scholarly journals Lymphocytes as an Indicator for Initial Kidney Function: A Single Center Analysis of Outcome after Alemtuzumab or Basiliximab Induction

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Annemarie Weissenbacher ◽  
Theresa Hautz ◽  
Michael Kimelman ◽  
Rupert Oberhuber ◽  
Hanno Ulmer ◽  
...  
Keyword(s):  
Kidney Function ◽  
Induction Therapy ◽  
Clinical Course ◽  
Graft Function ◽  
Control Group ◽  
Single Center ◽  
Lymphocyte Depletion ◽  
Recipient Age ◽  
Kidney Transplantations ◽  
And Function

Alemtuzumab, an anti-CD52 T-cell and B-cell depleting monoclonal antibody, is established for induction therapy in renal transplantation (KTx). We herein provide a comparative analysis between alemtuzumab and basiliximab induction therapy and correlate lymphocyte depletion and recovery with the clinical course after KTx. This is a single center retrospective analysis of 225 patients/consecutive kidney transplantations treated with alemtuzumab for lymphocyte depletion and 205 recipients treated with basiliximab. Mean lymphocyte counts were 22.8 ± 9.41% before Tx and 2.61 ± 3.11% between week 1 and week 3 in the alemtuzumab group and 23.77 ± 10.42% before Tx and 13.92 ± 8.20% in the basiliximab group. Delayed graft function (DGF), cytomegalovirus (CMV) status, and recipient age showed a significant correlation with lymphocyte counts in the alemtuzumab group only. The outcome was read in reference to the velocity of lymphocyte recovery and in comparison to the control group. Lymphocyte counts early after transplantation, following alemtuzumab treatment, could be identified as a predictive factor for kidney function early after transplantation. A detailed analysis of phenotype and function of lymphocytes after alemtuzumab induction together with a correlation with the clinical course is warranted.

scholarly journals Combined low-dose everolimus and low-dose tacrolimus after Alemtuzumab induction therapy: a randomized prospective trial in lung transplantation

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alberto Benazzo ◽  
Ara Cho ◽  
Anna Nechay ◽  
Stefan Schwarz ◽  
Florian Frommlet ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Lung Transplantation ◽  
Kidney Function ◽  
Induction Therapy ◽  
Low Dose ◽  
Prospective Trial ◽  
Control Group ◽  
Long Term Outcomes ◽  
Maintenance Immunosuppression

Abstract Background Long-term outcomes of lung transplantation are severely affected by comorbidities and development of chronic rejection. Among the comorbidities, kidney insufficiency is one of the most frequent and it is mainly caused by the cumulative effect of calcineurin inhibitors (CNIs). Currently, the most used immunosuppression protocols worldwide include induction therapy and a triple-drug maintenance immunosuppression, with one calcineurin inhibitor, one anti-proliferative drug, and steroids. Our center has pioneered the use of alemtuzumab as induction therapy, showing promising results in terms of short- and long-term outcomes. The use of alemtuzumab followed by a low-dose double drug maintenance immunosuppression, in fact, led to better kidney function along with excellent results in terms of acute rejection, chronic lung allograft dysfunction, and survival (Benazzo et al., PLoS One 14(1):e0210443, 2019). The hypothesis driving the proposed clinical trial is that de novo introduction of low-dose everolimus early after transplantation could further improve kidney function via a further reduction of tacrolimus. Based on evidences from kidney transplantation, moreover, alemtuzumab induction therapy followed by a low-dose everolimus and low-dose tacrolimus may have a permissive action on regulatory immune cells thus stimulating allograft acceptance. Methods A randomized prospective clinical trial has been set up to answer the research hypothesis. One hundred ten patients will be randomized in two groups. Treatment group will receive the new maintenance immunosuppression protocol based on low-dose tacrolimus and low-dose everolimus and the control group will receive our standard immunosuppression protocol. Both groups will receive alemtuzumab induction therapy. The primary endpoint of the study is to analyze the effect of the new low-dose immunosuppression protocol on kidney function in terms of eGFR change. The study will have a duration of 24 months from the time of randomization. Immunomodulatory status of the patients will be assessed with flow cytometry and gene expression analysis. Discussion For the first time in the field of lung transplantation, this trial proposes the combined use of significantly reduced tacrolimus and everolimus after alemtuzumab induction. The new protocol may have a twofold advantage: (1) further reduction of nephrotoxic tacrolimus and (2) permissive influence on regulatory cells development with further reduction of rejection episodes. Trial registration EUDRACT Nr 2018-001680-24. Registered on 15 May 2018

