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Pediatric Transplantation Aug 2024BK polyomavirus (BKV) DNAemia is a challenging infectious complication after kidney transplant (KT). Reduction of immunosuppression is the mainstay of management, and...
BACKGROUND
BK polyomavirus (BKV) DNAemia is a challenging infectious complication after kidney transplant (KT). Reduction of immunosuppression is the mainstay of management, and tacrolimus is often the first immunosuppressive medication adjusted upon the diagnosis of BKV DNAemia. This study aimed to evaluate the impact of a new institutional protocol with lower target tacrolimus levels on BKV DNAemia, allograft rejection, and de novo donor-specific antibodies (dnDSA) among pediatric KT recipients.
METHODS
We conducted a retrospective chart review of all KT episodes between January 2013 and December 2018. The new protocol with lower target tacrolimus levels was implemented in March 2015. One hundred twenty-seven patients were included in primary analysis. All patients received induction with basiliximab and methylprednisolone and were maintained on a steroid-based immunosuppressive regimen.
RESULTS
In the post-intervention cohort, cumulative incidence of BKV DNAemia at 100 days (13.4% vs. 17.8%, p = .605) and 18 months post-KT (34.1% vs. 26.7%, p = .504) was not significantly different from the pre-intervention cohort. Biopsy-proven rejection rate did not change. However, we observed a trend toward earlier development of dnDSA in the post-intervention cohort using the Kaplan-Meier survival analysis (log-rank p = .06). Younger recipient age at the time of transplant was found to slightly increase the risk of BKV DNAemia (OR: 1.09, 95% CI [1.01, 1.16], p = .024). There was an association between BKV DNAemia and biopsy-proven rejection of any type (OR: 2.77, 95% CI [1.26, 6.23], p = .012), especially acute T-cell-mediated rejection grade 1A and above (OR: 2.95, 95% CI [1.06, 8.30], p = .037), after adjusted for recipient age at the time of transplant.
CONCLUSIONS
Targeting lower tacrolimus levels did not decrease the incidence of BKV DNAemia within 100 days or 18 months post-KT, nor did it increase the risk of biopsy-proven rejection among pediatric KT recipients in our center. However, there was a trend toward earlier development of dnDSA, which may portend worse long-term graft outcome post-KT. Our findings highlight the need for individualized immunosuppressive regimens based on immunologic and infectious risk factors and the importance of implementing innovative biomarkers to guide therapy and improve outcomes.
Topics: Humans; Kidney Transplantation; Retrospective Studies; BK Virus; Male; Female; Graft Rejection; Child; Tacrolimus; Immunosuppressive Agents; Polyomavirus Infections; Adolescent; Tumor Virus Infections; Child, Preschool; DNA, Viral; Infant; Postoperative Complications
PubMed: 38808701
DOI: 10.1111/petr.14791 -
Clinical Transplantation Jun 2024Patients undergoing heart transplants are at risk of rejection which can have significant morbidity and mortality. Induction immunosuppression at the time of transplant... (Comparative Study)
Comparative Study
BACKGROUND
Patients undergoing heart transplants are at risk of rejection which can have significant morbidity and mortality. Induction immunosuppression at the time of transplant reduces the early risk and has additional benefits. The induction agent of choice within our program was changed from rabbit antithymocyte-globulin (rATG) to basiliximab, so it was necessary to evaluate whether this had any impact on patient outcomes.
OBJECTIVES
Our primary objective was to describe rejection, infection, and other outcomes in adult heart transplant patients at the University of Alberta Hospital in Edmonton, Canada.
METHODS
This study was a nonrandomized, retrospective cohort study.
RESULTS
Sixty-three patients were included with median ages 50 years versus 54 years. More female patients received rATG (20% vs. 42.4%). The most common indication for transplant in both cohorts was ICM (63.3% vs. 57.6%). Patients who received rATG had significantly higher PRA (0% vs. 43%, p < .001). Acute rejection episodes were similar between basiliximab and rATG at 3 months (16.7% vs. 15.1%; p = 1.0) and 6-months (30.0% vs. 18.1%; p = .376). Infections were not statistically different with basiliximab compared to rATG at 3-months, 43.3% vs. 63.6% and at 6-months 60.0% vs. 66.7%). There were no fatalities in either group.
