Post-transplant complications

Contraindications to transplantation

Absolute contraindications to transplantation are active infection, neoplasms (with the exception of hepatocellular carcinoma, limited to the liver) and pregnancy. Relative contraindications are age over 65 years, serious functional disorders and eating disorders (including severe obesity), HIV infection, multiple organ failure, metabolic disorders, high probability of non-transplantation. The decision on the possibility of transplantation for patients with relative contraindications differs in different medical centers; In HIV-infected patients who underwent transplantation, the use of immunosuppressants is safe and effective.

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Rejection after transplantation

Rejection of solid organs can be fulminant, accelerated, acute or chronic (late). These types of rejection to some extent overlap in time, but differ in the histological picture. The symptomatology of rejection varies depending on the organ.

Fulminant rejection begins within 48 hours after transplantation and is caused by pre-existing complement-binding antibodies to transplant antigens (pre-sensitization). Once pre-transplantation screening has been established, this rejection happens rarely (1%). Hyperostroic rejection is characterized by thrombosis of small vessels and a transplant infarction. No treatment has an effect, except for transplant removal.

Accelerated rejection begins 3-5 days after transplantation; its cause is the presence of pre-existing non-complement-binding antibodies to transplant antigens. Accelerated rejection is also a rare occurrence. Histopathologically it is characterized by cellular infiltrates with or without vascular changes. Treatment consists in the appointment of pulse therapy with high doses of glucocorticoids or, if there are vascular changes, antilymphocytic drugs. Used plasmapheresis, which helps to quickly remove circulating antibodies.

Acute rejection is the destruction of the transplant from the 6th day to the 3rd month after transplantation and is the result of a T-mediated delayed hypersensitivity reaction to the histocompatibility antigens of the allograft. This complication accounts for half of all cases of rejection that occur within 10 years. Acute rejection is characterized by mononuclear cell infiltration with varying severity of hemorrhage, edema and necrosis. Vascular integrity is usually maintained, despite the fact that the primary target is the endothelium of the vessels. Acute rejection often undergoes reverse development against a background of intensive immunosuppressive therapy (for example, pulse therapy with glucocorticoids and ALG). After suppression of the rejection reaction, the significantly damaged parts of the graft are replaced by the areas of fibrosis, the graft remnants are functioning normally, the doses of immunosuppressants can be reduced to low, the allograft can survive for a long time.

Chronic rejection is transplant dysfunction, often without fever, usually begins months or years after transplantation, but sometimes even for several weeks. The causes can be very diverse and include early antibodies-mediated rejection, ischemia around the transplant area, reperfusion injury, drug toxicity, infections, vascular disorders (hypertension, hyperlipidemia). Chronic rejection constitutes the second half of all cases of rejection. Proliferating neointima, consisting of smooth muscle cells and extracellular matrix (transplantation atherosclerosis), gradually eventually clogs the lumen of the vessel, which leads to fragmentary ischemia and fibrosis of the graft. Chronic rejection progresses gradually, despite immunosuppressive therapy; no treatment with proven effectiveness does not exist.

Infections

Immunosuppressants, secondary immunodeficiency conditions that accompany organ damage, and surgical intervention make patients more prone to infections. More rarely, the source of infection is the transplanted organs (eg, cytomegalovirus).

Common signs are fever, often without signs of localization of the process. Fever may be a symptom of acute rejection, but is usually accompanied by signs of graft dysfunction. If these signs are absent, then the approach is the same as with other fevers of unknown origin; The time of onset of symptoms and objective signs after transplantation will help in differential diagnosis.

In the first month after transplantation, the cause of most infections is hospital flora and fungi, which infected other surgical patients (for example, Pseudomonas sp, causing pneumonia, gram-positive flora, causing infection of wounds). The greatest concern from the point of view of early infection is caused by those microorganisms that can infect the transplant or its vascular system at the site of the suture, which leads to the development of a mycotic aneurysm or seam divergence.

