Indices of Nutrition Status of Kidney and Pancreas Transplant Candidates.

Nutritional assessment is used to implement early nutritional interventions and reduce complications associated with malnutrition, which plays a crucial role in improving postoperative outcomes for patients undergoing pancreas and/or kidney transplantation. OBJECTIVE: The aim of this study was to analyze the nutritional status (NS) in patients eligible for kidney transplantation (KTx) and simultaneous kidney-pancreas transplantation (SPKTx). METHODS: We analyzed the database of hospitalized patients from 2020 to 2023 to identify preoperative parameters of NS in patients eligible for KTx and SPKTx. A total of 59 patients participated in the study, all of whom were candidates for KTx-23 or SPKTx-36. The study population consisted of 35 women (W) and 24 men (M), with an overall mean age of 44.8 ± 10.2 years (43.5 ± 10.2 years for W and 46.2 ± 10.9 years for M). Both groups included patients on hemodialysis (n = 34) and peritoneal dialysis (n = 12), and patients in the predialysis period (pre-emptive, n = 13). The examined parameters included Onodera's prognostic nutritional index (PNIO), the nutritional risk index (NRI), proper body mass calculated using the Lorenz formula, and the neutrophil-to-lymphocyte ratio (NLR). All patients were assessed according to the NRS 2002 scale. RESULTS: Analysis of the obtained results revealed that the NLR was only one differentiating parameter between Ktx and SPKtx group. Multivariate analysis adjusted for patients' age and gender, comparing quantitative NS indicators was performed. Albumin serum concentration was not dependent on patients' group (KTx/SPKTx) neither age nor gender P = .382. BMI was dependent on patients' age and gender, but not a group (KTx/SPKTx) P = .008. PNIO, NRI, and NRL were not dependent on patients' group (KTx/SPKTx) neither age nor gender. CONCLUSIONS: Additional effort should be devoted to the development of a proper nutrition plan for SPKTx a especially in peritoneal dialysis patients. Toward patients on the waiting list, the regular assessment of nutritional status should be performed which is not a rule in dialysis centers. SPKTx candidates in the perioperative period should receive proper nutrition taking into account their caloric and protein needs.

Immunolocalization of Matrix Metalloproteinases 2 and 9 and Their Inhibitors in the Hearts of Rats Treated with Immunosuppressive Drugs-An Artificial Intelligence-Based Digital Analysis.

BACKGROUND: Immunosuppressive agents represent a broad group of drugs, such as calcineurin inhibitors, mTOR inhibitors, and glucocorticosteroids, among others. These drugs are widely used in a number of conditions, but lifelong therapy is crucial in the case of organ recipients to prevent rejection. To further increase the safety and efficacy of these agents, their off-target mechanisms of action, as well as processes underlying the pathogenesis of adverse effects, need to be thoroughly investigated. The aim of this study was to examine the impact of various combinations of cyclosporine/tacrolimus/mycophenolate with rapamycin and steroids (CRG, TRG, MRG), on the morphology and morphometry of rats' cardiomyocytes, together with the presence of cardiac collagen and the immunoexpression of MMPs and TIMPs. METHODS: Twenty-four rats were divided into four groups receiving different immunosuppressive regiments. After six months of treatment, the hearts were collected and analyzed. RESULTS: Cardiomyocytes from the CRG cohorts demonstrated the most pronounced morphological alterations. In addition, chronic immunosuppression reduced the width and length of cardiac cells. However, immunosuppressive therapy did not alter the presence of cardiac collagen fibers. Nevertheless, we observed significant alterations regarding MMP/TIMP homeostasis. CONCLUSIONS: Chronic immunosuppression seems to disturb the MMP/TIMP balance in aspects of immunolocalization in the hearts of rats. Further studies are required to analyze other mechanisms and pathways affected by the use of immunosuppressants.

The Effects of Chronic Immunosuppressive Treatment on Morphological Changes in Cardiac Tissue and the Balance between Matrix Metalloproteinases (MMP-2 and MMP-9) and Their Inhibitors in the Rat Heart.

