion and compaction of the mesangium without the formation of typical nodules, but with the involvement of capillary basement membranes in the pathological process, which sharply thicken. Exudative changes are characterized by the appearance on the periphery of the lobules of the glomerulus rounded formations in the form of caps on capillary loops. An immunohistochemical study in these formations indicates a large number of complement-binding immunoglobulins, which made it possible to consider them immune complexes. The presence of typical nodules in combination with diffuse compression of the mesangium and thickening of the basement membranes of the glomerular capillaries is characteristic of a mixed form.

Secondary changes in diabetic glomerulosclerosis include lesions of the renal tubules with degenerative changes in the epithelium, hyalinization of the basement membranes, and fatty dystrophy. Along with the defeat of the glomerular capillaries, constituting the essence of diabetic glomerulosclerosis, signs of arteriosclerosis and atherosclerosis of the renal vessels are found. The outcome of all forms of diabetic glomerulosclerosis is complete desolation (death) of the glomerulosis and the development of periglomerular fibrosis.

Symptoms of Diabetic Glomerulosclerosis

There is no generally accepted classification of diabetic angiopathy. They are mainly based on individual clinical manifestations of vascular lesions (diabetic retinopathy, nephropathy) or are based mainly on morphological changes in organs.

According to the classification of N. F. Skopichenko (1973), there is a distinction between the initial (low symptom), transient (clinically distinct) and final (nephrotic-azotemic) stages of diabetic glomerulosclerosis. By the nature of the flow – slowly and rapidly progressing forms (options). Subsequent items of this classification indicate the possibility of combining diabetic glomerulosclerosis with microangiopathies of various localizations and the layering of other kidney diseases (pyelonephritis, amyloidosis).

The main symptoms of the disease are proteinuria, retinopathy and hypertension. Proteinuria is initially small and inconstant (from traces to 0.033 g / l), then it becomes permanent, moderately or significantly expressed (from 1.0-2.0 to 30 g / l). The most pronounced proteinuria is observed with a nodular type of lesion of the glomerular capillaries. However, in some patients with perennial diabetes, proteinuria may be absent (N. F. Skopichenko, 1972). One of the criteria for differential diagnosis of proteinuria of diabetic origin and proteinuria in pyelonephritis, congestive kidney and hypertension can be its degree (in diabetic glomerulosclerosis it is much greater than in pyelonephritis and hypertension) and, most importantly, the combination of hypertension with retinopathy.

Changes in urinary sediment (hematuria, cylindruria), especially with a disease duration of less than 10 years, are not significant. Only in the severe stage of the disease, especially with the nephrotic syndrome, is the corresponding cylindruria observed, while hematuria is insignificant. Waxy cylinders are observed only in the stage of renal failure.

Diabetic retinopathy occurs in 80% of cases and is characterized by pathological changes in the retina: microaneurysms, hemorrhages, exudates appear. Eye microaneurysms are so specific that even with their accidental detection it is necessary to exclude the presence of latent diabetes. Subsequent cicatricial retinal retardation may result in its detachment. All this leads to a significant weakening and loss of vision. It is believed that changes in the retinal vessels have a common genesis with a lesion of the glomerular capillaries, i.e. due to a lesion of the basement membranes. Sometimes retinopathy is ahead of nephropathy.

With the development of diabetic glomerulosclerosis, arterial hypertension becomes the main clinical sign. Unlike hypertension caused by hypertension and atherosclerosis, it is characterized by combination with progressive proteinuria and diabetic retinopathy. If the increase in blood pressure precedes diabetes or occurs simultaneously with it, then this indicates hypertension.

The pathogenesis of arterial hypertension in diabetic glomerulosclerosis is complex and is associated, in particular, with an increase in the activity of the renin-angiotensin-aldosterone system, which in turn is caused by damage to the small vessels of the kidneys – hyalinosis of the arterioles, the descent of most glomeruli and a decrease in renal blood flow (V. V. S , A. Ts. Anasashvili, 1983).

In the late stage, nephrotic syndrome is often associated with diabetic glomerulosclerosis, the clinic of which almost does not differ from that with kidney damage of a different etiology.

Uraemic syndrome in diabetic glomerulosclerosis occurs as a result of total failure of renal function and is clinically manifested by all the symptoms characteristic of the terminal stage of chronic renal failure. Uremia is considered the main cause of death for patients with diabetic glomerulosclerosis, mainly in young and middle age. Older patients die from various complications of atherosclerosis, before they reach the end stage of renal failure.

Diabetic glomerulosclerosis is accompanied by severe damage to the vessels of the heart, brain, lower extremities, up to the development of myocardial infarction, strokes and thrombosis, diabetic gangrene of the extremities. Polyneuritis is often observed. In the later stages of the disease, acute or chronic pyelonephritis can join it.

One of the features of diabetic glomerulosclerosis is the tendency, as the disease progresses, to a decrease in the glucose content in the blood and a decrease, up to a complete cessation, of glucosuria. This “remission” of diabetes is observed only in some patients and is not considered a mandatory symptom of the disease. The reasons for the disappearance of hyperglycemia are not entirely clear. It is believed that the decrease in glycemia can be explained by a decrease in the activity of renal insulinase, a decrease in the metabolic activity of protein-bound insulin and the formation of anti-insulin antibodies, hypoglycemic effect of the products of nitrogen metabolism, glucocorticoid insufficiency due to atrophy of the adrenal cortex bundle (EM Tareev, 1972; V. R. Klyachko, 1974).

In diabetic glomerulosclerosis, there is also a metabolic disorder of proteins, lipids, and protein-polysaccharide complexes. As the disease progresses, hypoalbuminemia and hypergammaglobulinemia increase, the total protein content in the blood decreases, mainly during the development of renal failure. The pathogenesis of dysproteinemia in diabetic glomerulosclerosis is not sufficiently clear, but is probably associated with insulin deficiency, which is necessary to maintain normal protein synthesis, loss of protein in the urine and impaired synthesis due to frequent liver damage in diabetes (P. Bodnar, 1974; B. C Yonushas, ​​N.A. Mkrtumova, 1976). There is also an increase in the concentration of potassium in the blood, an increase in the level of cholesterol, and an electrolyte imbalance with the possibility of developing hyperkalemia.

The features of the course of diabetic glomerulosclerosis include such symptoms as the gradual development of the disease, so its onset often goes unnoticed; scarcity of urinary sediment; reducing the severity of diabetes in some patients, as well as the combination of diabetes with other microangiopathies (especially with retinopathy and limb microangiopathies).

In diabetic glomerulosclerosis, the prognosis, despite active therapy, remains generally unfavorable.