METHODS: This study reports baseline data from a longitudinal study that was conducted at a hospital in Vietnam. KTRs aged ≥18 years and >3 months post-transplantation were recruited. Assessments included sociodemographic and blood biomarkers. Dietary intake was estimated from 24-hour recalls. A Short Form-36 Health Survey, comprising physical (PCS) and mental component summaries (MCS), was administered to assess QoL. Multivariate linear regression models were performed.
RESULTS: The study included 106 patients (79 men) with a mean age of 43.2 years (± 11.9). Mean duration after kidney transplantation was 28.5 months (± 14.9). Patients with MetS had 6.43 lower PCS score (P < .05) and 3.20 lower MCS score (P < .05) than their counterparts without MetS. Calcium intake (β = -0.01; 95% CI, -0.03 to 0.00) and inadequate protein (β = -14.8; 95% CI, -23 to -6.65) were negatively associated with PCS score. MCS score was negatively associated with calcium intake (β = -0.02; 95% CI, -0.04 to -0.01) and inadequate protein intake (β = -15.1; 95% CI, -24.3 to -5.86), and positively associated with fat intake (β = 0.43, 95% CI, 0.02-0.85).
CONCLUSIONS: MetS and poor dietary intake are independently associated with the QoL of KTRs. Nutritional intervention plans developed specifically for the recipients will improve dietary intake, reduce the incidence of MetS, and help enhance QoL.
METHODS: A retrospective audit of heart transplant recipients (n = 87) treated with tacrolimus was performed. Relevant data were collected from the time of transplant to discharge. The concordance of tacrolimus dosing and monitoring according to hospital guidelines was assessed. The observed and software-predicted tacrolimus concentrations (n = 931) were compared for the first 3 weeks of oral immediate-release tacrolimus (Prograf) therapy, and the predictive performance (bias and imprecision) of the software was evaluated.
RESULTS: The majority (96%) of initial oral tacrolimus doses were guideline concordant. Most initial intravenous doses (93%) were lower than the guideline recommendations. Overall, 36% of initial tacrolimus doses were administered to transplant recipients with an estimated glomerular filtration rate of <60 mL/min/1.73 m despite recommendations to delay the commencement of therapy. Of the tacrolimus concentrations collected during oral therapy (n = 1498), 25% were trough concentrations obtained at steady-state. The software displayed acceptable predictions of tacrolimus concentration from day 12 (bias: -6%; 95%confidence interval, -11.8 to 2.5; imprecision: 16%; 95% confidence interval, 8.7-24.3) of therapy.
CONCLUSIONS: Tacrolimus dosing and monitoring were discordant with the guidelines. The Bayesian forecasting software was suitable for guiding tacrolimus dosing after 11 days of therapy in heart transplant recipients. Understanding the factors contributing to the variability in tacrolimus pharmacokinetics immediately after transplant may help improve software predictions.
METHODS: We performed a systematic review and meta-analysis of available literature regarding NTM infection in children and adults receiving allogeneic HSCT.
RESULTS: We identified 56 articles eligible for the analysis. Among 15 studies, describing 15,798 allogeneic HSCT, we estimated a prevalence of 1.26% (95% CI 0.72, 1.93) of NTM after transplant. Analysis of 175 patients with NTM infection showed a median time of diagnosis of 318 days after HSCT, an increased prevalence in adults (82.9%), and a most frequent pulmonary involvement (44%). Comparison between children and adults revealed an earlier post-transplant disease onset (median 130 days vs 287 days) and most frequent non-pulmonary presentation in children. A vast heterogeneity of therapeutic approach reflected the lack of universal recommendations regarding drug combination and duration of therapy. Overall, NTM-related mortality accounted for 33% in this systematic review.
CONCLUSION: Although rare, NTM infections can complicate post-transplant course with a high mortality rate in children and adults. The lack of prospective studies and guidelines prevents identification of risk factors and therapeutic recommendations.
AIM: We aimed to report the largest number of COVID-19-positive cases in KTR in a single center and to discuss their demographics, management, and evolution.
METHODS: We enrolled all the two thousand KTR followed up in our center in Kuwait and collected the data of all COVID-19-positive KTR (104) from the start of the outbreak till the end of July 2020 and have reported the clinical features, management details, and both patient and graft outcomes.