scholarly journals Hypothermic Oxygenated Perfusion Versus Static Cold Storage for Expanded Criteria Donors in Liver and Kidney Transplantation: Protocol for a Single-Center Randomized Controlled Trial

10.2196/13922 ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. e13922
Author(s):  
Matteo Ravaioli ◽  
Lorenzo Maroni ◽  
Andrea Angeletti ◽  
Guido Fallani ◽  
Vanessa De Pace ◽  
...  
Keyword(s):  
Cold Storage ◽  
Controlled Trial ◽  
Graft Function ◽  
Control Group ◽  
Organ Shortage ◽  
Single Center ◽  
Graft Dysfunction ◽  
Open Label ◽  
Preservation Method ◽  
Liver And Kidney

Background Extended criteria donors (ECD) are widely utilized due to organ shortage, but they may increase the risk of graft dysfunction and poorer outcomes. Hypothermic oxygenated perfusion (HOPE) is a recent organ preservation strategy for marginal kidney and liver grafts, allowing a redirect from anaerobic metabolism to aerobic metabolism under hypothermic conditions and protecting grafts from oxidative species–related damage. These mechanisms may improve graft function and survival. Objective With this study, we will evaluate the benefit of end-ischemic HOPE on ECD grafts for livers and kidneys as compared to static cold storage (SCS). The aim of the study is to demonstrate the ability of HOPE to improve graft function and postoperative outcomes of ECD kidney and liver recipients. Methods This is an open-label, single-center randomized clinical trial with the aim of comparing HOPE with SCS in ECD kidney and liver transplantation. In the study protocol, which has been approved by the ethics committee, 220 patients (110 liver recipients and 110 kidney recipients) will be enrolled. Livers and kidneys assigned to the HOPE group undergo machine perfusion with cold Belzer solution (4-10°C) and continuous oxygenation (partial pressure of oxygen of 500-600 mm Hg). In the control group, livers and kidneys undergoing SCS are steeped in Celsior solution and stored on ice. Using the same perfusion machine for both liver and kidney grafts, organs are perfused from the start of the back-table procedure until implantation, without increasing the cold ischemia time. For each group, we will evaluate clinical outcomes, graft function tests, histologic findings, perfusate, and the number of allocated organs. Publication of the results is expected to begin in 2021. Results Dynamic preservation methods for organs from high-risk donors should improve graft dysfunction after transplantation. To date, we have recruited 108 participants. The study is ongoing, and recruitment of participants will continue until January 2020. Conclusions The proposed preservation method should improve ECD graft function and consequently the postoperative patient outcomes. Trial Registration ClinicalTrials.gov NCT03837197; https://clinicaltrials.gov/ct2/show/NCT03837197 ; Archived by WebCite® at http://www.webcitation.org/76fSutT3R International Registered Report Identifier (IRRID) DERR1-10.2196/13922

Does Cerebral Angiography of Cadaveric Kidney Donors Interfere with Graft Function?

1987 ◽  
Vol 28 (4) ◽  
pp. 451-455 ◽  
Author(s):  
H. Weibull ◽  
C. Cederholm ◽  
T. Almén ◽  
D. Bergqvist ◽  
R. Takolander ◽  
...  
Keyword(s):  
Contrast Media ◽  
Graft Survival ◽  
Cerebral Angiography ◽  
Graft Function ◽  
Control Group ◽  
Kidney Donors ◽  
Animal Data ◽  
Renal Grafts ◽  
Cadaveric Kidney ◽  
And Function

