Infective endocarditis and kidney damage: causes and pathogenesis

Infective endocarditis can cause various microorganisms, including fungi, rickettsia and chlamydia. However, bacteria are the causative agent first. The most frequent pathogens of infectious endocarditis are streptococci (50%) and staphylococci (35%). Other pathogens may be the bacteria of the group NASEC (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella ), enterococci, pseudomonas, gram-negative bacteria of the intestinal group, etc. In a small part of the patients (5-15%), it is not possible to isolate the pathogen in repeated bacteriological studies of the blood. The reason for this in most cases is the previous antibiotic therapy. Features of the pathogen can affect the nature of the flow and the clinical features of infective endocarditis. Subacute infective endocarditis of damaged valves is most often caused by bacteria with low virulence (green streptococcus). In acute infective endocarditis of intact valves, the main causative agent is Staphylococcus aureus, which is distinguished by high virulence. In recent years, there has been an increase in the incidence of infective endocarditis caused by Staphylococcus aureus, especially among intravenous drug users. This microorganism causes severe inflammation of the valves with their rapid destruction and the emergence of metastatic foci of infection in other organs. Fungal endocarditis develops in weakened patients who receive antibacterial and cytostatic therapy for a long time, as well as for drug addicts.

In the pathogenesis of infective endocarditis, an important role is played by 3 factors: the state of the organism, the circumstances leading to transient bacteremia, and the features of the pathogen (tropism and virulence).

• At the heart of the development of infective endocarditis is damage to the endothelium of the endocardium due to the impact of a turbulent blood stream moving at high speed and under high pressure. Changes in intracardiac hemodynamics in the presence of valvular lesions create additional prerequisites for the development of endothelial damage. As a result, platelets are activated in the damaged areas of the endocardium, accompanied by the deposition of fibrin and leading to the formation of thrombi, - non-tuberculous endocarditis occurs. Fixation on the damaged endocardium of microorganisms circulating in the bloodstream, followed by their multiplication in combination with continuing thrombosis leads to the formation of vegetation. Factors predisposing to infection of the endocardium are the existing pathology of the heart and the altered reactivity of the organism (due to intercurrent diseases, stress, hypothermia, etc.).
• Transient bacteremia can lead to the entry of microorganisms into areas of endocardial damage. Its causes are numerous: dental interventions (tooth extraction, tartar removal), surgeries on ENT organs (tonsillectomy, adenotomy), diagnostic procedures and surgical interventions on the urinary tract and gastrointestinal organs (cystoscopy, esophagogastroduodenoscopy, sigmoidoscopy), long-term use of venous catheters, the formation of vascular access for hemodialysis, intravenous infusions in non-sterile conditions, burns, pustular skin lesions, as well as a variety of intracardiac factors (cla panic heart defects, valve prostheses, pacemaker, etc.).
• Reproduction of bacteria in the formed vegetations promotes the growth of the latter and intracardiac spread of the infection, leading to the destruction of the valves. On the other hand, the further growth of microorganisms induces new episodes of bacteremia, the release of the antigen of the pathogen, the production of antibodies to it and the formation of immune complexes, the action of which is associated with the development of systemic manifestations of the disease (glomerulonephritis, myocarditis, vasculitis).

[1], [2], [3], [4], [5]

Features of glomerulonephritis in infectious endocarditis

Glomerulonephritis in infectious endocarditis is a classic immunocomplex glomerulonephritis. The triggering mechanism in its development is the entry of bacterial antigens into the bloodstream and the production of antibodies to them. In the future, either the formation of circulating immune complexes with subsequent deposition in the glomeruli of the kidneys, or fixation of antigens in glomeruli and the formation of immune complexes in situ are possible. Fixation of immune complexes in the glomeruli of the kidney causes complement activation and the production of a large number of cytokines as resident glomerular cells, as well as monocytes, macrophages, platelets (interleukin-1 and -2, PDGF, TGF-b), leading to glomerular damage and development of glomerulonephritis.

[6], [7], [8], [9], [10], [11]

Pathomorphology of kidney damage in infectious endocarditis

Depending on the nature of the course of infective endocarditis, focal (focal) or diffuse proliferative glomerulonephritis may develop.

• In patients with acute fulminant course of infective endocarditis, morphological changes are similar to those in acute postinfection glomerulonephritis and are manifested by diffuse endocapillary proliferation. Light-optical microscopy reveals a pronounced hypercellularity of all glomeruli, which is the result of the proliferation of resident cells, mainly mesangiocytes, and infiltration by neutrophils, monocytes / macrophages and plasma cells. In immunohistochemical studies, deposits of IgG and C3 components of complement, less often IgM on the basal membrane of the glomeruli, and in electron microscopy - subendothelial and subepithelial deposits.
• In subacute infective endocarditis, focal segmental proliferative glomerulonephritis with moderately expressed infiltrative changes in glomeruli is more often detected. Despite the focal nature of lesions in light-optical microscopy, immunofluorescence microscopy often reveals widespread and predominantly mesangial deposits of immunoglobulins.

The most characteristic morphological manifestation of glomerulonephritis in infectious endocarditis (as with other forms of septicemia, as well as visceral abscesses with a negative result of bacteriological blood examination) is the combination of endocapillary and extracapillary proliferation with the formation of semilunium. In the latter case, in immunofluorescence microscopy, in addition to deposits of the IgG and C3 complement components, deposits of fibrin in the composition of the semilunium are also revealed, indicating a necrotic nature of the process.

In addition to focal and diffuse proliferative glomerulonephritis with or without semimony, mesangiocapillary glomerulonephritis can develop in patients with infective endocarditis (especially with staphylococcal etiology of the disease). This morphological variant of glomerulonephritis is also characteristic of "shunt jade". A distinctive feature of postinfection mesangiocapillary glomerulonephritis is the presence of numerous deposits of the complement C3-component in the glomeruli. In all morphological variants of glomerulonephritis, tubulointerstitial changes are revealed: lymphoid infiltration and fibrosis of interstitium, atrophy of tubules. Massive antibiotic therapy exacerbates the severity of interstitial damage.

Classification of infective endocarditis

Depending on the duration of the flow, acute (up to 2 months) and subacute (more than 2 months) infectious endocarditis are distinguished.

• Acute infective endocarditis is a disease caused by highly virulent microorganisms, which occurs mainly with septic manifestations, frequent occurrence of purulent metastatic foci in different organs and without treatment leads to death within a few weeks.
• Subacute infectious endocarditis is a special form of sepsis, accompanied, in addition to septicemia, by embolisms and immune disorders, leading to the development of glomerulonephritis, vasculitis, synovitis, and polyserositis.

An extremely rare variant of the course of infective endocarditis is currently chronic, vschechlyaemoe with the duration of the disease for more than 1.5 years.

Depending on the previous state of the valvular heart apparatus, two large groups of infective endocarditis vscheljayut, having features of the course and treatment.

• Primary infective endocarditis arising on unchanged valves (20-40% of patients).
• Secondary infective endocarditis, developing on the affected heart valves (including rheumatic, congenital, atherosclerotic heart defects, mitral valve prolapse, after heart surgery) (60-80% of patients).

The current course of infective endocarditis is characterized by an increase in the frequency of its primary forms. Recently, the following 4 forms of the disease also vschelyayut:

• infectious endocarditis of natural valves;
• infectious endocarditis of prosthetic valves;
• infectious endocarditis in drug addicts;
• nosocomial infectious endocarditis.

[12], [13], [14], [15], [16]