Using different three-drug immunosuppressive treatment regimens in a rat model, we aimed to determine the effects of long-term therapy on metalloproteinase-2 and metalloproteinase-9 activity and the expression of their inhibitors, as well as to assess the morphology of the animals' cardiac tissue. Our results suggest that chronic use of immunosuppressive drugs disrupts the balance between the activity of MMPs and TIMPs. Depending on the type of drug regimen used, this leads to abnormalities in the cardiac structure, collagen fiber accumulation, or cardiomyocyte hypertrophy. The information obtained in the present study allows us to conclude that the chronic treatment of rats with the most common clinical immunosuppressive regimens may contribute to abnormalities in the myocardial structure and function. The results presented in this study may serve as a prelude to more in-depth analyses and additional research into the optimal selection of an immunosuppressive treatment with the lowest possible risk of cardiovascular complications for patients receiving organ transplants.

Nutritional Risk of Candidates for Simultaneous Pancreatic-Kidney Transplantation-A Narrative Review.

INTRODUCTION: Not much is known about the significance of nutritional status and support in transplant surgery, least of all in simultaneous pancreatic and kidney transplantation. Malnutrition in the context of simultaneous pancreatic-kidney transplantation seems to be complex and a still poorly investigated problem. Since SPKTX is highly qualified and also has a small volume procedure, it is difficult to obtain data from large cohorts of patients. The aim of this article is to gather existing evidence and information about the subject, as well as to elicit some questions and goals for the future. METHODS: We searched through the Pub-Med database using the keywords "pancreas and kidney transplantation" combined with "nutritional risk", "nutritional status", "malnutrition", "nutritional intervention", and "frailty", finding a total of 4103 matching results. We then narrowed it down to articles written in English with the full text available. We also researched through the references of articles most accurately matching our researched terms. RESULTS: There are numerous tools that have been investigated for the screening of malnutrition, such as the NRI index, PNI index, NLR, SGA scale, and NRS-2002 scale, each of which proved to be of some use in predicting patient outcomes in different surgical settings. Since all of them differed in components and assessed parameters and, in the absence of more sensitive or infallible indicators, the most reasonable approach seems to evaluate them jointly. CONCLUSION: It is important to underline the necessity of nutritional screening and the subsequent introduction of adequate therapy while awaiting transplantation in an attempt to improve results. Considering the complexity of surgical procedures and the severity of underlying diseases with their intense metabolic components, the patient's nutritional status seems to significantly influence results. Consequently, nutritional risk assessments should be a part of the routine care of patients qualified for transplantation.

The long-term effects of multidrug immunosuppressive protocols based on calcineurin inhibitors and conversion to rapamycin on the morphology, apoptosis, and proliferation of rat salivary glands.

BACKGROUND: The effect of multidrug immunosuppressive protocols on the salivary glands is still unknown. This study aimed to determine the influence of immunosuppressive regimens based on calcineurin inhibitors (CNIs) and conversion to rapamycin on the morphology, apoptosis, and proliferation of rat salivary glands. METHODS: Male rats received cyclosporin A (CsA), tacrolimus (FK-506), mycophenolate mofetil (MMF), rapamycin (Rapa), and prednisone (Pre) according to three-drug protocols: CMP (CsA, MMF, and Pre), CMP/R (CsA, MMF, and Pre with conversion to Rapa), TMP (FK-506, MMF, and Pre), and TMP/R (FK-506, MMF, and Pre with conversion to Rapa). Morphological and immunohistochemical and quantitative analyses of the salivary glands were performed. RESULTS: Structural changes in salivary glands were observed in all experimental groups, especially in the submandibular gland. In the salivary glands, the percentages of collagen fibers and TUNEL-, Ki67- and PCNA-positive cells were higher in the experimental groups vs. the control but were lower in the CMP/R and TMP/R groups vs. the CMP and TMP groups, with the exception of collagen fibers in the parotid gland in the TMP/R group vs. the TMP group. CONCLUSIONS: Long-term administration of CNIs in triple regimens and after conversion to rapamycin monotherapy, causes morphological changes in the salivary glands of rats. Immunosuppressive treatment based on CNIs is associated with an increase in collagen accumulation. The effects of the conversion of treatment with CNIs to rapamycin in immunosuppressive protocols in rat salivary glands lead to decreased fibrosis, apoptosis, and proliferation. These changes may possibly prevent abnormalities resulting from the application of CNIs.