Cerebral angiography is used to diagnose brain death of cadaver kidney donors. Clinical and animal data suggest that angiographic contrast media may potentiate the noxious effect of renal ischemia. In order to find out if cerebral angiography of cadaveric kidney donors prior to nephrectomy interferes with function or survival of the renal grafts, two groups of cadaveric donors were compared. One group had been exposed to contrast medium from cerebral angiography in median 18 hours before nephrectomy and the other had not. There was no difference in graft survival and function between the two groups. In a previous investigation angiography was performed two hours before explantation and in that investigation there was a shorter graft survival in the angiography group than in a control group. A delay of 12 hours is suggested between cerebral angiography and explantation, to decrease the combined harmful effects of contrast media and ischemia on renal grafts.

scholarly journals Hypothermic Oxygenated Perfusion Versus Static Cold Storage for Expanded Criteria Donors in Liver and Kidney Transplantation: Protocol for a Single-Center Randomized Controlled Trial (Preprint)

2019 ◽  
Author(s):  
Matteo Ravaioli ◽  
Lorenzo Maroni ◽  
Andrea Angeletti ◽  
Guido Fallani ◽  
Vanessa De Pace ◽  
...  
Keyword(s):  
Cold Storage ◽  
Controlled Trial ◽  
Graft Function ◽  
Control Group ◽  
Organ Shortage ◽  
Single Center ◽  
Graft Dysfunction ◽  
Open Label ◽  
Preservation Method ◽  
Liver And Kidney

BACKGROUND Extended criteria donors (ECD) are widely utilized due to organ shortage, but they may increase the risk of graft dysfunction and poorer outcomes. Hypothermic oxygenated perfusion (HOPE) is a recent organ preservation strategy for marginal kidney and liver grafts, allowing a redirect from anaerobic metabolism to aerobic metabolism under hypothermic conditions and protecting grafts from oxidative species–related damage. These mechanisms may improve graft function and survival. OBJECTIVE With this study, we will evaluate the benefit of end-ischemic HOPE on ECD grafts for livers and kidneys as compared to static cold storage (SCS). The aim of the study is to demonstrate the ability of HOPE to improve graft function and postoperative outcomes of ECD kidney and liver recipients. METHODS This is an open-label, single-center randomized clinical trial with the aim of comparing HOPE with SCS in ECD kidney and liver transplantation. In the study protocol, which has been approved by the ethics committee, 220 patients (110 liver recipients and 110 kidney recipients) will be enrolled. Livers and kidneys assigned to the HOPE group undergo machine perfusion with cold Belzer solution (4-10°C) and continuous oxygenation (partial pressure of oxygen of 500-600 mm Hg). In the control group, livers and kidneys undergoing SCS are steeped in Celsior solution and stored on ice. Using the same perfusion machine for both liver and kidney grafts, organs are perfused from the start of the back-table procedure until implantation, without increasing the cold ischemia time. For each group, we will evaluate clinical outcomes, graft function tests, histologic findings, perfusate, and the number of allocated organs. Publication of the results is expected to begin in 2021. RESULTS Dynamic preservation methods for organs from high-risk donors should improve graft dysfunction after transplantation. To date, we have recruited 108 participants. The study is ongoing, and recruitment of participants will continue until January 2020. CONCLUSIONS The proposed preservation method should improve ECD graft function and consequently the postoperative patient outcomes. CLINICALTRIAL ClinicalTrials.gov NCT03837197; https://clinicaltrials.gov/ct2/show/NCT03837197 ; Archived by WebCite® at http://www.webcitation.org/76fSutT3R INTERNATIONAL REGISTERED REPORT DERR1-10.2196/13922

scholarly journals Modest dose anti-thymocyte globulin administered intraoperatively is safe and effective in kidney transplantations: a retrospective study

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7274 ◽  
Author(s):  
Hui-Ying Liu ◽  
Yuan-Tso Cheng ◽  
Hao Lun Luo ◽  
Chiang-Chi Huang ◽  
Chien Hsu Chen ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Induction Therapy ◽  
Dose Regimen ◽  
Low Dose ◽  
Graft Loss ◽  
Graft Function ◽  
Calcineurin Inhibitors ◽  
Kidney Transplant Recipients ◽  
Significant Difference ◽  
Kidney Transplantations

