development of antibodies against transplant kidney after infection

Conditions: Acute Infection; Kidney Failure

Summary: kidney transplantation is the best method of renal replacement in patients with irreversible renal failure. one of the biggest problems today is premature loss of function of the transplanted kidney. this occurs most often on the basis of chronic humoral rejection. this is the immune response to the kidney, in which the specific antibodies play a crucial role (both against the hla and the non-hla system). the aim of this study is to analyze one of the situations where the production of antibodies can begin to occur. this is a serious acute infection (bacterial, viral, or fungal), where it is necessary to significantly reduce doses of immunosuppressives. at the time of reduced immunosuppression, the immune system can recognize the transplanted kidney as foreign to the human body and begin to fight against it. in this study, the investigators will monitor antibodies against the transplanted kidney in patients with severe acute infection. a serious infection in this study is one that requires acute hospitalization and reduced doses of immunosuppressive drugs. the researchers will measure the antibodies in the blood upon admission and then in 5 weeks.

kidney transplantation significantly improves the prognosis and quality of life of patients with irreversible renal failure (end-stage kidney disease), requiring hemodialysis or peritoneal dialysis. the length of the function of the transplanted kidney depends on a number of factors. one of the most significant deterioration factors and subsequent graft function failure, in the long run, is the production of antibodies against hla as well as transplant antigens that lead to acute or chronic humoral rejection. chronic humoral rejection leading to transplant glomerulopathy is the most common cause of loss of function of the transplanted kidney. treatment interventions in this area are still ineffective. in spite of immunosuppressive therapy, some patients develop anti-transplant antibodies (both against hla and non-hla antibody molecules) even with stable graft function. however, these patients have an increased risk of losing their function due to chronic humoral rejection. the hla-dr and hla-dq molecules have the greatest immunogenicity. patients after kidney transplantation may have many complications. both surgical (vascular anastomoses stenoses, wound healing problems, graft vascular thromboses, lymphocele, urinary leakage) and non-surgical, some of which are immune-compromised (rejection) and others, result from the mechanism of action of immunosuppressive preparations (infections, cardiovascular effects). amongst potentially life-threatening conditions include acute infections. immunosuppressed infections have their own specifics. in addition to the increased risk of infections; also a different spectrum of possible originators is known. it is also possible to encounter opportunistic infections - pneumocystis, cytomegalovirus, polyomavirus infections. another specific feature is often a different course of infection - patients may not have significantly expressed clinical or laboratory findings and may progress rapidly. for these reasons, physicians are often forced to significantly reduce immunosuppression rates in patients with acute infection, despite the increased risk of developing rejection. this situation increases the risk of initiation by both cell-mediated rejection and antibody-mediated rejection. signs of rejection are very nonspecific and the only diagnostic method is graft biopsy. previous studies have shown that the production of antibodies to the transplanted kidney is preceded by clinical signs of deterioration in graft function over weeks to months. patients included in the study according to the criteria will be examined for the presence of hla antibodies and non-hla on admission (within 48 hours of admission) and 5 weeks after the first sample method luminex xmap.

Eligibility criteria:
inclusion criteria: * age 18 years and over. * a kidney transplant patient - from a living donor or from a cadaveric donor (donor after circulatory or brain death). the patient will be included after 1st transplant and possible retransplantation. * the patient is hospitalized or newly admitted to the fn ostrava internal clinic for acute infection + requires the reduction of immunosuppressive therapy (dose reduction or discontinuation of any of the maintenance immunosuppressive preparations - tacrolimus, cyclosporin a, sirolimus, everolimus, azathioprine, mycophenolate). * acute infection (to be admitted to an internal clinic - determine the time of admission or the time of the first symptom of infection in the already hospitalized) occurred at least more than 48 hours after transplantation (from reperfusion time) and a maximum of 10 years after transplantation. * the patient did not receive intravenous immunoglobulins within the last 24 hours prior to first sampling. * this is not a pregnant woman. exclusion criteria: * patient's death before the 2nd blood sampling. * the patient condition was conclusively determined as something other than acute infection (acute rejection episode, acute pancreatitis, malignant tumor, ...). unfamiliarity with localization of the infection or its origin, assuming an infectious etiology, is not an exclusion criterion. * the patient was graftectomized - removal of the transplanted kidney, between the 1st and 2nd antibody determination. * detection of pregnancy when the term of conception is calculated before the 2nd antibody count. * one or more transfusions of the erythrocytes or plasma between the 1st and 2nd measurements were administered to the patient.

Keywords: kidney transplant hla antibodies acute infection