CONCLUSIONS
Our study did not demonstrate differences in rejection with basiliximab compared to rATG. Mortality did not differ, but basiliximab-treated patients had fewer infections and infection-related hospitalizations than those treated with rATG. Larger studies with longer durations are needed to more completely describe the differences in rejection and infectious outcomes.
Topics: Humans; Basiliximab; Female; Male; Heart Transplantation; Middle Aged; Retrospective Studies; Recombinant Fusion Proteins; Graft Rejection; Antilymphocyte Serum; Immunosuppressive Agents; Adult; Follow-Up Studies; Antibodies, Monoclonal; Graft Survival; Prognosis; Risk Factors; Postoperative Complications; Aged; Immunosuppression Therapy
PubMed: 38804609
DOI: 10.1111/ctr.15332 -
Pediatric Transplantation Jun 2024We hypothesized that alemtuzumab use is safe in pediatric kidney transplant recipients (KTRs) with equivalent long-term outcomes compared to other induction agents.
Alemtuzumab induction is associated with decreased hospitalization rates in pediatric kidney transplant: A UNOS data review for safety and outcomes with common induction regimens.
BACKGROUND
We hypothesized that alemtuzumab use is safe in pediatric kidney transplant recipients (KTRs) with equivalent long-term outcomes compared to other induction agents.
METHODS
Using pediatric kidney transplant recipient data in the UNOS database between January 1, 2000, and June 30, 2022, multivariate logistic regression, multivariable Cox regression, and survival analyses were utilized to estimate the likelihoods of 1st-year and all-time hospitalizations, acute rejection, CMV infection, delayed graft function (DGF), graft loss, and patient mortality among recipients of three common induction regimens (ATG, alemtuzumab, and basiliximab).
RESULTS
There were no differences in acute rejection or graft failure among induction or maintenance regimens. Basiliximab was associated with lower odds of DGF in deceased donor recipients (OR 0.77 [0.60-0.99], p = .04). Mortality was increased in patients treated with steroid-containing maintenance (HR 1.3 [1.005-1.7] p = .045). Alemtuzumab induction correlated with less risk of CMV infection than ATG (OR 0.76 [0.59-0.99], p = .039). Steroid-containing maintenance conferred lower rate of PTLD compared to steroid-free maintenance (HR 0.59 [0.4-0.8] p = .001). Alemtuzumab was associated with less risk of hospitalization within 1 year (OR 0.79 [0.67-0.95] p = .012) and 5 years (HR 0.54 [0.46-0.65] p < .001) of transplantation. Steroid maintenance also decreased 5 years hospitalization risk (HR 0.78 [0.69-0.89] p < .001).
CONCLUSIONS
Pediatric KTRs may be safely treated with alemtuzumab induction without increased risk of acute rejection, DGF, graft loss, or patient mortality. The decreased risk of CMV infections and lower hospitalization rates compared to other agents make alemtuzumab an attractive choice for induction in pediatric KTRs, especially in those who cannot tolerate ATG.
Topics: Humans; Alemtuzumab; Kidney Transplantation; Child; Male; Hospitalization; Female; Graft Rejection; Immunosuppressive Agents; Adolescent; Child, Preschool; Basiliximab; Infant; Graft Survival; Antilymphocyte Serum; Treatment Outcome; Retrospective Studies; Delayed Graft Function; Cytomegalovirus Infections
PubMed: 38767019
DOI: 10.1111/petr.14783 -
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 -
Clinical Transplantation May 2024Induction therapy (IT) utility in heart transplantation (HT) remains contested. Commissioned by a clinical-practice guidelines panel to evaluate the effectiveness and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Induction therapy (IT) utility in heart transplantation (HT) remains contested. Commissioned by a clinical-practice guidelines panel to evaluate the effectiveness and safety of IT in adult HT patients, we conducted this systematic review and network meta-analysis (NMA).
