Background
Non‐adherence to immunosuppressant therapy is a significant concern following a solid organ transplant, given its association with graft failure. Adherence to immunosuppressant therapy is ...a modifiable patient behaviour, and different approaches to increasing adherence have emerged, including multi‐component interventions. There has been limited exploration of the effectiveness of interventions to increase adherence to immunosuppressant therapy.
Objectives
This review aimed to look at the benefits and harms of using interventions for increasing adherence to immunosuppressant therapies in solid organ transplant recipients, including adults and children with a heart, lung, kidney, liver and pancreas transplant.
Search methods
We searched the Cochrane Kidney and Transplant Register of Studies up to 14 October 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
Selection criteria
All randomised controlled trials (RCTs), quasi‐RCTs, and cluster RCTs examining interventions to increase immunosuppressant adherence following a solid organ transplant (heart, lung, kidney, liver, pancreas) were included. There were no restrictions on language or publication type.
Data collection and analysis
Two authors independently screened titles and s of identified records, evaluated study quality and assessed the quality of the evidence using the GRADE approach. The risk of bias was assessed using the Cochrane tool. The ABC taxonomy for measuring medication adherence provided the analysis framework, and the primary outcomes were immunosuppressant medication initiation, implementation (taking adherence, dosing adherence, timing adherence, drug holidays) and persistence. Secondary outcomes were surrogate markers of adherence, including self‐reported adherence, trough concentration levels of immunosuppressant medication, acute graft rejection, graft loss, death, hospital readmission and health‐related quality of life (HRQoL). Meta‐analysis was conducted where possible, and narrative synthesis was carried out for the remainder of the results.
Main results
Forty studies involving 3896 randomised participants (3718 adults and 178 adolescents) were included. Studies were heterogeneous in terms of the type of intervention and outcomes assessed. The majority of studies (80%) were conducted in kidney transplant recipients. Two studies examined paediatric solid organ transplant recipients. The risk of bias was generally high or unclear, leading to lower certainty in the results. Initiation of immunosuppression was not measured by the included studies.
There is uncertain evidence of an association between immunosuppressant medication adherence interventions and the proportion of participants classified as adherent to taking immunosuppressant medication (4 studies, 445 participants: RR 1.09, 95% CI 0.95 to 1.20; I² = 78%). There was very marked heterogeneity in treatment effects between the four studies evaluating taking adherence, which may have been due to the different types of interventions used. There was evidence of increasing dosing adherence in the intervention group (8 studies, 713 participants: RR 1.14, 95% CI 1.03 to 1.26, I² = 61%). There was very marked heterogeneity in treatment effects between the eight studies evaluating dosing adherence, which may have been due to the different types of interventions used. It was uncertain if an intervention to increase immunosuppressant adherence had an effect on timing adherence or drug holidays. There was limited evidence that an intervention to increase immunosuppressant adherence had an effect on persistence.
There was limited evidence that an intervention to increase immunosuppressant adherence had an effect on secondary outcomes. For self‐reported adherence, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the proportion of participants classified as medically adherent to immunosuppressant therapy (9 studies, 755 participants: RR 1.21, 95% CI 0.99 to 1.49; I² = 74%; very low certainty evidence). Similarly, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the mean adherence score on self‐reported adherence measures (5 studies, 471 participants: SMD 0.65, 95% CI ‐0.31 to 1.60; I² = 96%; very low certainty evidence). For immunosuppressant trough concentration levels, it is uncertain whether an intervention to increase adherence to immunosuppressant medication increases the proportion of participants who reach target immunosuppressant trough concentration levels (4 studies, 348 participants: RR 0.98, 95% CI 0.68 to 1.40; I² = 40%; very low certainty evidence). It is uncertain whether an intervention to increase adherence to immunosuppressant medication may reduce hospitalisations (5 studies, 460 participants: RR 0.67, 95% CI 0.44 to 1.02; I² = 64%; low certainty evidence). There were limited, low certainty effects on patient‐reported health outcomes such as HRQoL. There was no clear evidence to determine the effect of interventions on secondary outcomes, including acute graft rejection, graft loss and death. No harms from intervention participation were reported.
Authors' conclusions
Interventions to increase taking and dosing adherence to immunosuppressant therapy may be effective; however, our findings suggest that current evidence in support of interventions to increase adherence to immunosuppressant therapy is overall of low methodological quality, attributable to small sample sizes, and heterogeneity identified for the types of interventions. Twenty‐four studies are currently ongoing or awaiting assessment (3248 proposed participants); therefore, it is possible that findings may change with the inclusion of these large ongoing studies in future updates.
