-
The Cochrane Database of Systematic... Nov 2014Most people who receive a kidney transplant die from either cardiovascular disease or cancer before their transplant fails. The most common reason for someone with a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Most people who receive a kidney transplant die from either cardiovascular disease or cancer before their transplant fails. The most common reason for someone with a kidney transplant to lose the function of their transplanted kidney necessitating return to dialysis is chronic kidney transplant scarring. Immunosuppressant drugs have side effects that increase risks of cardiovascular disease, cancer and chronic kidney transplant scarring. Belatacept may provide sufficient immunosuppression while avoiding unwanted side effects of other immunosuppressant drugs. However, high rates of post-transplant lymphoproliferative disease (PTLD) have been reported when belatacept is used in particular kidney transplant recipients at high dosage.
OBJECTIVES
1) Compare the relative efficacy of belatacept versus any other primary immunosuppression regimen for preventing acute rejection, maintaining kidney transplant function, and preventing death. 2) Compare the incidence of several adverse events: PTLD; other malignancies; chronic transplant kidney scarring (IF/TA); infections; change in blood pressure, lipid and blood sugar control. 3) Assess any variation in effects by study, intervention and recipient characteristics, including: differences in pre-transplant Epstein Barr virus serostatus; belatacept dosage; and donor-category (living, standard criteria deceased, or extended criteria deceased).
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register to 1 September 2014 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
Randomised controlled trials (RCT) that compared belatacept versus any other immunosuppression regimen in kidney transplant recipients were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data for study quality and transplant outcomes and synthesized results using random effects meta-analysis, expressed as risk ratios (RR) and mean differences (MD), both with 95% confidence intervals (CI). Subgroup analyses and univariate meta-regression were used to investigate potential heterogeneity.
MAIN RESULTS
We included five studies that compared belatacept and calcineurin inhibitors (CNI) that reported data from a total of 1535 kidney transplant recipients. Of the five studies, three (478 participants) compared belatacept and cyclosporin and two (43 recipients) compared belatacept and tacrolimus. Co-interventions included basiliximab (4 studies, 1434 recipients); anti-thymocyte globulin (1 study, 89 recipients); alemtuzumab (1 study, 12 recipients); mycophenolate mofetil (MMF, 5 studies, 1509 recipients); sirolimus (1 study, 26 recipients) and prednisone (5 studies, 1535 recipients).Up to three years following transplant, belatacept and CNI-treated recipients were at similar risk of dying (4 studies, 1516 recipients: RR 0.75, 95% CI 0.39 to 1.44), losing their kidney transplant and returning to dialysis (4 studies, 1516 recipients: RR 0.91, 95% CI 0.61 to 1.38), and having an episode of acute rejection (4 studies, 1516 recipients: RR 1.56, 95% CI 0.85 to 2.86). Belatacept-treated kidney transplant recipients were 28% less likely to have chronic kidney scarring (3 studies, 1360 recipients: RR 0.72, 95% CI 0.55 to 0.94) and also had better graft function (measured glomerular filtration rate (GFR) (3 studies 1083 recipients): 10.89 mL/min/1.73 m², 95% CI 4.01 to 17.77; estimated GFR (4 studies, 1083 recipients): MD 9.96 mL/min/1.73 m², 95% CI 3.28 to 16.64) than CNI-treated recipients. Blood pressure was lower (systolic (2 studies, 658 recipients): MD -7.51 mm Hg, 95% CI -10.57 to -4.46; diastolic (2 studies, 658 recipients): MD -3.07 mm Hg, 95% CI -4.83 to -1.31, lipid profile was better (non-HDL (3 studies 1101 recipients): MD -12.25 mg/dL, 95% CI -17.93 to -6.57; triglycerides (3 studies 1101 recipients): MD -24.09 mg/dL, 95% CI -44.55 to -3.64), and incidence of new-onset diabetes after transplant was reduced by 39% (4 studies (1049 recipients): RR 0.61, 95% CI 0.40 to 0.93) among belatacept-treated versus CNI-treated recipients.Risk of PTLD was similar in belatacept and CNI-treated recipients (4 studies, 1516 recipients: RR 2.79, 95% CI 0.61 to 12.66) and was no different among recipients who received different belatacept dosages (high versus low dosage: ratio of risk ratios (RRR) 1.06, 95% CI 0.11 to 9.80, test of difference = 0.96) or among those who were Epstein Barr virus seronegative compared with those who were seropositive before their kidney transplant (seronegative versus seropositive; RRR 1.49, 95% CI 0.15 to 14.76, test for difference = 0.73).The belatacept dose used (high versus low), type of donor kidney the recipient received (extended versus standard criteria) and whether the kidney transplant recipient received tacrolimus or cyclosporin made no difference to kidney transplant survival, incidence of acute rejection or estimated GFR. Selective outcome reporting meant that data for some key subgroup comparisons were sparse and that estimates of the effect of treatment in these groups of recipients remain imprecise.