The Effect of Calcineurin Inhibitors on MMPs Activity in Heart and Their Side Effects-A Review of Literature.

This review focuses on the role of metalloproteinases in the pathogenesis of myocardial injury in various disease entities. It reveals how the expression and serum levels of metalloproteinases and their inhibitors change in many disease states. At the same time, the study offers a review of the impact of immunosuppressive treatment on this relationship. Modern immunosuppressive treatment is based mainly on the use of calcineurin inhibitors, including cyclosporine A and tacrolimus. The use of these drugs may carry a number of side effects, specifically to the cardiovascular system. The scale and degree of long-term influence on the organism remains unclear, but a significant risk of complications for transplant recipients who take immunosuppressive drugs as part of their daily treatment is to be expected. Therefore, the knowledge on this subject should be expanded and the negative effects of post-transplant therapy minimized. Immunosuppressive therapy plays an important role in the expression and activation of tissue metalloproteinases and their specific inhibitors, which leads to many tissue changes. The presented study is a collection of research results on the effects of calcineurin inhibitors on the heart, with particular emphasis placed on the participation of MMP-2 and MMP-9. It is also an analysis of the effects of specific heart diseases on myocardial remodeling through inductive or inhibitory effects on matrix metalloproteinases and their inhibitors.

Demand for Water-Soluble Vitamins in a Group of Patients with CKD versus Interventions and Supplementation-A Systematic Review.

BACKGROUND: Increasingly, chronic kidney disease (CKD) is becoming an inevitable consequence of obesity, metabolic syndrome, and diabetes. As the disease progresses, and through dialysis, the need for and loss of water-soluble vitamins both increase. This review article looks at the benefits and possible risks of supplementing these vitamins with the treatment of CKD. METHODS: Data in the PubMed and Embase databases were analyzed. The keywords "chronic kidney disease", in various combinations, are associated with thiamin, riboflavin, pyridoxine, pantothenic acid, folates, niacin, cobalamin, and vitamin C. This review focuses on the possible use of water-soluble vitamin supplementation to improve pharmacological responses and the overall clinical condition of patients. RESULTS: The mechanism of supportive supplementation is based on reducing oxidative stress, covering the increased demand and losses resulting from the treatment method. In the initial period of failure (G2-G3a), it does not require intervention, but later, especially in the case of inadequate nutrition, the inclusion of supplementation with folate and cobalamin may bring benefits. Such supplementation seems to be a necessity in patients with stage G4 or G5 (uremia). Conversely, the inclusion of additional B6 supplementation to reduce CV risk may be considered. At stage 3b and beyond (stages 4-5), the inclusion of niacin at a dose of 400-1000 mg, depending on the patient's tolerance, is required to lower the phosphate level. The inclusion of supplementation with thiamine and other water-soluble vitamins, especially in peritoneal dialysis and hemodialysis patients, is necessary for reducing dialysis losses. Allowing hemodialysis patients to take low doses of oral vitamin C effectively reduces erythropoietin dose requirements and improves anemia in functional iron-deficient patients. However, it should be considered that doses of B vitamins that are several times higher than the recommended dietary allowance of consumption may exacerbate left ventricular diastolic dysfunction in CKD patients. CONCLUSIONS: Taking into account the research conducted so far, it seems that the use of vitamin supplementation in CKD patients may have a positive impact on the treatment process and maintaining a disease-free condition.