Background Anti-thymocyte globulin (ATG) as induction therapy in renal transplantation is facing the dilemma of reducing the incidence of acute rejection (AR) and delayed graft function (DGF) or increasing risks of infection and malignancy. The purpose of this study was to delineate the safety and efficiency of the optimal ATG dosage. Methods We retrospectively evaluated 91 deceased donor kidney transplant recipients (KTRs) in our institution between March 2011 and January 2019. The patients were classified into three groups based on induction therapy: (1) Group 1: modest-dose ATG (three mg/kg) intraoperatively (N = 21); (2) Group 2: low-dose ATG (1–1.5 mg/kg) intraoperatively (N = 23); (3) Group 3: basiliximab 20 mg both on day 0 and 4 (N = 47). In Groups 1 and 2, all patients received a daily low-dose program (1–1.5 mg/kg each day) with target dosage of six mg/kg. Induction therapy was combined with standard immunosuppressive regimen consisting of calcineurin inhibitors, mycophenolate/the mammalian target of rapamycin inhibitors and corticosteroids. Results There was no significant difference in patient characteristics among groups. The outcomes of infection rate, biopsy-proven acute rejection, post-transplant diabetes mellitus, graft survival, and patient survival were similar among groups. Compared to the daily low-dose ATG regimen, the intraoperative modest-dose regimen did not cause more dose interruption and hence was more likely to reach the target ATG dosage. The intraoperative modest-dose regimen also seemed to reduce the rate of DGF. Discussion In recent years, a trend of using a “lower” dose of ATG has seemed to emerge. Our results suggest intraoperative modest-dose ATG followed by daily low-dose ATG regimen was safe and effective in cadaveric renal transplantations for preventing DGF, AR, and graft loss.

scholarly journals Living unrelated donor kidney transplantation: A fourteen-year experience

2010 ◽  
Vol 67 (12) ◽  
pp. 998-1002 ◽  
Author(s):  
Ljiljana Ignjatovic ◽  
Dragan Jovanovic ◽  
Goran Kronja ◽  
Aleksandar Dujic ◽  
Mihailo Maric ◽  
...  
Keyword(s):  
Graft Function ◽  
Control Group ◽  
Unrelated Donor ◽  
Organ Shortage ◽  
Hla Matching ◽  
Group I ◽  
Kidney Transplantations ◽  
Stage Renal Disease ◽  
End Stage

Background. In countries without a national organization for retrieval and distribution of organs of the deceased donors, problem of organ shortage is still not resolved. In order to increase the number of kidney transplantations we started with the program of living unrelated - spousal donors. The aim of this study was to compare treatment outcome and renal graft function in patients receiving the graft from spousal and those receiving ghe graft from living related donors. Method. We retrospectively identified 14 patients who received renal allograft from spousal donors between 1996 and 2009 (group I). The control group consisted of 14 patients who got graft from related donor retrieved from the database and matched than with respect to sex, age, kidney disease, immunological and viral pretransplant status, the initial method of the end stage renal disease treatment and ABO compatibility. In the follow-up period of 41 ? 38 months we recorded immunosuppressive therapy, surgical complications, episodes of acute rejection, CMV infection and graft function, assessed by serum creatinine levels at the beginning and in the end of the follow-up period. All patients had pretransplant negative cross-match. In ABO incompatible patients pretransplant isoagglutinine titer was zero. Results. The patients with a spousal donor had worse HLA matching. There were no significant differences between the groups in surgical, infective, immunological complications and graft function. Two patients from the group I returned to hemodialysis after 82 and 22 months due to serious comorbidities. Conclusion. In spite of the worse HLA matching, graft survival and function of renal grafts from spousal donors were as good as those retrieved from related donors.