AUTHORS' CONCLUSIONS
There is no evidence of any difference in the effectiveness of belatacept and CNI in preventing acute rejection, graft loss and death, but treatment with belatacept is associated with less chronic kidney scarring and better kidney transplant function. Treatment with belatacept is also associated with better blood pressure and lipid profile and a lower incidence of diabetes versus treatment with a CNI. Important side effects (particularly PTLD) remain poorly reported and so the relative benefits and harms of using belatacept remain unclear. Whether short-term advantages of treatment with belatacept are maintained over the medium- to long-term or translate into better cardiovascular outcomes or longer kidney transplant survival with function remains unclear. Longer-term, fully reported and published studies comparing belatacept versus tacrolimus are needed to help clinicians decide which patients might benefit most from using belatacept.
Topics: Abatacept; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Basiliximab; Calcineurin Inhibitors; Cyclosporine; Graft Rejection; Graft Survival; Humans; Immunoconjugates; Immunosuppressive Agents; Kidney Transplantation; Lymphoproliferative Disorders; Mycophenolic Acid; Prednisone; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Sirolimus; Tacrolimus
PubMed: 25416857
DOI: 10.1002/14651858.CD010699.pub2 -
Transplant International : Official... Jul 2013Induction therapy, the initial high-dose bolus of immunosuppression given perioperatively to transplant patients, is almost ubiquitous in pancreas transplantation.... (Review)
Review
Induction therapy, the initial high-dose bolus of immunosuppression given perioperatively to transplant patients, is almost ubiquitous in pancreas transplantation. Despite the frequent use, scientific data on the risks and benefits of induction therapy are scarce, especially as it concerns use specifically for pancreas transplantation. Indeed, none of the currently used induction agents are approved as induction therapy for pancreas transplantation, yet potential benefit is largely extrapolated from trials in kidney transplant recipients. This review summarizes which induction therapy agents are available both now and historically, their mechanisms of action, and provides an overview of the published literature describing the use of these agents in simultaneous pancreas-kidney transplant and solitary pancreas transplant recipients. In summary, there are two multicenter randomized trials, several single-center randomized trials, and many other single-center descriptive reports. Overall, the main benefit of induction therapy is the ability to wean steroids earlier, and the main downside is a higher risk of opportunistic infections. Despite a lack of solid evidence, over 90% of pancreas transplants performed annually in the United States receive some type of induction immunosuppression.
Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Basiliximab; Humans; Immunosuppressive Agents; Kidney Transplantation; Muromonab-CD3; Pancreas Transplantation; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins
PubMed: 23672537
DOI: 10.1111/tri.12122 -
Transplantation Direct Aug 2021The unplanned use of dual induction therapy with interleukin-2 receptor-blocking antibodies (IL2rAb) and antithymocyte globulin (ATG) may portend adverse outcomes.
UNLABELLED
The unplanned use of dual induction therapy with interleukin-2 receptor-blocking antibodies (IL2rAb) and antithymocyte globulin (ATG) may portend adverse outcomes.