RESULTS: Out of the one hundred and four cases reported, most of them were males aged 49.3 ± 14.7 years. Eighty-two of them needed hospitalization, of which thirty-one were managed in the intensive care unit (ICU). Main comorbidities among these patients were hypertension in 64.4%, diabetes in 51%, and ischemic heart disease in 20.2%. Management strategies included anticoagulation in 56.7%, withdrawal of antimetabolites in 54.8%, calcineurin inhibitor (CNI) withdrawal in 33.7%, the addition of antibiotics in 57.7%, Tocilizumab in 8.7%, and antivirals in 16.3%. During a follow-up of 30 days, the reported number of acute kidney injury (AKI) was 28.7%, respiratory failure requiring oxygen therapy 46.2%, and overall mortality rate was 10.6% with hospital mortality of 13.4% including an ICU mortality rate of 35.5%.
CONCLUSION: Better outcome of COVID-19-positive KTR in our cohort during this unremitting stage could be due to the younger age of patients and early optimized management of anticoagulation, modification of immunosuppression, and prompt treatment of secondary bacterial infections. Mild cases can successfully be managed at home without any change in immunosuppression.
METHODS: The MEDLINE and EMBASE databases, as well as the reference lists of all articles, were searched to identify population PK models of tacrolimus developed from adult transplant recipients published from the inception of the databases to 29 February 2020.
RESULTS: Of the 69 studies identified, 55% were developed from kidney transplant recipients and 30% from liver transplant recipients. Most studies (91%) investigated the oral immediate-release formulation of tacrolimus. Few studies (17%) explained the effect of drug-drug interactions on tacrolimus PK. Only 35% of the studies performed an external evaluation to assess the generalizability of the models. Studies related variability in tacrolimus whole blood clearance among transplant recipients to either cytochrome P450 (CYP) 3A5 genotype (41%), days post-transplant (30%), or hematocrit (29%). Variability in the central volume of distribution was mainly explained by body weight (20% of studies).
CONCLUSION: The effect of clinically significant drug-drug interactions and different formulations and brands of tacrolimus should be considered for any future tacrolimus population PK model development. Further work is required to assess the generalizability of existing models and identify key factors that influence both initial and maintenance doses of tacrolimus, particularly in heart and lung transplant recipients.
AIM AND METHODS: This study used microcosting methods to determine the cost and health outcomes of living and deceased donor kidney transplantation in adult and pediatric recipients. The perspective used was from the Ministry of Health Malaysia. Cost-effectiveness measures were cost per life year (LY) and cost per quality-adjusted LYs. The time horizon was the lifetime of the transplant recipient from transplant to death.
RESULTS: Records of 206 KT recipients (118 adults and 88 children) were obtained for microcosting. In adults, discounted cost per LY was US $8609(Malaysian Ringgit [RM]29 482) and US $13 209(RM45 234) for living-donor kidney transplant (LKT) and deceased donor kidney transplant (DKT), respectively, whereas in children, it was US $10 485(RM35 905) and US $14 985(RM51 317), respectively. Cost per quality-adjusted LY in adults was US $8826 (RM30 224) for LKT and US $13 592(RM46 546) for DKT. Total lifetime discounted costs of adult transplants were US $119 702 (RM409 921) for LKT, US $147 152 (RM503 922) for DKT. Total costs for pediatric transplants were US $154 841(RM530 252) and US $159 313(RM545 566) for the 2 categories respectively.
CONCLUSIONS: Both LKT and DKT are economically favorable for Malaysian adult and pediatric patients with ESRD and result in improvement in quality of life.
METHODS: Data from heart transplant recipients (n = 87) administered the oral immediate-release formulation of tacrolimus (Prograf®) were collected. Routine drug monitoring data, principally trough concentrations, were used for model building (n = 1099). A published tacrolimus model was used to inform the estimation of Ka , V2 /F, Q/F and V3 /F. The effect of concomitant azole antifungal use on tacrolimus CL/F was quantified. Fat-free mass was implemented as a covariate on CL/F, V2 /F, V3 /F and Q/F on an allometry scale. Subsequently, stepwise covariate modelling was performed. Significant covariates influencing tacrolimus CL/F were included in the final model. Robustness of the final model was confirmed using prediction-corrected visual predictive check (pcVPC). The final model was externally evaluated for prediction of tacrolimus concentrations of the fourth dosing occasion (n = 87) from one to three prior dosing occasions.