The Effect of Chronic Immunosuppressive Regimens Treatment on Aortal Media Morphology and the Balance between Matrix Metalloproteinases (mmp-2 and mmp-9) and Their Inhibitors in the Abdominal Aorta of Rats.

Immunosuppressive drugs are widely and chronically used to avoid graft rejection in transplant recipients. However, they are also known to have organotoxic effects and can exert numerous side effects. The aim of this study was to assess whether the chronic treatment of rats with the most commonly used clinical immunosuppressive regimens in organ recipients had an effect on the morphology and function of the aorta. The rats were divided into five groups and each group was chronically treated with different sets of three immunosuppressive drugs (TRG, CRG, MRG, CMG, TMG) for 6 months. The changes were most profound in calcineurin inhibitor-based protocols. TMG protocol treatment was characterized by the most numerous alterations such as morphological changes, changes in the thickness of the tunic media, wider distances between elastic lamellae, an increase in the number of vSMCs and changes in collagen deposition. We concluded that the morphological changes were connected with MMP-2 and MMP-9/TIMP-2 and TIMP-1 imbalances, which was also determined and noticed.

Impact of COVID-19 on pancreatic cancer surgery: A high-volume Polish center experience.

BACKGROUND: A total of 148 surgeries were performed in our center on patients with pancreatic cancer in 2020. In 2019, 263 such procedures were performed (77.7% more) in this facility. OBJECTIVES: To analyze the impact of coronavirus disease 2019 (COVID-19) on pancreatic cancer surgery type, number and outcome in our center. MATERIAL AND METHODS: Retrospective data analysis of medical documentation in a hospital database from January 2019 till December 2020. RESULTS: In 2020, we observed an increase of tumors localized in the tail of the pancreas (P) - 29 cases (19.9%) in 2020 compared to 26 cases (9.9%) in 2019 (p = 0.005). In 2020, our patients presented with much greater advancement of the disease illustrated by the increased tumor size (median 3.5 cm in 2020 compared to 3.0 cm in 2019), although it did not reach statistical significance (p = 0.073). In 2020, we performed more palliative procedures, e.g., bypassing anastomoses (17 (11.6%) in 2020 compared to 8 (3%) in 2019 (p < 0.001)), more open biopsies of P (21 (14.4%) in 2020 compared to 21 (7.9%) in 2019 (p = 0.041)), and more percutaneous biopsies of P (7 (4.8%) in 2020 and 0 in 2019 (p = 0.001)). We observed a significant decrease in the number of Whipple procedures (53 (36.3%) in 2020 and 125 (47.5%) in 2019 (p = 0.037)). The most common histopathological finding was adenocarcinoma of the P, accounting for 50% in 2020 and almost 52% of all tumor cases in 2019. In a group of 148 patients operated on due to a P tumor during the COVID-19 pandemic, only 6 patients died, which resulted in a mortality rate of 4.1% compared to 13.4% mortality rate in 2019 (34 deaths/263 patients; p = 0.005). We observed less leakage of gastrointestinal anastomosis (0/148 in 2020 and 10/263 in 2019 (p = 0.038)). CONCLUSIONS: Particular attention should be paid to patients with an aggressive type of cancer who have completed neoadjuvant therapy, as they are unable to undergo other therapeutic options. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive cancer patients should be postponed until recovery. Relatively few postoperative complications and low all-cause mortality are the result of a more careful selection of oncological patients before the admission to the surgical ward, as well as a ompliance with the principles of planning the procedure and organization of the operating theater during the COVID-19 pandemic.

Urinary Tract Virome as an Urgent Target for Metagenomics.

Virome-a part of a microbiome-is a term used to describe all viruses found in the specific organism or system. Recently, as new technologies emerged, it has been confirmed that kidneys and the lower urinary tract are colonized not only by the previously described viruses, but also completely novel species. Viruses can be both pathogenic and protective, as they often carry important virulence factors, while at the same time represent anti-inflammatory functions. This paper aims to show and compare the viral species detected in various, specific clinical conditions. Because of the unique characteristics of viruses, new sequencing techniques and databases had to be developed to conduct research on the urinary virome. The dynamic development of research on the human microbiome suggests that the detailed studies on the urinary system virome will provide answers to many questions about the risk factors for civilization, cancer, and autoimmune diseases.

