-
Experimental and Clinical... Apr 2024Induction treatment in renal transplant is associated with better graft survival. However, intensified immunosuppression is known to cause unwanted side effects such as... (Comparative Study)
Comparative Study
OBJECTIVES
Induction treatment in renal transplant is associated with better graft survival. However, intensified immunosuppression is known to cause unwanted side effects such as infection and malignancy. Furthermore, the effects of the routine use of immunosuppressants in low-risk kidney transplant recipients are still not clear. In this study, we assessed the first-year safety and efficacy of induction treatment.
MATERIALS AND METHODS
We examined first living donor kidney transplant patients who were on tacrolimus based immunosuppression therapy. We formed 3 groups according to the induction status: antithymocyte globulin induction, basiliximab induction, and no induction. We collected outcome data on delayed graft function, graft loss, creatinine levels, estimated glomerular filtration rates, acute rejection episodes, hospitalization episodes, and infection episodes, including cytomegalovirus infection and bacterial infections.
RESULTS
We examined a total of 126 patients (age 35 ± 12 years; 65% male). Of them, 25 received antithymocyte globulin, 52 received basiliximab, and 49 did notreceive any induction treatment. We did not observe any statistically significant difference among the 3 groups in terms of acute rejection episodes, delayed graft function, and first-year graft loss. The estimated glomerular filtration rates were similar among the groups. Overall bacterial infectious complications and cytomegalovirus infection showed similar prevalence among all groups. Hospitalization was less common in the induction-free group.
CONCLUSIONS
In low-risk patients, induction-free regimens could be associated with a better safety profile without compromising graft survival. Therefore, induction treatment may be disregarded in first living donor transplant patients who receive tacrolimusbased triple immunosuppression treatment.
Topics: Humans; Kidney Transplantation; Basiliximab; Immunosuppressive Agents; Female; Male; Tacrolimus; Living Donors; Adult; Antilymphocyte Serum; Middle Aged; Treatment Outcome; Time Factors; Graft Rejection; Graft Survival; Risk Factors; Retrospective Studies; Delayed Graft Function; Young Adult; Recombinant Fusion Proteins; Calcineurin Inhibitors; Drug Therapy, Combination
PubMed: 38742317
DOI: 10.6002/ect.2023.0010 -
Transplantation Proceedings May 2024There is continuous growth of combined liver-kidney transplantation (CLKTx) numbers with remarkable outcomes, especially among patient with liver cirrhosis and end-stage...
BACKGROUND
There is continuous growth of combined liver-kidney transplantation (CLKTx) numbers with remarkable outcomes, especially among patient with liver cirrhosis and end-stage renal disease. The aim was to present a single center experience.
METHODS
Twenty patients (9 males) with a mean age of 48 (range: 20-62) years underwent CLKTx from 2005 to 2022. Indications were polycystic liver and kidney diseases (ADPKD) in 12 cases, cirrhosis due to hepatitis (4 patients), and 1 case of amyloidosis, alcoholic liver disease, nonalcoholic steatosis, and congenital hepatic fibrosis with concomitant glomerulonephritis. After hepatectomy, half of the patients had orthotopic liver transplantation with piggy-back technique, and the other had conventional technique. All but 1 recipient had biliary end-to-end anastomosis. 3 patients had preemptive kidney graft transplantation. 4 underwent simultaneous right-side nephrectomy due to volume of the right kidney. Kidney was transplanted from the separate incision after abdominal closure with typical anastomoses. Tacrolimus, mycophenolate mofetile, basiliximab, and steroids were applied for all recipients.
RESULTS
Mean follow-up was 57.7 ± 54 months. No primary non-function of the grafts occurred. Delayed kidney graft function (DGF) occurred in 8 patients. Three-month, 1-year, and 5-year cumulative survival rates were: 90%, 80%, and 72% respectively. None of the patients required retransplantation, and 1 recipient returned to hemodialysis 19 months after transplantation. Preemptive kidney transplantation and simultaneous right-side nephrectomy were not significant for DGF and recipient survival. No deaths within the first year occurred in piggy-back technique.