METHODS
We searched for studies from January 2000 to October 2022, reporting on the use of any IT agent in adult HT patients. Based on patient-important outcomes, we performed frequentist NMAs separately for RCTs and observational studies with adjusted analyses, and assessed the certainty of evidence using the GRADE framework.
RESULTS
From 5156 publications identified, we included 7 RCTs and 12 observational studies, and report on two contemporarily-used IT agents-basiliximab and rATG. The RCTs provide only very low certainty evidence and was uninformative of the effect of the two agents versus no IT or one another. With low certainty in the evidence from observational studies, basiliximab may increase 30-day (OR 1.13; 95% CI 1.06-1.20) and 1-year (OR 1.11; 95% CI 1.02-1.22) mortality compared to no IT. With low certainty from observational studies, rATG may decrease 5-year cardiac allograft vasculopathy (OR .82; 95% CI .74-.90) compared to no IT, as well as 30-day (OR .85; 95% CI .80-.92), 1-year (OR .87; 95% CI .79-.96), and overall (HR .84; 95% CI .76-.93) mortality compared to basiliximab.
CONCLUSION
With low and very low certainty in the synthetized evidence, these NMAs suggest possible superiority of rATG compared to basiliximab, but do not provide compelling evidence for the routine use of these agents in HT recipients.
Topics: Humans; Heart Transplantation; Graft Rejection; Immunosuppressive Agents; Network Meta-Analysis; Prognosis; Evidence-Based Medicine; Graft Survival; Practice Guidelines as Topic; Induction Chemotherapy
PubMed: 38716786
DOI: 10.1111/ctr.15326 -
Transplantation Proceedings May 2024Hematopoietic stem cell transplant (HSCT) is the treatment of choice in various hematologic diseases, and kidney transplantation (KTx) is the best therapy for end-stage...
Hematopoietic stem cell transplant (HSCT) is the treatment of choice in various hematologic diseases, and kidney transplantation (KTx) is the best therapy for end-stage kidney disease. Chronic kidney disease (CKD) occurs relatively often after both types of transplantations. Anemia after both HSCT and KTx may be due to CKD and other reasons. This study aimed to assess the prevalence of anemia to CKD in 156 prevalent patients after HSCT and 80 after KTx. According to the World Health Organization's definition (hemoglobin <13 g/dL for men and <12 g/dL for women), the prevalence of anemia in the studied cohort after HSCT was 13% in women and 35% in men and for those after KTx, it was29% in men and 11%. Anemia in KTx was found in 46% of patients, whereas CKD was present in 53%. After HSCT, anemia was associated with CKD in 56% of women and 17% of men. In KTx, anemia and CKD was diagnosed in 21% of patients. Patients with anemia after KTx had significantly lower glomerular filtration rate (GFR), hemoglobin, and significantly higher creatinine levels. Age was related to the estimated GFR (eGFR; r = -0.39, P < .001) in patients who underwent HSCT and had anemia. In patients without anemia, age was negatively related to eGFR (r = -0.56, P < .001) and the hemoglobin-to-platelet count (r = 0.62, P < .001). In KTx, hemoglobin was related to eGFR (r = 0.35, P < .001), and age was related to eGFR (r = -0.20, P < .05). The type of induction therapy immunosuppressive regimen (anti-thymocyte globulin vs basiliximab vs no induction) did not affect the prevalence of anemia in the KTx population studied. Anemia is relatively common in CKD after HSCT. In both CKD and coexistent anemia, nephrology referral is to be considered to optimize therapy, including nephroprotection.
PubMed: 38705734
DOI: 10.1016/j.transproceed.2024.03.028 -
Clinical Nephrology May 2024The relative safety and efficacy of early steroid withdrawal in kidney transplant patients after basiliximab compared to anti-thymocyte globulin (ATG) induction therapy...