The Course of SARS-CoV-2 in a Patient After a Recent Kidney Transplant: A Literature Review on COVID-19 Therapy.

BACKGROUND: Kidney transplant recipients are at high risk of severe complications and death due to coronavirus disease 2019 (COVID-19). METHODS: The first part of the article describes a case of COVID-19 in our patient after a recent kidney transplant. The second part of the article presents the outcome of literature search from multiple resources from April 2020 until March 2021. Abstracts were screened, followed by full-text review with data extraction. Part 2 discusses current treatment options of COVID-19, and part 3 refers to this treatment application in patients after solid organ transplant. RESULTS: We have summarized 45 studies from China, France, Italy, Spain, the United Kingdom, and the United States. Mortality rates from published studies were variable. Based on early data from Spain, 42% of patients who developed COVID-19 within 60 days of transplant died. According to results of the European Renal Association COVID-19 Database collaboration group, the 28-day COVID-19-related mortality is 21.3% for kidney transplant recipients, which is still markedly higher than what is observed in other populations. Acute kidney injury was common, and mycophenolate mofetil and mammalian target of rapamycin were discontinued in most patients. CONCLUSIONS: Effective therapy has been sought since the outbreak of the pandemic, and at the same time intensive work has been done to produce a vaccine that could effectively protect against the disease. Summing up the efforts of numerous groups of researchers from around the world that have been continued since the beginning of 2020, we may assume the following: (1) we still do not have causal drugs that would reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and allow its complete elimination, but antispike monoclonal antibodies against SARS-CoV-2 seem to be very promising, and (2) the withdrawal of antiproliferative and antimetabolic drugs and the continuation of steroids and calcineurin inhibitors is now a commonly accepted approach in patients after organ transplant.

The Effect of Immunosuppressive Drugs on MMPs Activity in The Walls of Blood Vessels - A Systematic Review.

The current study focuses on the role of MMPs in the pathogenesis of the vascular damage and at the same time it offers the review referring to the influence of the immunosuppressive treatment on this interdependence. Contemporary immunosuppressive treatment constitutes of four groups of medications, such as: calcineurin inhibitors including cyclosporine A and tacrolimus; inhibitors of the inosine monophosphate dehydrogenase - the only agent from this group currently used in transplantation is mycophenalate mofetil (MMF); mTOR inhibitors, consisting of everolimus and glucocorticosteroids. Due to the fact that the properties of immunosuppressive drugs still remain unclear and transplant recipients need to use these medicines every day, knowledge of this should be further expanded. The deceases of the patients with the functioning graft who were diagnosed with the cardiovascular system diseases, constitute 50% of all renal transplant recipients. Immunosuppressive treatment leads to many pathological alterations within the organs and tissues and additionally they undoubtedly affect the activity of MMPs in the wall of the vessels.

The long-term effects of rapamycin-based immunosuppressive protocols on the expression of renal aquaporins 1, 2, 3 and 4 water channels in rats.

BACKGROUND: To this day, the effect of multi-drug immunosuppressive protocols on renal expression of AQPs is unknown. This study aimed to determine the influence of rapamycin-based multi-drug immunosuppressive regimens on the expression of aquaporins (AQPs) 1, 2, 3, and 4 in the rat kidney. METHODS: For 6 months, 24 male Wistar rats were administered immunosuppressants, according to the three-drug protocols used in patients after organ transplantation. The rats were divided into four groups: the control group, the TRP group (tacrolimus, rapamycin, prednisone), the CRP group (cyclosporine A, rapamycin, prednisone), and the MRP group (mycophenolate mofetil, rapamycin, prednisone). Selected red cell indices and total calcium were measured in the blood of rats and quantitative analysis of AQP1, AQP2, AQP3 and AQP4 immunoexpression in the kidneys were performed. RESULTS: In the TRP and CRP groups, a mild increase of mean corpuscular hemoglobin concentration, hematocrit and total calcium were observed. Moreover, decreased expression of AQP1-4 was found in all experimental groups, with the highest decrease in the CRP group. CONCLUSIONS: The long-term immunosuppressive treatment using multi-drug protocols decreased AQP1-4 expressions in renal tubules, possibly leading to impaired urine-concentrating ability in rat.