METHODS
We used national transplant registry data to study clinical correlates and outcomes of single versus dual induction therapy in adult kidney-only transplant recipients in the United States (2005-2018). The risk of death and graft loss at 1 and 5 y, according to induction therapy type, was assessed using multivariate Cox regression analysis (adjusted hazard ratio with 95% upper and lower confidence limits [aHR]).
RESULTS
Of the 157 351 recipients included in the study, 67% were treated with ATG alone, 29% were treated with IL2rAb alone, and 5% were treated with both. Compared with IL2rAb alone, the strongest correlates of dual induction included Black race, calculated panel reactive antibody ≥80%, prednisone-sparing maintenance immunosuppression, more recent transplant eras, longer cold ischemia time, and delayed graft function. Compared with ATG alone, dual induction was associated with an increased 5-y risk of death (aHR 1.15; < 0.0001), death-censored graft failure (aHR 1.13; < 0.05), and all-cause graft failure (aHR 1.12; < 0.0001).
CONCLUSIONS
Further research is needed to develop risk-prediction tools to further inform optimal, individualized induction protocols for kidney transplant recipients.
PubMed: 35836670
DOI: 10.1097/TXD.0000000000001190 -
American Journal of Hematology Aug 2020Acute graft-vs-host disease (aGVHD) is one of the most important causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT),...
Acute graft-vs-host disease (aGVHD) is one of the most important causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly for those with steroid-refractory (SR)-aGVHD. We aimed to identify the prognostic factors and long-term clinical outcomes of basiliximab treatment for SR-aGVHD. Basiliximab was administered on days 1, 3, and 8, and repeated weekly until aGVHD was less than grade II, or patients showed no response after four doses. Out of 1498 patients receiving allo-HSCT, 230 patients with SR-aGVHD were enrolled. Grade III to IV aGVHD before basiliximab treatment significantly and independently predicted a poorer response to basiliximab in multivariate analysis. And, the cumulative incidence of overall response at 14 days, 28 days, and 56 days after treatment was 41.4% vs 23.1% (P = .023), 70.2% vs 43.6% (P = .002), and 80.1% vs 66.7% (P = .013), respectively. This was for those with grade II and grade III to IV aGVHD. Patients receiving more than four doses of basiliximab had higher rates of infections. The 4-year cumulative incidence of total and severe chronic GVHD after basiliximab treatment was 44.8% (95% CI 38.3%-51.3%) and 2.2% (95% CI 0.3%-4.1%), respectively. The 4-year cumulative incidence of relapse, non-relapse mortality, disease-free survival, and overall survival after basiliximab treatment was 11.3% (95% CI 7.2%-15.4%), 30.0% (95% CI 24.1%-35.9%), 58.7% (95% CI 52.3%-65.1%), and 61.7% (95% CI 55.4%-68.0%), respectively. Comorbidities before allo-HSCT and refined Minnesota aGVHD risk score at diagnosis had significant influences on long-term survival. Thus, basiliximab was a safe and effective treatment for patients with SR-aGVHD.
Topics: Acute Disease; Adult; Basiliximab; Female; Follow-Up Studies; Graft vs Host Disease; Humans; Immunosuppressive Agents; Male; Prognosis; Retrospective Studies; Survival Analysis; Treatment Outcome; Young Adult
PubMed: 32311156
DOI: 10.1002/ajh.25839 -
Experimental and Clinical... Feb 2017We review different immunosuppressant protocols used for living-donor kidney transplant recipients at our center.
OBJECTIVES
We review different immunosuppressant protocols used for living-donor kidney transplant recipients at our center.