RESULTS: Concomitant azole antifungal therapy reduced tacrolimus CL/F by 80%. Haematocrit (∆OFV = -44, P transplant recipients, considering the tacrolimus-azole antifungal interaction was developed. Prospective evaluation is required to assess its clinical utility to improve patient outcomes.
METHODOLOGY: This is a retrospective cohort study recruiting all kidney transplant recipients in South Australia from January 2010 till December 2018. Following that, the incidence of blood transfusion within one week post-operatively were traced (transfusion group). The outcomes were compared with all other transplant recipients (non-transfusion group). Recipient's demographic, donor characteristics and immunological risk profiles were obtained from the transplant unit database, while the biopsy report, history of blood transfusion, latest serum creatinine and follow-up status was gathered from the electronic medical system (OASIS). The HLA-DSA and HLA-Ab results were collected from the NOMS database. Finally, the survival data were merged with the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry for South Australia recipients graft survival.
RESULTS: A total of 699 patients were eligible for analysis. The mean age was 50.64 ± 13.23 years old. There were more elderly (>65 years old) and females who needed transfusion. The majority had glomerulonephritis as the primary disease. There was no statistical difference in donor characteristics, cold ischemic time and immunological risk between the transfusion and non-transfusion group. There was no difference in the development of de novo HLA-DSA, HLA-Ab and rejection episodes between the group and the results were consistent in a model adjusted for all potential confounders. Median graft survival in days between the transfusion vs non-transfusion group was 1845 IQR (961,2430) and 1250 IQR (672,2013).
CONCLUSION: Blood transfusion under strong immunosuppressive cover within a one-week post-operative period is safe with no significant association with the development of de novo HLA-DSA, HLA-Ab or clinical rejection.
Methods: This was a single-centre, retrospective cohort study evaluating posaconazole suspension pre-emptive therapy in LTx recipients between January 2009 and December 2015.
Results: Forty-two LTx recipients were prescribed posaconazole suspension pre-emptively. Aspergillus fumigatus was the most commonly isolated fungal organism. Of the patients receiving posaconazole suspension as the initial antifungal post-LTx, 93% had eradication of colonization at 6 months after commencing therapy. In contrast, only 61% had eradication of fungal colonization when posaconazole suspension was administered following initial therapy with voriconazole. Posaconazole suspension appeared to be well tolerated, although one case was curtailed following concern about abnormal liver function and another due to nausea/vomiting. TDM was performed in 37 patients. The initial median (IQR) trough plasma concentration ( C min ) following 400 mg twice-daily posaconazole suspension was 0.78 (0.46-1.19) mg/L. Doses beyond 800 mg daily did not appear to result in a higher median C min.
Conclusions: Early initiation of posaconazole suspension pre-emptive therapy in LTx recipients appears to be well tolerated and may potentially afford favourable clinical outcomes.
METHODS: This retrospective study was performed on all KTRs ≥18 years of age at our center from January 1, 2006 to December 31, 2015, who were prescribed diltiazem as tacrolimus-sparing agent. Blood tacrolimus trough level (TacC0) and other relevant clinical data for 70 eligible KTRs were reviewed.
RESULTS: The dose of 1 mg tacrolimus resulted in a median TacC0 of 0.83 ± 0.52 ng/mL. With the introduction of a 90-mg/d dose diltiazem, there was a significant TacC0 increase to 1.39 ± 1.31 ng/mL/mg tacrolimus (P < .01). A further 90-mg increase in diltiazem to 180 mg/d resulted in a further increase of TacC0 to 1.66 ± 2.58 ng/mL/mg tacrolimus (P = .01). After this, despite a progressive increment of every 90-mg/d dose diltiazem to 270 mg/d and 360 mg/d, there was no further increment in TacC0 (1.44 ± 1.15 ng/mL/mg tacrolimus and 1.24 ± 0.94 ng/mL/mg tacrolimus, respectively [P < .01]). Addition of 180 mg/d diltiazem reduced the required tacrolimus dose to 4 mg/d, resulting in a cost-savings of USD 2045.92 per year (per patient) at our center. Adverse effects reported within 3 months of diltiazem introduction were bradycardia (1.4%) and postural hypotension (1.4%), which resolved after diltiazem dose reduction.
CONCLUSION: Coadministration of tacrolimus and diltiazem in KTRs appeared to be safe and resulted in a TacC0 increment until reaching a 180-mg/d total diltiazem dose, at which point it began to decrease. This approach will result in a marked savings in immunosuppression costs among KTRs in Malaysia.