Effect of Different Induction Immunosuppression on the Incidence of Infectious Complications after Kidney Transplantation-Single Center Study.

Background/Objectives: Potent immunosuppression lowers the incidence of acute graft rejection but increases the risk of infections. In order to decrease either infectious complications or acute rejection, it is necessary to identify risk groups of patients profiting from personalized induction immunosuppressive treatment. The aim of our analysis was to find whether there were higher incidences of infectious complications after kidney transplantation (KT) in groups with different induction immunosuppressive treatment and also to find independent risk factors for recurrent infections. Materials: We retrospectively evaluated all patients with induction treatment with basiliximab after kidney transplantation from 2014 to 2019 at our center relative to age- and sex-matched controls of patients with thymoglobulin induction immunosuppression. Results: Our study consisted of two groups: basiliximab (39) and thymoglobulin (39). In the thymoglobulin group we observed an increased incidence of recurrent infection in every observed interval; however, acute rejection was seen more often in the basiliximab group. A history of respiratory diseases and thrombocytopenia were identified as independent risk factors for recurrent bacterial infections from the first to sixth month after KT. Decreased eGFR from the first month, infections caused by multi-drug-resistant bacteria, and severe infections (reflected by the need for hospitalization) were identified as independent risk factors for recurrent bacterial infections from the first to the twelfth month after KT. Conclusions: We found that in the group of patients with thymoglobulin induction immunosuppressive treatment, infectious complications occurred significantly more often during the entire monitored period with decreased incidence of acute humoral and cellular rejection occurred more often.

Molecular Microscope Diagnostic System in Patients after Kidney Transplantation-First Experience.

BACKGROUND: The diagnosis of graft rejection relies on the identification of donor-specific antibodies along with histological findings. Borderline changes are particularly challenging, representing non-rejection findings in up to 70% of cases. The analysis aimed to compare the results of histopathological conclusions with the findings from examination using a molecular microscope, which assesses gene expression (whole-genome microarray chip technology). METHODS: Molecular microscope examination (MMDx) was applied to twelve patients (six men and six women) who underwent either indication or protocol graft biopsy. RESULTS: The average age of patients was 46.6 years ± 4.2 (average follow-up from kidney transplantation was 6.1 months ± 1.2). MMDx examination was performed during indication biopsy in 11 patients and protocol biopsy in 1 patient. A total of 33% of the findings matched and 50% did not. Finally, we present a case of a patient with acute cellular rejection findings without clinical and laboratory correlation, where the use of MMDx significantly altered the treatment strategy. CONCLUSIONS: MMDx examination is suitable for complementing patients with ambiguous histological findings and a clinical picture not corresponding to biopsy results. The limitations of MMDx include cost and its inability to evaluate the potential recurrence of the underlying kidney disease in the graft.

The role of hyperleptinaemia and low values of interleukin 10 in de novo DSA production after kidney transplantation.

BACKGROUND: White adipose tissue secretes a number of peptide hormones. The aim of this paper was to determine the role of leptin, adiponectin and interleukin-10 and interleukin-6 on the development of graft rejection in protocol biopsy after kidney transplantation. METHODS: In a prospective analysis (n = 104), we monitored the values of leptin, adiponectin, IL-6, and IL-10 prior to the transplantation and in the 3rd month after the transplantation. The protocol biopsy of the graft was performed in the 3rd month after the transplantation. The group was divided into the following according to the biopsy result: negative result, IFTA 1, borderline, and DSA positive. RESULTS: After adjusting for the differences in the baseline recipient and donor characteristics, we identified the hyperleptinaemia baseline (HR = 2.0444, P = 0.0341) and month 3 (HR = 49.8043, P < 0.0001) as independent risk factors for borderline changes in the protocol biopsy. The hyperleptinaemia baseline (HR = 7.4979, P = 0.0071) and month 3 (HR = 9.7432, P = 0.0057) are independent risk factors for de novo DSA positivity. A low value of IL-10 month 3 is a risk factor for de novo DSA positivity (HR = 3.0746, P = 0.0388). CONCLUSIONS: Higher leptin levels and low values of IL-10 might play a role in rejection and de novo DSA production.