BACKGROUND AND OBJECTIVES
The relative safety and efficacy of early steroid withdrawal in kidney transplant patients after basiliximab compared to anti-thymocyte globulin (ATG) induction therapy is unknown. We aimed to compare kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction from the United Network for Organ Sharing (UNOS) database.
MATERIALS AND METHODS
We conducted a retrospective cohort analysis of the UNOS database and included first kidney transplant recipients who received ATG or basiliximab induction therapy. We compared graft and patient outcomes in those who received steroid maintenance and those who were discharged off steroids.
RESULTS
Of 106,061 patients, 25,344 (86.7%) received basiliximab induction and were maintained on steroids (B-Sm), and 3,880 (13.3%) were on a steroid-free regimen (B-Sf). Graft failure rate was significantly higher in the B-Sf compared to B-Sm at 1-year (4.1 vs. 1.8%, p < 0.001), 3-year (6.0 vs. 4.3%, p < 0.001) and 5-year follow-up (7.7 vs. 6.4%, p = 0.0004). The mortality rate was significantly higher in B-Sf at 1-year (3.3 vs. 2.4%, p = 0.0005), 3-year (7.6 vs. 5.5%, p < 0.001) and 5-year follow-up (11.5 vs. 8.8%, p < 0.001) when compared to the B-Sm. 76,837 recipients received ATG induction therapy, 51,745 (72.4%) were on steroid maintenance therapy (A-Sm) and 25,092 (32.6%) were on a steroid-free regimen (A-Sf). The graft failure rate was significantly higher in A-Sf compared to A-Sm at 1-year follow-up (2.6 vs. 2.3%, p = 0.0006), however, there was no difference at 3-year (5.0 vs. 5.0%, p = 0.53) or 5-year follow-up (7.2 vs. 8.1%, p = 0.17). There was no difference in mortality rates between A-Sf vs. A-Sm at 1 year (2.5 vs. 2.4%, p = 0.98) and at 3 years (5.5 vs. 5.4%, p = 0.45), respectively.
CONCLUSION
Patients who were maintained on steroids after basiliximab induction had better 5-year allograft survival and patient survival compared to those who were not maintained on steroids. However, steroid maintenance conferred no additional benefit after ATG induction and was associated with higher mortality.
PubMed: 38699983
DOI: 10.5414/CN111033 -
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 -
Value in Health Regional Issues Apr 2024To evaluate cost-effective pharmacological treatment in adult kidney transplant recipients from the perspective of the Colombian health system.
OBJECTIVES
To evaluate cost-effective pharmacological treatment in adult kidney transplant recipients from the perspective of the Colombian health system.
METHODS
A decision tree model for the induction phase and a Markov model for the maintenance phase were built. A review of the clinical literature was conducted to extract probabilities, and the life-years were used as the outcome. Costs were calculated using the administrative databases. The evaluating treatment schemes are organized by groups of evidence with direct comparisons.
RESULTS
In the induction phase, anti-thymocyte immunoglobulin+ methylprednisolone is dominant, more effective, and less expensive, compared with basiliximab+methylprednisolone. In the maintenance phase, azathioprine (AZA) is dominant in contrast to mycophenolate mofetil (MFM) both with cyclosporine (CIC)+ corticosteroids (CE); CIC is dominant relative to sirolimus (SIR) and tacrolimus (TAC) (both with MFM+CE or AZA+CE), and TAC is dominant compared with SIR (in addition with MFM+CE or mycophenolate sodium [MFS]+CE); MFM is dominant in relation to MFS and everolimus, and SIR is more effective MFM but it does not exceed the threshold (in sum with TAC+CE); MFS and MFM are dominant relative to everolimus, and SIR is more effective than MFM, but it does not exceed the threshold (in addiction with CIC+CE); MFM is dominant in relation to TAC (in sum with SIR+CE), and CIC+AZA+CE is dominant in relation to TAC+MFM+CE.
CONCLUSIONS
The base-case results for all evidence groups are consistent with the different sensitivity analyses.
PubMed: 38663057
DOI: 10.1016/j.vhri.2024.02.001