Staged desensitizing therapy for complex preoperative preparation of candidates for organ (liver/kidney) transplantation with high immunological risk

Relevance

For patients with end-stage kidney and liver disease, kidney/liver transplantation is the gold standard of care, not only saving a life but also significantly improving quality of life. Patients with end-stage kidney/liver disease with a history of repeated pregnancies, blood transfusions, and organ/tissue transplants belong to a cohort of patients at high immunological risk. Highly sensitized transplant candidates face limited access to donor organs due to their high immunological risk. Sensitization is one of the main obstacles to the successful outcome of transplantation, often leading to antibody-mediated rejection. Many recipient sensitization cases are associated with an increase in the duration of waiting for a donor organ, which leads to exclusion from the waiting list due to the death of patients.

Nowadays desensitizing protocols are used in the world, including plasmapheresis sessions, administration of monoclonal antibodies, and intravenous immunoglobulin. However, in our republic, desensitizing protocols in organ transplantation are not used and have not been introduced into national protocols for organ transplantation. It was a prerequisite for the project for the scientifically based implementation of desensitizing protocols in our country.

Purpose of the project

To evaluate the effectiveness of desensitizing protocols in the complex preparation of candidates for transplantation, which will lead to an increase in the pool of donors for highly sensitized recipients.

Project objectives

• To estimate the proportion of highly sensitized organ transplant candidates among the total number of patients.
• To define criteria for including patients in the high immunological risk group.
• To develop an algorithm for examining a recipient/donor in a group with a high immunological risk.
• To determine indications for desensitization
• To develop approaches to overcome the immunological barrier of recipients. To develop desensitizing protocols for patients at high immunological risk.
• To evaluate the effectiveness of desensitizing protocols in liver/kidney transplantation in highly sensitized patients.
• To estimate the incidence of hyperacute and acute rejection within two weeks after organ transplantation.

Expected results

1. Reducing the immunological risk in patients on the waiting list and candidates for transplantation with an intravital and posthumous donor.
2. Reducing the risk of hyperacute and acute rejection in renal/liver transplant recipients
3. Improvement of graft and recipient survival rates after liver/kidney transplantation
4. Publication of 3 articles in an international journal (impact factor 0.5-5.0; target journals Transplant International (impact factor-3.177, cite score percentile - 70) Transplantation Proceedings (impact factor-0.784. Cite score percentile-40%; Transplantation Reviews (impact factor-3.262. cite score percentile 81%)
5. Publication of the article in editions recommended by CQAES MES RK (target journals – Clinical Medicine of Kazakhstan, Astana Medicine Journal)
6. Based on the principles of evidence-based medicine as a result of the proposed project, the development, and implementation of a protocol for desensitization of kidney/liver recipients into the national protocols for kidney/liver transplantation
7. Development and publication of a methodological manual on desensitization of candidates for organ transplantation with high immunological risk
8. Conducting training seminars among transplant doctors on the effectiveness of the use of desensitizing protocols for a group of patients with high immunological risk.

Investigators

Abdrakhmanova Saniya, ORCID: 0000-0003-0782-1795 URL:  https://orcid.org/0000-0003-0782-1795

Asykbayev Mels Nurseitovich, ORCID: 0000-0003-2386-0997  URL: https://orcid.org/0000-0003-2386-0997

Abdugafarov Saitkarim Abdugapirovich, ORCID: 0000-0002-8393-9966 URL: https://orcid.org/0000-0002-8393-9966

Spatayev Zhanat Seitbatallovich, ORCID: 0000-0003-1659-431X URL: https://orcid.org/0000-0003-1659-431X

Zheksembayev Asan Aitmukashevich

Saparbay Jamilya Zhumabekovna, ORCID: 0000-0002-8478-5452 URL: https://orcid.org/0000-0002-8478-5452

Akhmetova Dana Meiram-Batyrovna

Zhakhina Gulnur Talgatovna, ORCID: 0000-0002-1001-1374 URL: https://orcid.org/0000-0002-1001-1374

Zhangaziyeva Kuralai, ORCID: 0000-0002-2005-006X URL: https://orcid.org/0000-0002-2005-006X

Turganbekova Aida, ORCID: 0000-0002-1514-5910 URL: https://orcid.org/0000-0002-1514-5910

Tuyakova Nurlygul, ORCID: 0000-0002-8987-0429 URL: https://orcid.org/0000-0002-8987-0429

Parkhomenko Elena Alexandrovna

Adilbayeva Aigerim Shahapovna

Zhanzakova Zhuldyz Zhetpisbayevna

Achieved results

For the period from March 2021 to November 2021, 19 patients with an established diagnosis of Chronic Kidney Disease (stages 4-5) were included in the study.