MATERIALS AND METHODS
Many prospective randomized studies from our center have been reported between March 1976 and 2016, with more than 2700 renal transplant procedures conducted. The first study was a prospective randomized trial of azathioprine versus cyclosporine. The second study compared triple therapy (prednisolone + azathioprine + cyclosporine) versus conventional therapy (prednisolone + azathioprine). The third study was a cost-saving study, in which 100 patients received ketoconazole along with the triple regimen. Another trial demonstrated the advantages of a microemulsion form of cyclosporine. A subsequent trial compared calcineurin inhibitor minimization versus avoidance protocols. Rescue therapies were carried out to intensify immunosuppressive regimens after repeated rejection. In addition, steroid-free regimens were evaluated during both short- and long-term treatment. A recent trial reported a step-forward avoidance protocol with a calcineurin inhibitor and a steroid-free regimen, whereas another current study is the TRANSFORM one. The rationale behind antibody therapy was tho roughly evaluated among living-donor renal trans plant recipients with different agents, including basiliximab, daclizumab, antithymocyte globulin, and alemtuzumab.
RESULTS
Earlier studies have demonstrated the efficacy of conventional regimens without induction therapy, especially in longer follow-up. The standard triple therapy has emerged with intensified immunosuppressive and lowered dose of each drug, especially cyclosporine. In minimization studies, no significant differences were encountered regarding patient and graft survival, even in the long-term. Steroid avoidance was safe and effective. Calcineurin inhibitors and steroid-free regimens have shown comparable patient and graft survival. Induction therapy has lowered the incidence and severity of acute rejection.
CONCLUSIONS
A better 5-year graft survival and less posttransplant complications have been achieved with steroid avoidance after induction with basiliximab. Induction therapy did not affect graft and patient survival rates despite lowered incidence and severity of acute rejections.
Topics: Drug Administration Schedule; Drug Substitution; Drug Therapy, Combination; Egypt; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome
PubMed: 28260425
DOI: 10.6002/ect.mesot2016.L46 -
Transplantation Direct Dec 2022The success of orthotopic liver transplantation as a life-saving treatment has led to new indications and a greater competition for organ grafts. Pediatric patients with...
UNLABELLED
The success of orthotopic liver transplantation as a life-saving treatment has led to new indications and a greater competition for organ grafts. Pediatric patients with acute liver-related crises can benefit from orthotopic liver transplantation, but organ availability in the limited time can be a major obstacle. Crossing ABO blood group barriers could increase the organs available to such patients.
METHODS
From November 2010 to June 2015, 176 children aged 0.2-to18 y were transplanted in the King Faisal Specialist Hospital and Research Center. Out of those, 19 children were transplanted across blood group barriers (ABO incompatible). The underlying diseases were biliary atresia (n = 6); progressive familial intrahepatic cholestasis type 2 (n = 4); Crigler-Najjar syndrome (n = 3); hepatoblastoma (n = 2); and urea cycle disorder, Caroli disease, cryptogenic cirrhosis, and neonatal sclerosing cholangitis (n = 1 each). Immunosuppression consisted of basiliximab, mycophenolate, tacrolimus, and steroids. Pretransplant prophylactic plasmapheresis, high-dose immunoglobulins, and rituximab were not administered.
RESULTS
The grafts were from living donors (n = 17) and deceased donors (n = 2). Living donor morbidity was nil. The recipient median age was 21 mo (5-70 mo). After a median follow-up of 44 mo, 2 recipients (10%) died because of sepsis, 1 because of uncontrolled acute myeloid leukemia. The overall rejection rate was 7%, and no grafts were lost because of antibody-mediated rejection (AMR). HLA matching was 3.8 of 6 (A, B, DR), and there were 2 patients presented with acute cellular rejection, 1 patient with AMR, and 1 patient with biliary strictures.
CONCLUSIONS
ABO incompatible liver transplantation is a feasible and life-saving option even with antibody and B-cell depletion-free protocol without increasing the risks for AMR. We speculate that this excellent result is most likely because of presence of relatively low titer ABO isoagglutinins and the high HLA match compatibility caused by habit of longstanding interfamilial marriages as typical of Saudi Arabia.
PubMed: 36479277
DOI: 10.1097/TXD.0000000000001353 -
Experimental and Clinical... Aug 2013To compare the efficacy and safety of thymoglobulin compared with basiliximab in patients who had kidney transplants and are at high risk for acute rejection and delayed... (Comparative Study)
Comparative Study
OBJECTIVES
To compare the efficacy and safety of thymoglobulin compared with basiliximab in patients who had kidney transplants and are at high risk for acute rejection and delayed graft function.