Little is known regarding the molecular phenotype of kidneys with AKI because biopsies are performed infrequently. However, all kidney transplants experience acute injury, making early kidney ...transplants an excellent model of acute injury, provided the absence of rejection, because donor kidneys should not have CKD, post-transplant biopsies occur relatively frequently, and follow-up is excellent typically. Here, we used histopathology and microarrays to compare indication biopsies from 26 transplants with acute injury with 11 pristine protocol biopsies of stable transplants. Kidneys with acute injury showed increased expression of 394 transcripts associated with the repair response to injury, including many epithelium-like injury molecules tissue, remodeling molecules, and inflammation molecules. Many other genes also predicted the phenotype, including the acute injury biomarkers HAVCR1 and IL18. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score in kidneys with acute injury correlated with reduced graft function, future renal recovery, brain death, and need for dialysis, but not with future graft loss. In contrast, histologic features of acute tubular injury did not correlate with function or with the molecular changes. Thus, the transcripts associated with repair of injury suggest a massive coordinated response of the kidney parenchyma to acute injury, providing both an objective measure for assessing the severity of injury in kidney biopsies and validation for many biomarkers of AKI.
Background
Living donation is not only a method to increase access to kidney transplantation but can also offer superior outcomes. We report the experience of the living donor (LD) program in the ...Republic of Ireland and explore reasons why potential donors do not proceed to live donation.
Methods
Retrospective cohort study of all potential donors from January 2000 to March 2014 who presented wishing to undergo donor work‐up and their subsequent outcomes.
Results
A total of 956 donors for 496 recipients contacted the live kidney donation program of which 883 potential donors proceeded to the initial stage of assessment. The donor dropout rate at this stage was 64.2% (614/956 potential donors did not proceed to further evaluation). Thereafter, 269 (28.1%) donors underwent further assessment by the multidisciplinary team. In total, 93 (9.7%) donors were declined following this assessment with 176 (18.4%) donors ultimately proceeding to live kidney donation. The major reason for declining a donor was a medical contraindication (n = 63, 67.7%). In term of recipients, 54.2% (n = 269/496) had a potential donor proceed for further assessment of which 65.4% (n = 176/269) ultimately proceeding to live donation.
Conclusion
Further evaluation of the declined donor group is warranted to allow for expansion of the LD program.
Full text
Available for:
DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
We report 2 cases of apixaban use as prophylaxis against thromboembolism in the nephrotic syndrome (NS), and review the existing literature on direct-acting oral anticoagulant (DOAC) use in this ...scenario. Our cases appear to be the first reported use of apixaban as prophylaxis against thromboembolism in NS. We report our systematic review of the existing literature on direct-acting oral anticoagulant (DOAC) use in NS, and discuss theoretical issues relevant to their therapeutic use in this clinical scenario. We searched electronic databases such as OVID, EMBASE, PubMed, and CENTRAL, DARE. The search to identify studies and the application of inclusion and exclusion criteria was performed in duplicate independently. We identified 1 pilot randomized study, 3 case reports, and 3 conference proceedings abstracts relating to DOAC use in NS. These reports all pertain to the treatment of clinically evident thrombosis in NS with rivaroxaban, edoxaban, and dabigatran rather than prophylaxis against thrombosis. Although the existing literature on DOAC use in NS is limited, initial preliminary experience appears promising.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
It is often quoted that while short‐term graft survival in kidney transplantation has improved in recent years, it has not translated into a commensurate improvement in long‐term graft ...survival. We considered whether this was true of the entire experience of the national kidney transplant program in Ireland. A retrospective analysis of the National Kidney Transplant Service (NKTS) database was undertaken to investigate patient and graft survival for all adult first deceased donor kidney transplant recipients in Ireland, 1971–2015. Three thousand two hundred and sixty recipients were included in this study. Kaplan–Meier methods were used to estimate survival at each time period post transplant for the various eras of transplantation. Uncensored graft survival has improved over the course of the program in Ireland at various time points despite risk factors for graft failure progressively increasing over successive eras. For example the graft survival at 15 years post transplant has increased from 10% in 1971–1975 to 45% by 1996–2000. Ireland has experienced a progressive improvement in long‐term graft survival following kidney transplantation. Whether these trends are attributable to biological or nonbiological factors is unclear but likely involves a combination of both.
Background
New-onset diabetes after transplant (NODAT) confers risk of diabetes-related complications as well as a threat to graft function and overall patient survival. The reported incidence of ...NODAT varies from 14 to 37% in renal transplant recipients worldwide; however, NODAT is yet to be studied in the Irish renal transplant population.
Aims
Primary aims of this project were to estimate the incidence, to determine associated risk factors and to assess the long-term consequences of NODAT on graft survival and patient survival in the Irish renal transplant population.