P1720POSTTRANSPLANT TUBERCULOSIS IN LIVE DONOR RENAL TRANSPLANTATION : A SINGLE-CENTER EXPERIENCE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ahmed Mohamed Naguib Attiya ◽  
Mohamed Hamed abbas ◽  
Ahmed Mansour Hassan Abdel-Rahman ◽  
Ayman Refaie
Keyword(s):  
Kidney Function ◽  
Induction Therapy ◽  
De Novo ◽  
Immunosuppressive Agents ◽  
Renal Transplant Recipients ◽  
Live Donor ◽  
Single Center ◽  
Significant Difference ◽  
The Impact ◽  
Pulse Steroid

Abstract Background and Aims Tuberculosis (TB) is one of the not uncommon serious bacterial infections which affect renal transplant recipients notably in endemic areas. Posttransplant TB occurs peculiarly due to reactivation of latent infection in the recipient or acquiring de novo infection after transplantation or rarely as donor transmitted infection. The aim of this study is to investigate the impact of TB disease and treatment drugs on renal graft and assess the risk factors for graft dysfunction during and after course of treatment. Method This retrospective single-center study investigated 3000 patients who underwent live donor renal allograft transplantation in our center between the years 1988-2019. TB diagnosis was confirmed in 44 patients. All proven-TB patients were evaluated regarding pretransplant demographic and immunological data. Posttransplant evaluation included kidney function tests, immunosuppressive therapy regimens, incidence of rejection episodes and anti-rejection therapies before, during and after TB. Results Patients were predominantly young (32±9.8 years), male (60%), There was no significant difference regarding other pretransplant demographic and immunological data. Regarding induction therapy, 13 patients received induction therapy; 7 patients received ATG, 6 patients received basiliximab and 31 patients did not receive induction therapy with no significant difference (p=0.07). Concerning maintenance immunosuppressive agents, no significant difference was found regarding different protocols of immunosuppression (p=0.11); however, regarding total dose of the steroid in 1st three months post-transplant, there was significant difference (p=0.017). As regards to rejection episodes, 16 patients were not exposed to rejection episodes before TB, 27 patients developed cellular rejection and only 1 patient developed humoral rejection with no statistical difference (p=0.18). In reference to management of rejection episodes, 25 patients received pulse steroid, 2 patients received pulse steroid and ATG, 1 patient received pulse steroid and plasma exchange (p=0.28) prior to infection with TB with no significant difference. A significant increase was noticed in serum Cr during TB disease and treatment:1.5 mg/dL at baseline (Crbase), 1.8 mg/dL at diagnosis (P=0.43 vs. Crbase), and 2.0 mg/dL during the peak (P=0.03 vs. Crbase). Conclusion Posttransplant TB drastically affects kidney function and graft outcome. Cumulative steroid dose in the first 3 months may be considered a risk factor for TB.

IL-10-592 A/C Gene Polymorphism and Cytokine Levels are Associated with Susceptibility to Drug Resistance in Tuberculosis

2020 ◽  
Vol 8 (3) ◽  
pp. 103-112
Author(s):  
Atefeh SADEGHI SHERMEH ◽  
Majid KHOSHMIRSAFA ◽  
Ali-Akbar DELBANDI ◽  
Payam TABARSI ◽  
Esmaeil MORTAZ ◽  
...  
Keyword(s):  
Serum Levels ◽  
World Health ◽  
Control Group ◽  
Drug Resistant ◽  
Nucleotide Polymorphisms ◽  
Genotype Frequencies ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Health Organization ◽  
And Function