Opportunistic infections occur 1-6 months after transplantation (see the reference for treatment). Infections can be bacterial (eg, listeriosis, nocardiosis), viral infections (due to infection with cytomegalovirus, Epstein-Barr virus, varicella zoster virus, hepatitis B and C viruses), fungal (aspergillosis, cryptococcosis, Pneumocystis jiroveci infection ) or parasitic (strongyloidiasis, toxoplasmosis , trypanosomiasis, leishmaniasis).

The risk of infection after 6 months is reduced to the general population level in about 80% of patients. About 10% of patients have complications of early infections, such as viral infection of the transplant, metastatic infections (cytomegalovirus retinitis, colitis) or virus-induced tumors (hepatitis and hepatocellular carcinoma, human papillomavirus, basal cell carcinoma). The remaining patients develop chronic rejection, which requires high doses of immunosuppressants (from 5 to 10%), and the risk of developing opportunistic infections is constantly high.

After transplantation, most patients receive antibiotics to reduce the risk of infection. The choice of the drug depends on the individual risk and type of transplantation; the treatment regimen includes trimethoprim-sulfamethoxazole 80/400 mg orally once a day for 4-12 months to prevent infection of Pneumocystis jiroveci or urinary tract infections in patients with kidney transplantation. Patients with neutropenia are prescribed quinolone antibiotics (levofloxacin 500 mg orally or intravenously once a day) to prevent infection with Gram-negative flora. The appointment of inactivated vaccines in the posttransplant period is safe; the risk of prescribing live attenuated vaccines should be compared with the potential benefit of their use, especially in patients receiving low doses of immunosuppres- sants.

Renal impairment

The glomerular filtration rate is reduced from 30 to 50% during the first 6 months after organ transplantation in 15-20% of patients. Usually they also develop hypertension. These disorders are most typical for recipients of intestinal grafts (21%) and are least characteristic for heart and lung transplantation (7%). The nephrotoxic and diabetic effects of calcineurin inhibitors, as well as stroke of the kidney around the graft site, pre-transplantation kidney failure or hepatitis C, the use of nephrotoxic drugs, make an undeniable contribution. After initial reduction, the glomerular filtration rate usually stabilizes or decreases more slowly; However, the risk of death is increased fourfold, if there is no subsequent kidney transplantation. Renal failure after transplantation can be prevented by early cancellation of calcineurin inhibitors, but a safe minimum dose is unknown.

Oncological diseases

Long-term immunosuppressive therapy increases the frequency of virus-induced tumors, especially squamous (squamous) and basal cell carcinoma, lymphoproliferative disease (mainly B-cell non-Hodgkin's lymphoma), anogenital (including cervical) cancer, Kaposi's sarcoma. Treatment is the same as in patients who have not undergone transplantation; for tumors of a low degree of malignancy, a decrease or suspension of immunosuppressive therapy is usually not required, but in aggressive tumors or lymphomas it is recommended to do so. Currently, the possibility of transfusion of partially HLA-related cytotoxic T-lymphocytes as a possible treatment for some forms of lymphoproliferative disease is being investigated. Such patients are recommended bone marrow biopsy.

Other complications of transplantation

Immunosuppressants (especially glucocorticoids and calcineurin inhibitors) increase bone resorption and increase the risk of osteoporosis in patients who have a similar risk before transplantation (for example, due to reduced physical activity, consumption of tobacco and alcohol, or pre-existing renal impairment). Although their purpose is not routine, a certain role in the prevention of these complications can play vitamin D, bisphosphonates and other antiresorptive drugs.

The problem in children is disruption of growth, mainly as a consequence of prolonged glucocorticoid therapy. This complication can be controlled by a gradual reduction in the dose of glucocorticoids to a minimum level that does not allow rejection of the transplant.

Systemic atherosclerosis can be a consequence of hyperlipidemia due to the use of inhibitors of calcineurin and glucocorticoids; it usually manifests itself more than 15 years after kidney transplantation.

Graft-versus-host disease (GVHD-graft vs host disease) occurs when the activity of donor T-lymphocytes is directed against the recipient's own antigens. BTPX primarily affects the hematopoietic stem cells of the recipient, but can also affect the liver and transplant of the recipient's small intestine