Infective endocarditis and renal damage - Causes and pathogenesis

Infective endocarditis can be caused by various microorganisms, including fungi, rickettsia and chlamydia. However, bacteria are the primary causative agent. The most common causative agents of infective endocarditis are streptococci (50%) and staphylococci (35%). Other causative agents may be bacteria of the HASEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella ), enterococci, pseudomonads, gram-negative bacteria of the intestinal group, etc. In a small proportion of patients (5-15%), it is not possible to isolate the causative agent during repeated bacteriological blood tests. In most cases, this is due to previous antibacterial therapy. The characteristics of the causative agent may affect the nature of the course and 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 pathogen is Staphylococcus aureus, which is highly virulent. In recent years, an increase in the incidence of infective endocarditis caused by Staphylococcus aureus has been noted, especially among intravenous drug addicts. 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 have received long-term antibacterial and cytostatic therapy, as well as in drug addicts.

In the pathogenesis of infective endocarditis, three factors play an important role: the state of the body, the circumstances leading to transient bacteremia, and the characteristics of the pathogen (tropism and virulence).

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

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Features of glomerulonephritis in infective endocarditis

Glomerulonephritis in infective endocarditis is a classic immune complex glomerulonephritis. The trigger for its development is the entry of bacterial antigens into the bloodstream and the production of antibodies to them. Subsequently, either the formation of circulating immune complexes with their subsequent deposition in the glomeruli of the kidneys, or the fixation of antigens in the glomeruli and the formation of immune complexes in situ are possible. Fixation of immune complexes in the glomeruli of the kidney causes activation of complement and the production of a large number of cytokines by both resident glomerular cells and monocytes, macrophages, platelets (interleukin-1 and -2, TNF-a, PDGF, TGF-b), leading to damage to the glomeruli and the development of glomerulonephritis.

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Pathomorphology of renal damage in infective endocarditis

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

• In patients with acute fulminant infective endocarditis, morphological changes are similar to those in acute postinfectious glomerulonephritis and are manifested by diffuse endocapillary proliferation. Light microscopy reveals marked hypercellularity of all glomeruli, which is the result of proliferation of resident cells, mainly mesangiocytes, and infiltration by neutrophils, monocytes/macrophages, and plasma cells. Immunohistochemical studies reveal deposits of IgG and C3 complement component, less often IgM on the glomerular basement membrane, and electron microscopy reveals subendothelial and subepithelial deposits.
• In subacute infective endocarditis, focal segmental proliferative glomerulonephritis with moderately expressed infiltrative changes in the glomeruli is most often detected. Despite the focal nature of the lesion in light microscopy, immunofluorescence microscopy often reveals widespread and predominantly mesangial deposits of immunoglobulins.

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

In addition to focal and diffuse proliferative glomerulonephritis with or without crescents, patients with infective endocarditis may develop mesangiocapillary glomerulonephritis (especially with staphylococcal etiology of the disease). This morphological variant of glomerulonephritis is also characteristic of "shunt nephritis". A distinctive feature of postinfectious mesangiocapillary glomerulonephritis is the presence of numerous deposits of the C3 component of complement in the glomeruli. In all morphological variants of glomerulonephritis, tubulointerstitial changes are detected: lymphoid infiltration and fibrosis of the interstitium, tubular atrophy. Massive antibacterial therapy aggravates the severity of interstitial damage.

Classification of infective endocarditis

Depending on the duration of the course, a distinction is made between acute (up to 2 months) and subacute (more than 2 months) infective endocarditis.

• Acute infective endocarditis is a disease caused by highly virulent microorganisms, which occurs predominantly with septic manifestations, frequent occurrence of purulent metastatic foci in various organs and, without treatment, leads to death within a few weeks.
• Subacute infective endocarditis is a special form of sepsis, accompanied, in addition to septicemia, by embolism 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, which occurs when the disease lasts more than 1.5 years.

Depending on the previous condition of the heart valve apparatus, two large groups of infective endocarditis are distinguished, each with its own characteristics of course and treatment.

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

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

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

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