Urinary tract infection in the context of mini-invasive procedures after kidney transplantation.

INTRODUCTION: The use of antibiotic prophylaxis in invasive procedures is generally accepted and highly recommended. The question is the need to apply antibiotic prophylaxis even in the case of mini-invasive procedures in the post-transplantation period. The aim of the study was to dermine the occurrence of infectious complications during mini-invasive procedures (pig-tail extraction, protocol biopsy) withou the use of antibiotic (ATB) prophylaxis. The secondary aim was to identify risk factors for a positive urine culture finding at the time of mini-invasive procedures. MATERIAL: This is a prospective monocentric study in which pacients after kidney transplantation at Transplantation centrum in Martin were included (n = 68). We investigated the incidence of positive urine findings at the time of pig-tail extraction (6 weeks after transplantation) and at the time of protocol biopsy (3 months after transplantation) with comparison within the group with and without ATB prophylaxis. RESULTS: Patients in group without ATB prophylaxis had a significantly higher tacrolimus value at the time of pig-tail extraction (p = 0.0274) and a significantly higher dose of mycophenolic acid at the time of protocol biopsy (p = 0.0429). We did not confirm significant difference in occcurence of positive urine findings at the time of pig-tail extraction or at the time of protocol biopsy. We completed a univariate logistic regression in order to identify a potential risk predictor for positive urine findings at the time of pig-tail extraction and protocol biopsy. None of the monitored parameters, including ATB prophylaxis, was confirmed as risk or protective factor. CONCLUSION: The use of antibiotic prophylaxis during mini-invasive procedures (pig-tail extraction, protocol biopsy) in the posttransplantation period had no effect on positive culture findings at our department. Based on our analysis, we therefore do not use antibiotic prophylaxis in the case of these procedures at our centre (Tab. 3, Fig. 6, Ref. 23).

Adiponectin/leptin ratio as a predictor of acute rejection in early post-transplant period in patients after kidney transplantation.

Introduction: Adipokines are largely involved in the regulation of immune system activity. While leptin is the main pro-inflammatory marker of adipose tissue, adiponectin is characterized by anti-inflammatory effects. The aim of our study was to determine the risk of acute graft rejection in protocol biopsy depending on the adiponectin/leptin (A/L) ratio in patients after kidney transplantation (KT). Materials and methods: A total of 104 patients were included in the prospective analysis, in whom the levels of adipokines were examined pre-transplant, in the 3rd month after KT and the A/L ratio was calculated. In the 3rd month after KT, all patients underwent protocol biopsy of the graft and examination of donor-specific antibodies (DSA) using the Luminex method. Results: After adjusting for differences in the basic characteristics of the donor and recipient, we identified a subgroup with A/L ratio < 0.5 pre-transplant [HR 1.6126, (P = 0.0133)] and 3 months after KT [HR 1.3150, (P = 0.0172)] as independent risk factor for acute graft rejection. In the subsequent specification of the rejection episode, we identified the risk ratio A/L < 0.5 before KT [HR 2.2353, (P = 0.0357)] and 3 months after KT [HR 3.0954, (P = 0.0237)] as independent risk factor for the development of acute humoral rejection with DSA positivity. Conclusion: This is the first study to investigate the relationship between A/L ratio and immunological risk in terms of the development of rejection changes in patients after KT. In our study, we found that A/L ratio < 0.5 is an independent risk factor for the development of acute humoral rejection and de novo DSA production in the third month after KT.

Gut microbiome and renal transplantation.