MATERIALS AND METHODS
A retrospective review of patients who had 1 or more risk factors for acute rejection and delayed graft function and who were given either thymoglobulin or basiliximab for induction therapy. Incidences of acute rejection, antibody-treated acute rejection, delayed graft function, chronic rejection, cancer, infection, leucopenia, and thrombocytopenia were compared between thymoglobulin and basiliximab groups. Serum creatinine levels within 1 year and long-term graft and patient survival also were compared.
RESULTS
A total of 327 patients were included. Incidences of acute rejection, antibody-treated acute rejection, delayed graft function, and chronic rejection were significantly lower in the thymoglobulin group than in the basiliximab group (P < .05). Serum creatinine levels were lower in the thymoglobulin group on postoperative days 7, 14, and 30 (P < .05). There were no statistically significant differences regarding long-term graft and patient survival, cancer, or total infection rate between the groups. Incidences of Cytomegalovirus infection, leucopenia, and thrombocytopenia were significantly higher in the thymoglobulin group (P < .05).
CONCLUSIONS
Thymoglobulin may improve short-term outcomes, compared with basiliximab, in patients who had kidney transplants and are at high risk for acute rejection and delayed graft function. However, long-term outcomes are similar with thymoglobulin and basiliximab.
Topics: Acute Disease; Adult; Antibodies, Monoclonal; Antilymphocyte Serum; Basiliximab; Biomarkers; Chi-Square Distribution; China; Chronic Disease; Creatinine; Delayed Graft Function; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Incidence; Kaplan-Meier Estimate; Kidney Transplantation; Male; Middle Aged; Recombinant Fusion Proteins; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome
PubMed: 23121641
DOI: 10.6002/ect.2012.0103 -
Medicine Dec 2023Heart transplantation (HT) has become the preferred treatment for end-stage heart disease, but postoperative complications such as infection still threaten the prognosis... (Observational Study)
Observational Study
Heart transplantation (HT) has become the preferred treatment for end-stage heart disease, but postoperative complications such as infection still threaten the prognosis of HT patients. Basiliximab can help minimize immune rejection. However, there is a lack of relevant information to compare the prognosis of different immunosuppression regimens. This study aimed to investigate the risk factors associated with death and infection after HT surgery. We also provide some insightful information on the administration of basiliximab to improve the prognosis of HT patients. In total, 70 patients were included in this retrospective observational study. All participants underwent primary HT and were administered immunosuppressive agents postoperatively. Of these, 38 received additional basiliximab. There was a 6-month follow-up period after HT during which clinical outcomes were monitored. Logistic regression and cox-proportional hazard regression analyses were performed to determine the relationship between basiliximab use and the clinical outcomes of HT. Logistic regression analysis revealed that basiliximab use (odds ratio [OR] = 0.07, P = .014) was an independent risk factor for death after HT. d-Dimer (OR = 9.05, P = .002) and basiliximab use (OR = 0.15, P = .004) were independent risk factors for death after HT. Moreover, patients treated with basiliximab had shorter hospital lengths of stay (23.58 ± 13.89 vs 39.41 ± 24.43, P = .001) and intensive care unit lengths of stay (4.76 ± 2.85 vs 11.25 ± 5.79, P < .001). Furthermore, patients administered basiliximab had lower rates of death (1 [5.4%] vs 9 [28.1%], P = .007) and infection (6 [15.8%] vs 19 [59.4%], P < .001). The postoperative survival rate (hazard ratio 0.08, 95% confidence interval 0.01-0.65, P = .018) and survival against infection (hazard ratio 0.24, 95% confidence interval 0.09-0.64, P = .004) were significantly higher among patients receiving basiliximab treatment than among those not receiving treatment. Our study showed that basiliximab use was closely associated with the rate of postoperative death and infection after HT. HT patients with additional basiliximab administration as immunosuppressive treatment had a better clinical prognosis.