Of the 19 patients who were included in the study, at the stage of questioning and medical examination, one was excluded due to contraindications. When determining the compatibility of patients (cross-match) for desensitization by a blood test, 5 showed incompatibility with a potential donor, but after repeated cross-match with the DTT reagent, their results came out negative. The abovementioned patients underwent organ transplantation, they did not undergo the stages of desensitizing therapy. These patients were discharged without acute and hyperacute rejection, in satisfactory condition.

As a result, 13 patients were included in the desensitizing therapy, of which men (5) and women (8) accounted for 38.5% and 61.5%, respectively. The average age of the patients who were included in the study was 44.8 years, ranging from 25 to 58 years.

Although patients do not show a significant difference in the level of leukocyte antibodies after 1 stage of desensitizing therapy and one session of plasmapheresis, there is a significant decrease after repeated sessions of plasmapheresis.

List of scientific products for 2021:

1. «Malignant neoplasm of renal allograft». Saparbay J. Report. VIII Congress of Oncologists and Radiologists, October 14-16, 2021, Turkestan, Kazakhstan.
2. «Kidney transplantation: 10-year experience of LLP National Cancer Research Center». Asykbayev M. Report. VII Congress of Surgeons of Kazakhstan with International Participation «Surgery: yesterday, today, tomorrow». September 30 – October 1, 2021. Almaty.
3. «Renal transplant carcinomas», Saparbay J. Report. VII Congress of Surgeons of Kazakhstan with International Participation «Surgery: yesterday, today, tomorrow». September 30 – October 1, 2021. Almaty.
4. «Results of AB0 incompatible liver transplantation». Spatayev Zh. Report. VII Congress of Surgeons of Kazakhstan with International Participation «Surgery: yesterday, today, tomorrow». September 30 – October 1, 2021. Almaty.
5. «The role of leukocyte antibodies in organ transplantation», poster presentation (Zhanzakova Zh., Abdrakhmanova S., Turganbekova A.). Sent to the V National Congress "The Globality of Nephrology: Priority Directions and Strategic Approaches", which will be held on November 19-20, 2021. G. Nur-Sultan, Kazakhstan.
6. Saparbay J., Assykbayev M., Abdugafarov S., Zhakhina G., Spatayev Zh., Zhexembayev A., Zhanzakova Zh., Turganbekova A., Abdrakhmanova S., Kulkayeva G. (2021). Desensitization in kidney transplantation: review. Journal of Clinical Medicine of Kazakhstan.

День семьи был учрежден в Казахстане в 2013 году и с того момента отмечается каждое второе воскресенье сентября. В 2021 году эта дата приходится на 12 сентября.

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Employees of the LLP "National Research Oncology Center" participate in the development of clinical protocols. 6 clinical protocols were prioritized in the Republican state enterprise on the right of economic management "National Scientific Center for Health Development named after Salidat Kairbekova". (Order of MH RK № 404 from 09.07.2021

Clinical protocol for diagnosis and treatment of esophageal diverticulum in adults

Peripheral T-cell lymphomas

Hodgkin lymphoma

Conducting telemedicine consultations in our center has been practice since the introduction of this technology in the health care system of Kazakhstan. Obtaining high-quality qualified medical care using remote information technologies is especially relevant and indispensable for cancer patients from remote regions and those who have difficulties with movement. Reducing the distance and time allows you to quickly consider complex clinical cases, and in oncology, simple diagnoses, as a rule, do not exist.

At present, taking into account the imposed restrictive measures related to the epidemiological situation in the country and in the world, the demand for telemedicine has only increased.

In order to receive a consultation through telemedicine, you need to take the following steps:

1. Contact your attending physician at the primary health care organization where the patient is assigned or at the territorial cancer center. The attending physician will prepare an extract, attach the results of clinical and instrumental examinations and send them to our Center, the telemedicine coordinator.
2. The coordinator will study the submitted documents and send them to specialized specialists to resolve the issue of conducting a telemedicine consultation, after which he will contact the medical organization or directly with the attending physician who referred the patient and inform about the date and time of the remote consultation. If additional examinations are necessary, the patient will also be informed by the referring medical organization or the attending physician.
3. On the appointed day and time, the patient must arrive at the medical organization that organizes this telemedicine session.

Telemedicine consultations are provided free of charge. It should be noted that the patient must necessarily be attached to the PMSM organization, since it is not possible to independently receive a remote consultation without the accompaniment of the attending physician.

During the consultation itself, specialized specialists or a multidisciplinary group (depending on the complexity of the diagnosis) will decide the question of further treatment tactics and, if necessary, hospitalization in the NNOC hospital.