Gut microbiome research has been a surge of interest in many branches of medicine in the last decade. Our main aim is to show ability of microbes to infuence the functions of human body, especially in the immune system, and on the other hand to clarify changes in composition of gut microbiome in the post-transplantation period and their function for the long-term survival of the graft and the patient in the context of the occurrence of a wide range of complications. Kidney transplantation with the subsequent use of immunosuppressants and antibiotics affects the composition of gut microbiome. The subsequent development of dysbiosis significantly increases the risk of acute rejection, interstitial fibrosis and tubular atrophy of the graft, post-transplant diarrhoea, organ´s infections and metabolic complications such as post-transplant diabetes mellitus. Also important is the influence of the microorganisms of the gut microbiome on metabolism of immunosuppressants with the production of less effective components and the subsequent necessity of modifying their levels with a higher risk of underdosing and the occurrence of graft rejection. Support of the composition of the gut microbiome in the post-transplantation period in favor of bacteria producing short chain fatty acids (SCFA) is possible by changing of diet with predominance of fiber, the application of probiotics, prebiotics. According to available studies, it can lead to benefits in term of metabolic compensation, to the induction of donor-specific tolerance and many others, with an overall improvement in the quality of patient and graft survival.

Adiponectin/Leptin Ratio as an Index to Determine Metabolic Risk in Patients after Kidney Transplantation.

Background and Objectives: It has been confirmed that adiponectin/leptin (A/L) ratio correlates better with cardiometabolic risk factors than hormone levels alone. The aim of our study was to determine the risk of developing post-transplant diabetes mellitus (PTDM) and other metabolic conditions depending on A/L ratio after kidney transplantation (KT). Material and Methods: In a prospective analysis, the studied samples were divided into three groups: control group, prediabetes and PTDM group. Pre-transplantation, at 3, 6 and 12 months after KT, we recorded basic characteristics of donor and recipient. We also monitored levels of adipocytokines and calculated A/L ratio. Results: During observed period, we recorded significant increase in A/L ratio in control group (p = 0.0013), on the contrary, a significant decrease in PTDM group (p = 0.0003). Using Cox regression Hazard model, we identified age at time of KT (HR 2.8226, p = 0.0225), triglycerides at 1 year (HR 3.5735, p = 0.0174) and A/L ratio < 0.5 as independent risk factors for prediabetes and PTDM 1-year post-transplant (HR 3.1724, p = 0.0114). Conclusions: This is the first study to evaluate the relationship between A/L and risk of PTDM and associated metabolic states after KT. We found out that A/L ratio <0.5 is independent risk factor for prediabetes and PTDM 1 year post-transplant.

The impact of different induction immunosuppression protocols on patient survival, graft survival and acute graft rejection after kidney transplantation.

OBJECTIVES: The aim of the study was to stratify the immunological risk based on the presence of risk factors using different induction immunosuppressive protocols. BACKGROUND: The path to successful kidney transplantation reflects the accuracy of immunological risk assessment and choice of correct induction and maintenance of immunosuppression to avoid acute kidney rejection. METHODS: We performed a multicentre prospective analysis consisting of patients after kidney transplantation with a 12-month follow-up. RESULTS: In total, 152 kidney transplant recipients were included, of whom 100 were males (66.4 %). We divided patients according to the induction immunosuppression as follows: no induction (n = 19), induction with basiliximab (n = 60), and induction with ATG at cumulative doses of 3.5 mg/kg (n = 42) and 6 mg/kg (n = 31). In our study, we demonstrated a shorter survival of patients without induction immunosuppression. In the basiliximab group, the duration of dialysis ≥ 3 years (p = 0.0191), cold ischaemia time ≥ 1,020 minutes or expected delayed graft function (p < 0.0001) are independent risk factors for graft loss (p = 0.0097). CONCLUSIONS: Risk of no induction immunosuppression significantly exceeds the risks associated with its administration and is desirable even in patients at low immunological risk. Induction immunosuppression should be tailored individually and thus differ from patient to patient (Tab. 6, Fig. 1, Ref. 15).

Hyperleptinemia as a risk factor for post-transplant diabetes mellitus development after kidney transplantation.

