Transplantation Immunology
The prognosis of kidney disease is primarily related to the development of a deficiency in the functional capacity of the kidneys. That is why special studies are conducted to study the risk factors for the progression of nephropathies and the formation of chronic renal failure. At present, it is clearly defined that the child's risk of developing chronic renal insufficiency is the presence of signs of structural renal dysembryogenesis( a violation of the development of renal tissue) in the child, which can depend on genetic and teratogenic influences. The risk groups of chronic renal failure in children include many congenital diseases of the kidneys.
One of the main methods of treatment of chronic renal failure in hereditary and congenital kidney diseases is renal transplantation. However, when deciding on the question of kidney transplantation, parents should be examined as possible donors, since they may have a genetic defect in a latent form.
Transplants can be divided into 4 groups:
1) autologous( taken from the same individual), which is not performed with renal transplantation;
2) syngeneic( taken from an immunogenetically identical individual, for example, from an identical twin);
3) allogeneic( from an individual of the same species immunologically distinct from the recipient);
4) xenogenic( from an individual of another biological species, immunologically distinct from the recipient).
When performing autotransplantation from a monozygotic twin, there is no immunologically conditioned rejection of the graft. For the difficulties arising during organ transplantation in conditions of allogenic and xenogenic transplantation, antigens of compatibility of tissues of various living organisms are responsible. The sum of all transplantation antigens controlled by a specific genetic locus represents a tissue compatibility system.
Genetically programmed antigens - HLA systems( histocompatibility genes, ie, tissue compatibility among themselves) represent the biggest obstacle to successful allogeneic kidney transplantation. The number of currently known( several dozen) different antigens makes it possible to realize a very large number of combinations.
Another set of systems( small tissue compatibility complex) is important for transplantation, they should be considered when selecting a donor and a recipient. This includes the blood groups ABO, Rh-factor and Lewis-factor, since they occur not only in red blood cells, but also in other cells. Antibodies, located inside cells, play a more subordinate role in transplantation.
Some immunological processes are very important for kidney transplantation. Immunological tolerance( tolerance), which is observed in the fetus or in a newborn child, can be achieved and with a special immunological effect on the body of an adult. One such method is ionizing irradiation of the whole body with subsequent replacement of the bone marrow.
Many mechanisms may be suitable for this purpose, for example preventing the release of foreign antigens to the recipient( i.e., the person to whom the donor organ transplant is transplanted) antigens from the graft, preventing an immune response to transplant antigens, or protecting the organ with specific antibodies. The successes achieved in improving measures aimed at preventing graft rejection are closer to practice than the hopes for achieving full immunotolerance( immunity tolerance of the recipient in the transplantation of donor organs and tissues).
Along with steroids( hormonal drugs) and cytostatics in renal transplantation, a great warning value for the prevention of rejection is cyclosporin A.
Treatment. Treatment of kidney diseases associated with genetic and teratogenic( pathogenic to the fetus during the prenatal period), is a very complex but not a hopeless task.
The number of diseases affecting the organs of the urinary system that can be diagnosed using antenatal( antenatal) diagnostic methods is small. However, in connection with the development of fetal surgery( fetal surgery) the possibility of identifying severe congenital malformations with ultrasound methods is becoming increasingly important. Among the various vices that can be diagnosed by echolocation of the fetus, undoubtedly, promising is the detection of malformations of the organs of the urinary system. With increasing frequency, the literature reports on the success of surgical intervention even in the presence of a child suffering from a hereditary disease in the womb. In addition to such a non-invasive method as ultrasound, amniotic and fetoscopy, contrast radiography, chorion cell biopsy and amniocentesis with subsequent cytogenetic, biochemical and immunological investigation of the amniotic fluid and cell culture are currently used for prenatal diagnosis. Timely determination of α-fetoprotein in amniotic fluid practically solved in Finland the problem of the Finnish variant of congenital nephrotic syndrome. The determination of α-fetoprotein for the diagnosis of such a severe syndrome with renal polycystosis, such as Meckel syndrome, is equally promising. In families of high-risk groups similar to this type of research is carried out in pregnant women, and if the protein is detected, the pregnancy is interrupted in due time. In those cases when the diagnosis of a monogeneously inherited disease in a child is confirmed, the decision to give birth to the child must be taken by the family, which causes many ethical problems. The latter is due in large part to the fact that the idea of the fatalities of urinary tract disease in the population is minimal, and the disease can manifest not only in childhood, but also in later age periods. As the development of medicine and clinical genetics in the future will be possible to affect the level of DNA cells.
Palliative effects are currently used. Diet therapy is widely used, which is called "environmental engineering".In particular, with oxalate nephropathy, the antioxaluric diet is widely used, which is recommended to be used by 3-4 non-long courses at an early age when signs of oxalate diathesis are found. This diet is recommended for the next of kin, since the origins of the disease are family.
Palliative methods of therapy are the use of drugs that stabilize the membranes of body cells, thus preventing the development of many pathological processes. These drugs include diphosphone, xidiphon, as well as complexes of B, A and E vitamins, which are also antioxidants. Improvement of kidney function is achieved using ATP, cocarboxylase, which is shown in some variants of renal dysembryogenesis( disorders of intrauterine development of the kidneys).With the development of nephropathy( renal pathology) due to impaired purine metabolism, allopurin is widely used, which blocks the formation of uric acid. This is clinically manifested after 24-48 hours by a decrease in urate levels in the blood and urine. However, one should remember about a possible complication - an increase in the level of xanthine in the blood, which is fraught with its complications.
Diagnosis of a hereditary or congenital pathology without stratification of kidney damage in cases of immune system disorders also involves limiting therapeutic activity, primarily in terms of the use of steroid drugs( hormones) and immunosuppressants( drugs that reduce the activity of the immunity system).Immunosuppressants and corticosteroids are contraindicated in hereditary nephritis, apparently because they can cause a disruption in the balance of those adaptation mechanisms that develop in cases of renal disease of genetic origin. The detection of signs of structural disorder in the kidney biopsy is a contraindication for the appointment of indomethacin, since in such children a decrease in renal functions is revealed. With the development of the terminal stage of chronic renal failure in children with hereditary and congenital nephropathies, kidney transplantation can be performed leading to a distinct improvement in the condition of patients, in part dependent on the fact that the transplanted organ compensates for the missing synthesis of proteins and enzymes that are absent or present in minimal amounts in hereditarykidney damage. However, there is now evidence of the possibility of developing rapidly progressive glomerulonephritis in individuals with Alport syndrome after renal transplantation, which is associated with the presence in the transplant of the antigen that was absent in patients before organ transplantation. Growth hormone is used to improve the development of children with a kidney transplant. Children who are on dialysis are treated with erythropoietin( a substance that stimulates the formation of bone marrow and a release into the bloodstream of mature red blood cells), the use of which also solves the problem of treating anemia.
In connection with the small possibilities of drug therapy of hereditary nephropathies, the problems of prevention of their development are put on the first place. At present, a range of diseases and conditions is defined in which it is necessary to conduct medical genetic counseling in terms of possible development of the pathology of the urinary system. The tasks of medical genetic counseling include both determining the role of heredity in the development of a detected nephropathy, and determining the prognosis of morbidity in offspring. All these issues are increasingly being studied in nephrology and should be the subject of close attention of a pediatrician, a nephrologist, an obstetrician-gynecologist and a urologist.