Early diagnosis of stomach cancer

Periodic examination of the stomach is recommended to detect latent and early forms of gastric cancer.

Risk factors for stomach cancer:

• Helicobacter pylori infection;
• hereditary predisposition;
• polyps of the stomach;
• peptic ulcer, chronic gastritis, dysplasia of the gastric mucosa;
• duodenogastric reflux;
• bad habits: smoking and alcohol abuse;
• hypo- and hyper-vitaminosis;
• poor nutrition;
• eating disorder;
• other diseases of the gastrointestinal tract.

If there is at least one risk factor, the recommendation for examination is more urgent. However, this does not mean an obligatory negative outlook for the development of a tumor disease.

Diagnosis of precancerous and neoplastic conditions of the stomach includes:

• examination by a therapist, gastroenterologist, oncologist;
• endoscopic diagnostics (gastroscopy, gastroduodenoscopy, fibrogastroduodenoscopy, VEGDS);
• X-ray of the stomach;
• ultrasound of the abdominal segment. If an additional examination is necessary, the NSC has all the clarifying diagnostic high-tech methods.

Modern medicine has sufficient capabilities for the treatment of malignant stomach pathologies.

Anxiety symptoms for which it is advisable to think about the need for examination:

• fatigue, weakness;
• nausea and belching;
• decreased appetite;
• feeling of discomfort in the abdomen.

At the National Scientific Oncological Center, it is possible to examine the gastrointestinal tract as part of the Check-up "Gastroenterological" package.

Screening for prostate cancer

Doctors at the National Research Oncology Center strongly recommend to get screened for prostate cancer on time, regardless of symptoms.

The following guidelines for screening for prostate cancer apply to most men.

Risk factors for prostate cancer:

• • Age: this is the most important risk factor. More than 90% of cases occur in men aged 45 and over.
• • Family history: the risk is higher if your close relatives (especially first-line relatives - father, brother, son) have or have had prostate cancer, also if they were diagnosed with this disease at a younger age. Men in this category must be examined without fail at the age of 40 and older.
• • Hereditary cancer syndromes: Certain genetic mutations increase the risk of prostate cancer in men. These include Lynch syndrome and mutations in the BRCA1 and BRCA 2 genes.
• • Race: African Americans are almost twice as likely to have prostate cancer as whites. Less common in Asians.
• • A diet high in fat, especially animal fat, can increase the risk.
• • Nationality: Prostate cancer is more common in North America and Northwest Europe than in other parts of the world.
• • Inflammation of the prostate (prostatitis) and sexually transmitted diseases (STDs).

Initial examinations for men, which are recommended to undergo from 45 years of age at least once a year on a regular basis:

• • Blood test for prostate-specific antigen (PSA);
• • Examination by a urologist (digital rectal examination);
• • TRUS (transrectal ultrasound) of the prostate gland.

Examinations for high-risk men:

! If at least one of the above factors is relevant to you, it does not mean that you will definitely get cancer. However, you may need to start the test at an earlier age or get it done more often, as men at higher risk are more likely to develop prostate cancer.

Basic (mandatory) diagnostic examinations:

• •General blood analysis;
• •General urine analysis;
• • Biochemical blood test (protein, urea, creatinine, glucose);
• • Determination of total PSA (prostate - specific antigen) - Total, free and serum index by immunochemiluminescence;
• • X-ray examination of the lungs;
• • ultrasound of the pelvic organs with the determination of residual urine;
• • TRUS-guided prostate biopsy with morphological verification of the diagnosis.

If necessary, the doctor can send for additional examinations.

!!! Often, patients expect symptoms, but they do not occur with prostate cancer. Symptoms such as frequent urination and blood in the urine do not always indicate oncopathology, they also occur with prostate adenoma and chronic prostatitis. Prostate cancer is detected only on the basis of laboratory diagnostic tests.

Based on the NROC, you can get a complete examination as part of the Check-up package "Men's health".

At the NROC, you can undergo high-quality diagnostics, get a "second opinion" about the type of tumor cells in the diagnosis, and, if necessary, immediately begin and receive qualified treatment.

KIDNEY CANCER

Kidney cancer is a malignant tumor of the kidney, which is most often carcinoma and develops either from the epithelium of the proximal tubules and collecting tubules, or from the epithelium of the calyceal system.

In Kazakhstan, about 1200 cases of malignant neoplasms are detected for the first time in their lives every year. In the structure of incidence, kidney cancer ranks 8th. Every year 250 thousand people fall ill in the world and about 100 thousand people die from renal cell cancer.