INTRODUCTION: Adipose tissue is involved in the synthesis of hormones that have an impact on food intake regulation, control of insulin sensitivity or regulation of inflammatory processes. The aim of this study was to determine the importance of adipocytokines and interleukins levels for the development of post-transplant diabetes mellitus (PTDM) after kidney transplantation (KT). MATERIAL AND METHODS: In the prospective analysis, the studied sample (n = 104) was divided into the control group, prediabetes group and PTDM group. Prior to transplantation, and subsequently, at 3, 6 and 12 months after KT, we recorded the basic characteristics of the donor and recipient, including parameters reflecting graft function, metabolic and anthropometric parameters. At the same time, we monitored the levels of adiponectin, leptin and interleukins during the monitored period. RESULTS: Using multivariate logistic regression, we identified hyperleptinemia 12 months after KT as an independent risk factor for PTDM development 1 year after KT [OR 1.0320; 95% Cl 0.9785-1.0884 (p=0.0038)]. At the same time, we confirmed that age at the time of KT is also an independent risk factor for PTDM [OR 1.0903; 95% Cl 1.0149-1.1714 (p=0.0180)]. CONCLUSION: We confirmed that elevated leptin level 12 months after KT is associated with the development of PTDM (Tab. 3, Fig. 4, Ref. 22). Text in PDF www.elis.sk Keywords: adipocytokines, interleukins, post-transplant diabetes mellitus, kidney transplantation, leptin.

Age and sex disparity in infectious complications after kidney transplantation.

kidney transplantation (KT). BACKGROUND: Potent immunosuppression lowers the incidence of acute graft rejection but increases the risk of post-transplant infections. Older adults and females are at high risk of infections leading to poor outcome after KT. MATERIALS: Our analysis consisted of 66 males and 34 females after KT, average age 47.5±12.6 years. RESULTS: Female gender was a RF for the incidence of infection in general (p=0.0054), recurrent (p=0.0239), bacterial (p=0.0125) and mycotic infection (p=0.0103), recurrent bacterial infection (p=0.0258) 1st month after KT, RF for the incidence of infection in general (p=0.0218), bacterial (p=0.0186), mycotic (p=0.0318), recurrent (p=0.0216), recurrent bacterial infection (p=0.0368) from 1st to 6th month after KT and RF for the incidence of bacterial (p=0.0144), single (p=0.0355), recurrent (p=0.0007) and single bacterial infection (p=0.0309) 6 months after KT. Age >60 years was not found as a RF for the incidence of single, repeat infection regarding its aetiology. CONCLUSION: We found significant sex differences in the incidence of single and repeat infections in different time intervals after KT (Tab. 4, Fig. 3, Ref. 31).

Acute kidney rejection after anti-SARS-CoV-2 virus-vectored vaccine-case report.

COVID-19 infection remains a threat to the health systems of many countries. Potential success in the fight against the COVID-19 pandemic is the vaccination of high-risk groups, including patients with end-stage kidney disease (ESKD) and after solid organ transplantation (SOT). Immunosuppression in kidney transplant recipients can also reduce the immunogenicity of SARS-CoV-2 vaccines (varied by vaccine platform), available data suggest that they are efficacious in approximately 50-70%, compared to non-transplant situations. In this paper, we present a newly developed acute humoral and cellular rejection with acute allograft failure and need of hemodialysis 14 days after administration of the adenovirus vectored SARS-CoV-2 vaccine (AstraZeneca; CHADOx1, AZD1222). This occurred in a patient who previously had an asymptomatic COVID-19 infection. Case reports of acute allograft rejection after vaccination against SARS-CoV-2 can help stratify risk groups of patients who develop hyperimmune reactions. However, it is also possible that those with a previous mild primary COVID-19 infection may also develop acute allograft rejections upon COVID-19 re-infection.

Diagnostic hospitalizations before patient inclusion on the waiting list for kidney transplantation.

INTRODUCTION: For kidney transplantation is indicated any patient with chronic kidney disease in the terminal stage, unless it has a contraindication for this operation. The aim of this work is to evaluate the benefit of diagnostic hospitalizations of the patients before inclusion on the waiting list for kidney transplantation and to identify the most common differential diagnostic problems for the indication / contraindication for kidney transplantation. MATERIAL AND METHODS: This is a retrospective analysis, which included all potential recipients who underwent the examination process before inclusion on the waiting list and living donors in the form of diagnostic hospitalization at the Transplant Center at Martin University Hospital in 2016-2019. RESULTS: A total of 49 patients were included in the cohort, the average length of hospitalization was 5.6 days. Kidney trans plantation subsequently underwent 22 of these patients, 3 patients were clearly contraindicated.