CONCLUSIONS
CLKTx is safe and effective in the treatment of both liver and kidney failure.
PubMed: 38719623
DOI: 10.1016/j.transproceed.2024.03.014 -
Journal of Clinical Medicine Apr 2024Potent immunosuppression lowers the incidence of acute graft rejection but increases the risk of infections. In order to decrease either infectious complications or...
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. 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. : 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. : 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.
PubMed: 38673435
DOI: 10.3390/jcm13082162 -
Indian Journal of Nephrology 2024In view of ever-increasing end-stage renal disease (ESRD) population but inadequate availability of suitable donors, ABO-incompatible (ABOi) transplantation can be an...
INTRODUCTION
In view of ever-increasing end-stage renal disease (ESRD) population but inadequate availability of suitable donors, ABO-incompatible (ABOi) transplantation can be an important void filler. However, at present, ABOi transplantation is limited to a few centers in India and there is a lack of adequate experience and expertise to guide this program to other centers in the country.
METHODS
Data of all the ABOi transplants performed from 2012 to 2021 in a tertiary care hospital was retrospectively analyzed. The anti-ABO antibody (IgG) titers (≤1:4) were considered safe before transplantation. Desensitization included rituximab, plasma exchange, or selective immunoadsorption column. Tacrolimus and mycophenolate mofetil were initiated at day -7. Induction agents included ATG, ATLG, basiliximab, or no induction. Postoperatively, anti-ABO titers were done daily for 2 weeks.
RESULTS
A total of 202 patients underwent transplantation; of these, 195 patients whose data were for available for 12 months were included in the study. Mean duration of follow-up was 28.9 ± 21.7 months. UTI was the most common source of infection, occurring in almost half (46.1%) of the patients. Antibody-mediated rejection (ABMR; 15%) was common in the first year. Patient survival was 86.6% (169/195) at 1 year. Sepsis was the most common of death in more than two-thirds of the population, including coronavirus disease 2019 (COVID-19)-associated mortality in nine patients (4.6%). Death-censored graft survival was 89.3% (174/195). AMR was the leading cause of graft loss in almost half of the patients.
CONCLUSION
ABOi should be considered in ESRD patients for whom suitable ABO-compatible donor is not available. Higher rate of rejection and infection are still a major concern.
PubMed: 38645921
DOI: 10.4103/ijn.ijn_247_22 -
Frontiers in Immunology 2024Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced... (Review)
Review
Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of infection. Thus, applying IL inhibitors might impact an individual's susceptibility to infections. Variations in the severity of infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings.
Topics: Humans; Interleukin-17; Interleukin Inhibitors; Prospective Studies; Candidiasis; Interleukin-23
PubMed: 38605952
DOI: 10.3389/fimmu.2024.1372693 -
Frontiers in Oncology 2024Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation...
Decreasing the steroid rapidly may help to improve the clinical outcomes of patients with intestinal steroid-refractory acute graft-versus-host disease receiving basiliximab treatment.
Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%-26.1%), 22.8% (95% CI 14.2%-31.4%) and 32.8% (95% CI 24.1%-41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%-84.9%), 72.7% (95% CI 63.7%-81.7%), and 62.3% (95% CI 53.5%-71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.
PubMed: 38595816
DOI: 10.3389/fonc.2024.1390438 -
Human Immunology Mar 2024Intestinal transplantation poses a unique challenge in the field of solid organ transplantation. The combination of tacrolimus and prednisone stands as the foundational...
INTRODUCTION
Intestinal transplantation poses a unique challenge in the field of solid organ transplantation. The combination of tacrolimus and prednisone stands as the foundational cornerstone of maintenance immunosuppression in the field of intestinal transplantation. This case series aims to describe 1-year clinical outcomes of 5 intestinal transplant recipients who received a novel immunosuppression regimen consisting of monthly basiliximab, sublingual tacrolimus, and prednisone.
METHODS
A retrospective analysis of patients who underwent intestinal transplantation in our center between January 01, 2020, and January 31, 2022, was conducted. Each recipient was followed for at least 1-year post-transplant. Recipient baseline demographics, clinical characteristics, and follow-up data were obtained from the electronic health records. Data collection included recipient demographics (age, sex, race/ethnicity, BMI), cause of intestinal failure, immunological data, infectiology data and treatment information.