Methods
Retrospective data collection of 415 renal transplant recipients over a 12-year period was performed to record presence of NODAT, patient characteristics and perioperative management. Preoperative screening was reviewed in a subgroup of patients to determine concordance with the International Consensus Guidelines. Statistical analysis was performed using Kaplan-Meier survival functions estimating NODAT detection over time, graft and patient survival. Risk factor association was determined using Cox proportional-hazards models.
Results
NODAT incidence was 10.2% in the first 5 years of post-transplant. Risk factors for developing NODAT were recipient age and body weight. Risk of NODAT was highest in the first year of post-transplant and conferred decreased patient survival; however, it did not significantly affect graft survival. Only seven patients of a subgroup of 21 patients who developed NODAT had preoperative testing for diabetes.
Conclusions
NODAT incidence in the Irish renal transplant population is slightly below international figures. This project has highlighted current deficits in the national transplant guidelines for the detection of NODAT and NODAT-related risk factors.
The Kidney Donor Risk Index (KDRI)/Kidney Donor Profile Index (KDPI) is relied upon for donor organ allocation in the USA, based on its association with graft failure in time-to-event models. ...However, the KDRI/KDPI has not been extensively evaluated in terms of predictive metrics for graft failure and allograft estimated glomerular filtration rate (eGFR) outside of the USA.
We performed a retrospective analysis of outcomes in the Irish National Kidney Transplant Service Registry for the years 2006-13. Associations of the KDRI/KDPI score with eGFR at various time points over the follow-up and ultimate graft failure were modelled.
A total of 772 patients had complete data regarding KDRI/KDPI calculation and 148 of these allografts failed over the follow-up. The median and 25-75th centile for KDRI/KDPI was 51 (26-75). On repeated-measures analysis with linear mixed effects models, the KDRI/KDPI (fixed effect covariate) associated with eGFR over 5 years: eGFR = -0.25 (standard error 0.02; P < 0.001). The variability in eGFR mathematically accounted for by the KDRI/KDPI score was only 21%. The KDRI/KDPI score did not add significantly to graft failure prediction above donor age alone (categorized as > and <50 years of age) when assessed by the categorical net reclassification index.
In this cohort, while the KDRI/KDPI was predictive of eGFR over the follow-up, it did not provide additive discrimination above donor age alone in terms of graft failure prediction. Therefore it is unlikely to help inform decisions regarding kidney organ allocation in Ireland.
Background
The survival of incident dialysis patients’ end-stage kidney disease in some European and American has been reported to improve in modern era compared to earlier periods. However, in ...Ireland, this has not been well documented.
Aim
To investigate the survival outcomes of incident end-stage kidney failure dialysis patients in a tertiary center over a 24-year period, 1993–2017.
Methods
A retrospective analysis was carried out utilizing the Beaumont Hospital Renal Database. Consecutive adults with incident dialysis were analyzed. Kaplan-Meier methods and the estimated mean survival times were used to evaluate survival at successive 4-year periods of time.
Results
In total, 2106 patients were included, of whom 830 underwent subsequent renal transplantation during follow-up. During the study period, from 1993 up to 2017, the mean patients’ age increased from 56.3 ± 17.4 in 1993–1996 to 60.6 ± 18.3 in 2014–2017. There was an overall decrement in mortality over successive time intervals which were mirrored by the improvements in median survival after commencement of dialysis treatment from 6.14 years during 1993–1996 to 8.01 years during 2009–2012. Patients’ survival has steadily improved, with the 5-year survival has risen over time, by almost 15%. This positive signal persisted and became more pronounced after adjusting Kaplan-Meier curve to age, where the 5-year survival estimates were exceeding 80% in 2014–2017.
Conclusion
Survival rates among incident dialysis patients have improved progressively between 1993 and 2017 in Beaumont Hospital in Dublin, Ireland. The factors which led to this improvement are not entirely clear, but likely to be multifactorial.
This study aims to report a case of accelerated metabolism of voriconazole in a patient with cerebral aspergillosis.
A 36-year-old woman developed cerebral aspergillosis after immunosuppressive ...treatment for suspected atypical hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. She was treated with voriconazole using therapeutic drug monitoring to guide dosing. After an initial high level, her dose was reduced, but over the following weeks, she required several dose increases in order to achieve a voriconazole level within the target range. The patient's dose requirements eventually stabilized at 700 mg twice daily. Cimetidine and omeprazole were added in an effort to inhibit the metabolism of voriconazole.
The metabolism of voriconazole is known to be highly variable among different patients depending on pharmacogenetic factors; however, an increasing rate of voriconazole metabolism in a single patient over time is not well recognized. Therapeutic drug monitoring of voriconazole in this case facilitated the use of large doses while controlling for toxicity.
This case is further evidence of autoinduction in voriconazole metabolism. Therapeutic drug monitoring of voriconazole is useful in detecting variation in a patient's metabolism of voriconazole over time.
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