Introduction: Tuberculosis (TB) and especially resistant forms of it have a substantial economic burden on the community health system for diagnosis and treatment each year. Thus, investigation of this field is a priority for the world health organization (WHO). Cytokines play important roles in the relationship between the immune system and tuberculosis. Genetic variations especially single nucleotide polymorphisms (SNPs) impact cytokine levels and function against TB. Material and Methods: In this research SNPs in IFN-γ (+874 T/A) and IL-10 (-592 A/C) genes, and the effects of these SNPs on cytokine levels in a total of 87 tuberculosis patients and 100 healthy controls (HCs) were studied. TB patients divided into two groups: 1) 67 drug-sensitive (DS-TB) and 2) 20 drug-resistant (DR-TB) according to drug sensitivity test using polymerase chain reaction (PCR). For the genotyping of two SNPs, the PCR-based method was used and IFN-γ and IL-10 levels were measured by ELISA in pulmonary tuberculosis (PTB) and control group. Results: In -592A/C SNP, only two genotypes (AA, AC) were observed and both genotypes showed statistically significant differences between DR-TB and HCs (p=0.011). IL-10 serum levels in PTB patients were higher than HCs (p=0.02). The serum levels of IFN-γ were significantly higher in DS-TB patients than that of the other two groups (p<0.001); however, no significant differences were observed for allele and genotype frequencies in IFN-γ +874. Conclusions: Our results suggest that the SNP at -592 position of IL-10 gene may be associated with the susceptibility to DR-TB. However, further investigation is necessary. Keywords: Polymorphism, IFN-γ, IL-10, tuberculosis, drug-resistant tuberculosis

scholarly journals Epidemiology, Risk Factors, and Outcomes of Opportunistic Infections after Kidney Allograft Transplantation in the Era of Modern Immunosuppression: A Monocentric Cohort Study

2019 ◽  
Vol 8 (5) ◽  
pp. 594 ◽  
Author(s):  
Philippe Attias ◽  
Giovanna Melica ◽  
David Boutboul ◽  
Nathalie De Castro ◽  
Vincent Audard ◽  
...  
Keyword(s):  
Risk Factors ◽  
Protective Factor ◽  
Opportunistic Infections ◽  
Control Group ◽  
Kidney Allograft ◽  
Extended Criteria Donor ◽  
Allograft Transplantation ◽  
Kidney Recipients ◽  
Independent Risk Factors ◽  
Kidney Transplantations

Epidemiology of opportunistic infections (OI) after kidney allograft transplantation in the modern era of immunosuppression and the use of OI prevention strategies are poorly described. We retrospectively analyzed a single-center cohort on kidney allograft adult recipients transplanted between January 2008 and December 2013. The control group included all kidney recipients transplanted in the same period, but with no OI. We analyzed 538 kidney transplantations (538 patients). The proportion of OI was 15% (80 and 72 patients). OI occurred 12.8 (6.0–31.2) months after transplantation. Viruses were the leading cause (n = 54, (10%)), followed by fungal (n = 15 (3%)), parasitic (n = 6 (1%)), and bacterial (n = 5 (0.9%)) infections. Independent risk factors for OI were extended criteria donor (2.53 (1.48–4.31), p = 0.0007) and BK viremia (6.38 (3.62–11.23), p < 0.0001). High blood lymphocyte count at the time of transplantation was an independent protective factor (0.60 (0.38–0.94), p = 0.026). OI was an independent risk factor for allograft loss (2.53 (1.29–4.95), p = 0.007) but not for patient survival. Post-kidney transplantation OIs were mostly viral and occurred beyond one year after transplantation. Pre-transplantation lymphopenia and extended criteria donor are independent risk factors for OI, unlike induction therapy, hence the need to adjust immunosuppressive regimens to such transplant candidates.

Comparative effects of Orchis anatolica vs. the red Korean Panax ginseng treatments on testicular structure and function of adult male mice

2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Nabil A. Khouri ◽  
Haytham M. Daradka ◽  
Mohammed Z. Allouh ◽  
Ahmad S. Alkofahi
Keyword(s):  
Panax Ginseng ◽  
Male Fertility ◽  
Virgin Female ◽  
Reproductive Organs ◽  
Serum Markers ◽  
Structure And Function ◽  
Control Group ◽  
Male Mice ◽  
Fertility Potential ◽  
And Function

Abstract: The effects of: Both plants were administered orally to two separate mice groups at a dose of 800 mg/kg/day for 35 days and compared with control group. After treatment, 5 mice of each group were sacrificed and total mice weights, reproductive organs’ weights, spermatogenesis, and androgenic serum markers were investigated. The remaining mice from all groups were allowed to mate with virgin female mice to explore male fertility potential.: Results indicated that body and organs’ weights were increased significantly in mice treated with: We can conclude that

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