RESULTS
A total of five patients underwent intestinal transplantation, of which two males (40 %) and three females (60 %), with a median age of 20.1 years (17.4-28.8). The median (IQR) tacrolimus trough by month 1 was 10.4 (8.4-13.2) ng/mL. Subsequently, the median (IQR) tacrolimus troughs at specified periods are as follows, respectively: month 3: 10.2 (8.2-13.2) ng/mL; month 6: 8.4 (7.6-9.6) ng/mL; and month 12: 8.8 (6.2-9.8) ng/mL. Three patients (60.0 %) had biopsy proven rejection, but all of them had resolution after the optimization of immunosuppression. All patients were alive and had a functioning intestinal allograft at 1-year.
CONCLUSION
The combination of monthly basiliximab, sublingual tacrolimus, and prednisone is an effective novel maintenance immunosuppression in intestinal transplantation. A larger and more extended study duration would be necessary to thoroughly assess the safety and sustained benefits of the novel maintenance immunosuppression regimen.
PubMed: 38480040
DOI: 10.1016/j.humimm.2024.110787 -
Progress in Transplantation (Aliso... Jun 2024Delayed graft function in kidney transplant is associated with an increased risk of rejection and graft loss. Use of rabbit antithymocyte globulin induction in delayed...
Delayed graft function in kidney transplant is associated with an increased risk of rejection and graft loss. Use of rabbit antithymocyte globulin induction in delayed graft function has been correlated with less rejection compared to basiliximab, but optimal dosing remains unknown. The purpose of this evaluation was to retrospectively assess the short-term effectiveness and tolerability of a clinical protocol that increased the net state of immunosuppression in delayed graft function kidney transplant recipients using cumulative 6 mg/kg rabbit antithymocyte globulin induction. This retrospective cohort included 88 kidney transplant recipients with delayed graft function, transplanted between January 2017 and March 2021, who either received cumulative 4.5 mg/kg pre-protocol or 6 mg/kg post-protocol rabbit antithymocyte globulin. Outcomes evaluated were biopsy-proven acute rejection and incidence of graft loss, infection, and cytopenia at 6 months. A significant reduction of biopsy-proven acute rejection incidence occurred post-protocol implementation (10/33, 30.3% vs 6/55, 10.9%; = .04). Of those with rejection, significantly less post-protocol patients were classified as acute cellular rejection (9/10, 90.0% vs 2/6, 33.3%; = .04). No death-censored graft loss was observed in either group. Rates of cytopenia and infection were similar pre- versus post-protocol implementation. Increasing the exposure to rabbit antithymocyte globulin and maintenance immunosuppression in delayed graft function kidney transplant recipients was tolerable and significantly reduced rejection occurrence at 6 months.
Topics: Humans; Kidney Transplantation; Antilymphocyte Serum; Retrospective Studies; Male; Female; Middle Aged; Graft Rejection; Delayed Graft Function; Immunosuppressive Agents; Adult; Rabbits; Graft Survival; Animals; Treatment Outcome; Aged
PubMed: 38465633
DOI: 10.1177/15269248241237816 -
BMC Medicine Feb 2024For patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD), effective second-line regimens are urgently needed. Mesenchymal stromal cells (MSCs)... (Randomized Controlled Trial)
Randomized Controlled Trial
Mesenchymal stromal cells plus basiliximab improve the response of steroid-refractory acute graft-versus-host disease as a second-line therapy: a multicentre, randomized, controlled trial.
BACKGROUND
For patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD), effective second-line regimens are urgently needed. Mesenchymal stromal cells (MSCs) have been used as salvage regimens for SR-aGVHD in the past. However, clinical trials and an overall understanding of the molecular mechanisms of MSCs combined with basiliximab for SR-aGVHD are limited, especially in haploidentical haemopoietic stem cell transplantation (HID HSCT).