The Effects of Long-Term Immunosuppressive Therapies on the Structure of the Rat Prostate.

Background: Little is known about the overall impact of immunosuppressive drugs on the prostate. The study aimed to determine the impact of different protocols of immunosuppressive treatment on the structure of the rat ventral prostate. Methods: For 6 months, 48 male Wistar rats received immunosuppressive drugs: cyclosporin A, tacrolimus, mycophenolate mofetil, rapamycin, and prednisone, according to three-drug protocols. Light and transmission electron microscopic studies, and quantitative evaluation of immunohistochemical expression of selected intermediate filaments, CD117+ mast cells, and CD138+ plasma cells were performed in the rat ventral prostate. Results: In all experimental groups, acini focal hyperplasia, changes to the ultrastructure of the glandular epithelium, changes in the expression of cytokeratins and desmin, and numerous mast and plasma cells in the prostate stroma were found. In cyclosporine-A-based groups, atrophy and numerous intracellular vacuoles were observed. In groups where a three-drug treatment was replaced with rapamycin, morphological alterations were less severe compared to those without conversion. Conclusions: In the rat ventral prostate, (1) immunosuppressive protocols affect the morphology and immunohistochemical expression of intermediate filaments, (2) morphological alterations, expression, and localization of selected proteins are not connected with adenocarcinoma development, and (3) conversion of the treatment to rapamycin may prevent hyperplastic abnormalities.

Prevalence of Human Papillomavirus Infection in the Head and Neck Area of Patients After Kidney Transplantation Treated With Immunosuppressive Therapy.

The introduction of new and stronger immunosuppressive agents has significantly improved the overall survival rate of patients with transplanted organs; however, prolonged use of immunosuppressive agents has led to severe complications, such as the development of de novo malignant cancers. The incidence of malignant tumors is 3 to 5 times greater among renal transplant recipients than that of the overall population. Traditional neoplasms of the head and neck region are associated with the addiction to smoking and drinking alcohol. However, recent studies indicate that cancers of the throat, tongue, and tonsils are primarily associated with the human papillomavirus (HPV) infection. At present, approximately 25% of the head and neck squamous cell carcinomas are associated with HPV infection. Therefore, we aimed to determine the incidence of oropharyngeal HPV infection in recipients with kidney transplants treated with immunosuppressive therapy and to determine the factors that may favor the contraction of infectious diseases. Furthermore, we considered the purpose of vaccination against HPV among transplant recipients. A total of 32 recipients with kidney transplants were included in this study. Medical history was obtained and a throat swab was collected from each patient. The presence of the HPV DNA in the throat was determined using the GP5+/GP6+ primers. According to our results, 28% of the recipients with kidney transplants were positive for oropharyngeal HPV infection. In addition, among the investigated risk factors, early commencement of the sexual life (below the age of 16 years) was significantly correlated with the development of oropharyngeal HPV infection.

The Comparison of Parameters of Oxidative Stress in Native Rat Livers Between Different Immunosuppressive Regimens.