Topics: Humans; Basiliximab; Heart Transplantation; Immunosuppressive Agents; Postoperative Complications; Retrospective Studies
PubMed: 38065924
DOI: 10.1097/MD.0000000000036504 -
Journal of Medicine and Life 2009Thymoglobulin has a proven safety and efficacy profile both as treatment of acute rejection and as induction therapy in organ transplantation. The most common adverse... (Review)
Review
Thymoglobulin has a proven safety and efficacy profile both as treatment of acute rejection and as induction therapy in organ transplantation. The most common adverse events associated with Thymoglobulin are cytokine release syndrome, thrombocytopenia, and lymphopenia. Results of early studies showed an increased rate of cytomegalovirus disease associated with Thymoglobulin treatment, but recent studies indicate that routine administration of modern antiviral prophylaxis can reduce this risk. More research comparing Thymoglobulin with basiliximab will help individualize regimens by matching the choice of induction agent with the risk profile of each transplant recipient. The proven efficacy and safety profile of Thymoglobulin provides an excellent starting point for future investigations. Horse ATG (hATG) or Thymoglobulin + Cyclosporine are an efficacious treatment for aplastic anemia. Due to its higher potency Thymoglobulin may be superior to hATG, but further studies are required for confirmation. GvHD prophylaxis with Thymoglobulin may result in less acute and chronic GvHD, lower TRM, improved survival and quality of life in myeloablative or reduced intensity conditioning protocols in patients receiving hematopoietic stem cells from related or unrelated donors. Attributable to its polyclonal nature, Thymoglobulin provides multifaceted immunomodulation suggesting that its use should be included in the immunosuppressant therapeutic armamentarium to help reduce the incidence of organ rejection and GvHD, and for treatment of aplastic anemia.
Topics: Anemia, Aplastic; Animals; Antibodies, Monoclonal; Antilymphocyte Serum; Graft Rejection; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Myelodysplastic Syndromes; Receptors, Interleukin-2
PubMed: 20112478
DOI: No ID Found -
Clinical and Experimental Hepatology Sep 2021Post-liver transplantation (LTx) bone diseases have been poorly investigated. The frequency of bone diseases (osteopenia and osteoporosis) after LTx is unknown.
INTRODUCTION
Post-liver transplantation (LTx) bone diseases have been poorly investigated. The frequency of bone diseases (osteopenia and osteoporosis) after LTx is unknown.
AIM OF THE STUDY
To define prevalence and risk factors of bone disorders following LTx.
MATERIAL AND METHODS
This prospective study was conducted on 100 consecutive adult patients who underwent living donor liver transplantation (LDLT) at the National Liver Institute (NLI) and survived longer than a year. Bone mineral density (BMD) was evaluated by dual-energy X-ray absorption (DEXA), as well as other pre- and postoperative risk factors.
RESULTS
The frequencies of osteopenia and osteoporosis were found to be 14% and 8% among post-LTx patients. Seven recipients of the osteoporotic group were males, with mean age, and body mass index (BMI) before and after LTx 49.5 ±7.4 years, 24.1 ±4.7 kg/m and 22.8 ±1.5 kg/m, respectively. A significant association between hepatitis C virus (HCV)-related cirrhosis, liver disease severity according to Child-Turcotte-Pugh (CTP) score, and alcoholism with decreased post-LTx BMD was substantiated ( < 0.05, 0.006). Post-LTx development of diabetes mellitus (DM), weight gain, use of corticosteroids and basiliximab all significantly affected decreased post-LTx BMD ( < 0.05). However, binary regression revealed that post-LTx occurrence of DM ( = 0.012, odds ratio [OR] = 0.099), the severity of liver disease ( = 0.023, OR = 0.217), and HCV ( = 0.011, OR = 0.173) are the main independent predictors of metabolic bone disease (MBD) occurrence one year after LTx.
CONCLUSIONS
Post-LTx bone disorders are not infrequent complications and should be more considered in those with HCV-related severe liver disease or developed DM after LTx.
PubMed: 34712830
DOI: 10.5114/ceh.2021.109412