METHODS
The primary endpoint of this multicentre, randomized, controlled trial was the 4-week complete response (CR) rate of SR-aGVHD. A total of 130 patients with SR-aGVHD were assigned in a 1:1 randomization schedule to the MSC group (receiving basiliximab plus MSCs) or control group (receiving basiliximab alone) (NCT04738981).
RESULTS
Most enrolled patients (96.2%) received HID HSCT. The 4-week CR rate of SR-aGVHD in the MSC group was obviously better than that in the control group (83.1% vs. 55.4%, P = 0.001). However, for the overall response rates at week 4, the two groups were comparable. More patients in the control group used ≥ 6 doses of basiliximab (4.6% vs. 20%, P = 0.008). We collected blood samples from 19 consecutive patients and evaluated MSC-derived immunosuppressive cytokines, including HO1, GAL1, GAL9, TNFIA6, PGE2, PDL1, TGF-β and HGF. Compared to the levels before MSC infusion, the HO1 (P = 0.0072) and TGF-β (P = 0.0243) levels increased significantly 1 day after MSC infusion. At 7 days after MSC infusion, the levels of HO1, GAL1, TNFIA6 and TGF-β tended to increase; however, the differences were not statistically significant. Although the 52-week cumulative incidence of cGVHD in the MSC group was comparable to that in the control group, fewer patients in the MSC group developed cGVHD involving ≥3 organs (14.3% vs. 43.6%, P = 0.006). MSCs were well tolerated, no infusion-related adverse events (AEs) occurred and other AEs were also comparable between the two groups. However, patients with malignant haematological diseases in the MSC group had a higher 52-week disease-free survival rate than those in the control group (84.8% vs. 65.9%, P = 0.031).
CONCLUSIONS
For SR-aGVHD after allo-HSCT, especially HID HSCT, the combination of MSCs and basiliximab as the second-line therapy led to significantly better 4-week CR rates than basiliximab alone. The addition of MSCs not only did not increase toxicity but also provided a survival benefit.
Topics: Humans; Basiliximab; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Steroids; Mesenchymal Stem Cells; Transforming Growth Factor beta; Acute Disease; Mesenchymal Stem Cell Transplantation
PubMed: 38413930
DOI: 10.1186/s12916-024-03275-5 -
Microorganisms Jan 2024The importance of lung microbiome changes in developing chronic lung allograft dysfunction (CLAD) after lung transplantation is poorly understood. The lung...
The importance of lung microbiome changes in developing chronic lung allograft dysfunction (CLAD) after lung transplantation is poorly understood. The lung microbiome-immune interaction may be critical in developing CLAD. In this context, examining alterations in the microbiome and immune cells of the lungs following CLAD, in comparison to the lung condition immediately after transplantation, can offer valuable insights. Four adult patients who underwent lung retransplantation between January 2019 and June 2020 were included in this study. Lung tissues were collected from the same four individuals at two different time points: at the time of the first transplant and at the time of the explantation of CLAD lungs at retransplantation due to CLAD. We analyzed whole-genome sequencing using the Kraken2 algorithm and quantified the cell fractionation from the bulk tissue gene expression profile for each lung tissue. Finally, we compared the differences in lung microbiome and immune cells between the lung tissues of these two time points. The median age of the recipients was 57 years, and most (75%) had undergone lung transplants for idiopathic pulmonary fibrosis. All patients were administered basiliximab for induction therapy and were maintained on three immunosuppressants. The median CLAD-free survival term was 693.5 days, and the median time to redo the lung transplant was 843.5 days. Bacterial diversity was significantly lower in the CLAD lungs than at transplantation. Bacterial diversity tended to decrease according to the severity of the CLAD. , , , , and genera were uniquely identified in CLAD, whereas no taxa were identified in lungs at transplantation. In particular, six taxa, including , , , , , and were uniquely detected in CLAD. Among immune cells, CD8+ T cells were significantly increased, while neutrophils were decreased in the CLAD lung. In conclusion, unique changes in lung microbiome and immune cell composition were confirmed in lung tissue after CLAD compared to at transplantation.
PubMed: 38399691
DOI: 10.3390/microorganisms12020287