BACKGROUND It is thought that immunosuppressive treatment, besides anti-rejection properties, leads to pathological changes within the organ due to activation of mechanisms associated with oxidative stress. The aim of this study was to examine the parameters of oxidative stress in the livers of rats treated with the most commonly used transplant recipient drug regimens. MATERIAL AND METHODS The rat livers were obtained from archival material obtained from the previously performed experiment. Malondialdehyde (MDA), reduced glutathione (GSH) concentrations, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were analyzed. RESULTS Only the group treated with tacrolimus (T), mycophenolate mofetil (M), and prednisone (P), the TMP group, showed a slight increase in lipid peroxide concentration compared to the control group, though the difference was not statistically significant. Comparison of lipid peroxide concentration between the other treatment combinations and the control group showed a significant decrease. Additionally, a difference in lipid peroxide concentrations in the livers was observed between the cyclosporine A (C) group and tacrolimus (T) group. Alterations of other oxidative stress parameters were also observed in different regimens. CONCLUSIONS Long-lasting immunosuppressive treatment does indeed affect redox status; however, the antioxidant defenses of the liver against the effects of excess hydrogen peroxide are efficient, so the superoxide dismutase/glutathione peroxidase (SOD/GPx) and superoxide dismutase/catalase (SOD/CAT) ratios were not significant.

Correlation Between Stem and Progenitor Cells Number and Immune Response in Patients After Allogeneic Kidney Transplant.

BACKGROUND Stem and progenitor cells are of great interest in all medical procedures involving tissue regeneration. There is a consensus that the use of stem cells after solid organ transplantation may play a role in tissue repair and in immunosuppression. The aim of this study was to determine possible relations between stem cell count and the immune response in a group of patients after kidney transplantation. MATERIAL AND METHODS The study was conducted on a group of 100 patients who underwent kidney transplantation. The following phenotypic markers of the studied cell subpopulations were adopted: Treg cells (CD3+CD4+CD25high), circulating hematopoietic cells (CD34+CD133+CD45+CD38-), and non-hematopoietic cells (Lin-CXCR4+CD133-CD45-). Cell subpopulations were assessed using LSRII flow cytometer (BD Biosciences, San Jose, CA, USA). RESULTS Positive correlation was observed between non-hematopoietic stem cells percentage and recipient's platelets count (P=0.04). Moreover, a higher percentage of non-hematopoietic cells was accompanied by lower numbers of B lymphocytes (P=0.03) and Treg cells (P=0.02). CONCLUSIONS Our study revealed significant associations between the intensity of ongoing immune response processes and tissue damage, and the release of stem and progenitor cells into circulation. These findings suggest their role in the stimulation of protective processes in terms of graft regeneration.

Effect of long-term immunosuppressive therapy on native rat liver morphology and hepatocyte- apoptosis.

A negative result of therapy based on immunosuppressive drugs is its leading to pathological alterations in the organ, including liver. Use of immunosuppressive medication may also lead to organized and genetically controlled cell death - apoptosis. The aim of this study was to examine histopathological changes in the livers of rats treated with immunosuppressive drugs, and also to determine the effects of different groups of immunosuppressive drugs on apoptosis activity in the hepatocytes of rat livers. The study was conducted on archival material obtained from Department of Nephrology, Transplantology and Internal Medicine of the Independent Public Clinical Hospital No. 2 at the Pomeranian Medical University in Szczecin, Poland. Statistical comparison of the treatment groups showed that all groups with rapamycin (sirolimus)-based regimens: Tacrolimus, Rapamycin, Glucocorticosteroid (TRG); Cyclosporine, Rapamycin, Glucocorticosteroid (CRG); Mycophenolate, Rapamycin, Glucocorticosteroid (MRG) and additionally Cyclosporine, Mycophenolate, Glucocorticosteroid (CMG) exhibited significantly more pronounced apoptosis than the control group, with p < 0.01, p < 0.05, p < 0.01 and p < 0.01, respectively. Furthermore, in the TRG group, over 90% of apoptotic hepatocytes were seen in the examined classic lobules. Additionally, every liver from treatment group was pathologically altered, including dilated sinusoids, pyknotic nuclei, swollen walls of the vessels. Long-lasting immunosuppressive treatment affects the liver both in terms of histological changes within the structure of the liver and in terms of the percentage of apoptotic hepatocytes. The following study seems to be very innovating due to the duration of the experiment and used drugs-protocols, since they reflect human treatment.