Causes of the disease and risk factors:

• • Age. It is most often diagnosed in people aged 50-70 years - Hippel-Lindau syndrome. Inherited gene mutations can increase the likelihood of developing kidney cancer.
• • Gender. Men are twice as likely to develop kidney cancer as women.
• • Exposure to chemicals. Certain chemicals - asbestos, cadmium, organic solvents - can significantly increase the risk of developing.
• • Prolonged dialysis. In patients on long-term dialysis, cysts may appear in the kidneys, which can contribute to the development of cancer of this organ.
• • Smoking. The risk of getting kidney cancer in smokers is 2 times higher than in non-smokers.
• • Overweight. Eating high-calorie foods that promote obesity increases your risk of getting sick.

The presence of risk factors does not mean that a kidney tumor will necessarily appear, but may increase your chance of developing kidney cancer.

Kidney cancer symptoms:

In the early stages, symptoms may not appear. It should be noted the symptoms of kidney cancer, which may indirectly indicate a possible disease:

• • hematuria (blood in the urine);
• • the presence of swelling in the lumbar region, which can be detected by palpation;
• • deterioration in general condition, weakness, lethargy, loss of appetite;
• • increased body temperature;
• • swelling of the legs;
• • anemia;
• • an unreasonable increase in blood pressure;
• • painful sensations in the kidney area.

In several tens of percent of cases, kidney cancer does not show symptoms in any way and is detected quite by accident - during a preventive examination or performing an ultrasound examination of the abdominal cavity organs (ultrasound) for some other disease. Only an experienced specialist can detect the disease at an early stage or confirm its absence.

Diagnostics:

When making a diagnosis of kidney cancer, the following research methods are used:

• • ultrasound examination, helps to distinguish a tumor from another formation;
• • X-ray diagnostics: radiography (including renal angiography, urography, etc.);
• • CT scan;
• • laboratory tests of blood and urine.

In difficult cases, when other studies are not informative, the latest PET-CT examination method is used for diagnosis.

It should be noted that tumor biopsy is contraindicated as it can provoke the spread of the disease.

Doctor's recommendations for the prevention of kidney cancer:

The main prevention of the disease is to quit bad habits such as smoking, alcohol abuse. Also, if possible, it is necessary to avoid contact with chemicals (asbestos, cadmium, etc.). Adhere to the basic rules of a healthy diet, an active lifestyle,

If you have any symptoms or want to get tested, you can call our Call Center 8 (7172) 702-911. Here, you can get qualified advice from both oncologists and transplantologists and a full range of diagnostic services and determination of treatment tactics.

Tests for liver cancer

Hepatocellular carcinoma (HCC) is a primary malignant tumor from hepatocytes. HCC is the most common malignant tumor of the liver and makes a significant contribution to mortality from cancer in the world (fifth place).

Liver cancer screening is currently only recommended for high-risk adults. This is because they are more likely to get sick.

Having an increased risk does not mean that you will definitely get liver cancer. But you may need to start regular screenings to help detect cancer at the earliest possible stage in the event of illness. With early detection, the chances of a successful cure of the disease are high.

Along with regular examinations, watch for changes in the body. So it is worth being alert if you notice yellowness or weight loss and immediately inform your doctor about it.

Risk factors:

• Chronic infection of hepatitis B and C;
• Primary biliary cirrhosis (PBC);
• Hereditary metabolic disorders, including:
• Hemochromatosis
• Alpha-1 antitrypsin deficiency
• Glycogen storage disease
• Cutaneous porphyria late
• Tyrosinemia
• Autoimmune hepatitis;
• Non-alcoholic fatty liver disease (NAFLD).

If any of these factors are relevant to you, it is imperative that you see your doctor, who will send you for certain tests to assess the risk of liver cancer.

Examinations are carried out among patients in risk groups:

• High risk group: viral hepatitis, liver cirrhosis of non-viral etiology (every 6 months);
• Very high risk group: cirrhosis of the liver of viral etiology (every 3 months).

Diagnosis of HCC consists of:

• Determination of the level of alpha-fetoprotein (AFP) every 3-6 months. (an increase in AFP up to 200 ng / ml or an increase in the l3-fraction of AFP up to 15% and above can serve as a sufficient basis for CT / MRI with contrast even with negative ultrasound)
• Ultrasound of the abdominal organs every 3-6 months

In case of detection of focal liver formation during ultrasound and / or an increase in the AFP level above 200 ng / ml, CT / MRI of the liver with bolus contrast enhancement is prescribed according to indications.

At the NROC, you can undergo high-quality diagnostics, get a "second opinion" about the type of tumor cells in the diagnosis, and, if necessary, immediately begin and receive qualified treatment.