Tacrolimus is a cornerstone of posttransplantation immunosuppressive regimens. Despite routine monitoring, the efficacy of its trough concentrations in reflecting drug concentration fluctuations is limited. Intrapatient variability (IPV) emerges as a novel monitoring marker for predicting clinical outcomes. However, understanding the factors affecting IPV and assessing interventions to address it remain enigmatic, posing a conundrum in clinical management.
This systematic review aimed to investigate a spectrum of factors affecting IPV and assess the effect of strategic interventions, thereby charting a course for enhanced clinical stewardship.
We electronically searched of PubMed, Embase, and the Cochrane Library databases for studies investigating factors and interventions affecting IPV up to October 2023. Two reviewers independently screened literature, extracted data, and assessed quality, using RevMan 5.4.1 software for meta-analysis.
A total of 15 randomized controlled trials (RCTs), 34 cohort studies, and 20 self-controlled studies were included. The results indicated that IPV was significantly higher in cytochrome P450 3A5 (CYP3A5) expressers, nonadherent patients, patients taking proton pump inhibitors or statins, and Black or African American recipients, whereas recipients consuming extended-release formulation exhibited lower IPV. Additionally, the participation of pharmacists had a positive effect on improving IPV.
Factors affecting IPV encompassed genotype, formulation, adherence, drug combinations, and ethnicity, with each factor exerting varying degrees of effect. Identifying these factors was crucial for developing targeted intervention strategies. While the participation of pharmacists held a promise in improving IPV, further investigation of interventions such as mobile technology, educational measures to enhance adherence, and personalized dosing regimens was warranted.
Kidney transplantation provides substantial benefits in extending survival and improving quality of life for patients with end-stage renal disease. The incidence of major adverse cardiac events (MACE) increases with a decline of kidney function in patients with chronic kidney disease. After kidney transplantation, the incidence of MACE remains high. The objective of this study was to assess the prognostic significance of pre-transplant single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in kidney transplant recipients.
A systematic literature search was performed between January 1st 2015 and March 26th 2024 in PubMed, EMBASE, Web of Science and The Cochrane Library to identify the prognostic value of SPECT MPI for developing MACE (primary outcome) and mortality (secondary outcome) in kidney transplant recipients (PROSPERO CRD42020188610). Risk of bias was assessed. Meta-analyses and subgroup analyses were performed using random-effects models.
Six studies comprising 2090 SPECT MPI scans were included. Abnormal SPECT MPI scans were associated with an increased risk of MACE post-transplantation (HR 1.62, 95% CI 1.27–2.06, p < 0.001). Subgroup analyses showed consistent findings across various patient populations and methodological differences. Sensitivity analyses supported the robustness of our findings.
Current evidence showed that pre-transplant SPECT MPI has significant prognostic value in identifying kidney transplant candidates at risk for MACE post-transplantation. Integrating SPECT MPI into preoperative assessments might enhance risk stratification and guide clinical decision-making. Prospective studies are needed to refine risk prediction models.
The treatment of refractory CMV is often associated with high toxicity. Maribavir (MBV) is a novel oral antiviral, known for its favourable safety profile in fragile patients. We describe a case of CMV disease with end organ damage following kidney transplantation at high risk, for recipient-donor serological mismatch. A 54-year-old female with history of obesity, hypertension, and chronic kidney disease, on prednisone and tacrolimus after kidney transplantation in November 2022, soon after developed primary CMV infection, treated with Valganciclovir and CMV Ig. In January 2023 the patient presented with fever and dyspnea. Pulmonary miliary opacities and right-upper lobe consolidation were found at CT-scan along with CMV-DNA positivity on BAL and serum. Lung biopsy confirmed CMV infection. Antiviral was switched to Ganciclovir. Despite initial benefit, fever and respiratory failure happened 8 days later, leading to intubation at day 15. Due to slow decrease serum CMV-DNA and detection of UL97 mutation, conferring resistance to valganciclovir and ganciclovir, the patient was started on foscarnet and letermovir. She was extubated after a gradual respiratory improvement and discharged from ICU to rehabilitation department with HFNC; reduction in serum CMV-DNA, but persistently elevated CMV-DNA on BAL were documented. At week 8, MBV was started and letermovir continued, for a 8 weeks course, without notable adverse effects. Respiratory function improved but soon after septic shock occurred. A bone marrow biopsy resulted in lymphoma, without indications for treatment: the patient developed coma and died 6 months after admission. MBV has recently been approved in Europe for treatment of R/R CMV in HSCT and SOT recipients. MBV showed superior rates of viraemia clearance after 8 weeks compared to SOC, demonstrating also a favourable safety profile with fewer patients discontinuing treatment and being affected by nephrotoxicity and neutropenia. Its main side effects are taste impairment, gastro-intestinal symptoms and asthenia. Based on actual promising perspectives regarding antiviral stewardship, more data are required to corroborate benefit of MBV in terms of toxicity and impact on mortality in highly fragile populations as SOT recipients.
MBV received approval for the treatment of refractory or resistant CMV infections to other antiviral agents. Nevertheless, real-life data on efficacy and safety of MBV are still lacking.
We conducted a narrative review of the current literature on MBV as treatment for CMV infection in kidney transplant recipients to understand clinical characteristics, safety and outcomes of MBV in this population. A search was run on the main scientific databases. 194 papers were identified, of which 188 were excluded by title and abstract evaluation. Subsequently, 6 papers were included. We performed descriptive statistics on the entire study population. The studies included in our analysis showed a higher preva
Although kidney transplantation (KT) is the best treatment option for end-stage kidney disease, long-term complications such as chronic kidney allograft dysfunction and cardiovascular disorders are observed. To decrease these complications, preventive measures must be applied in kidney transplant recipients (KTRs). One of these common measures is the increase of water/fluid intake although this is not evidence-based practice. Indeed, surprisingly very limited studies evaluated the impact of increased water/fluid intake on graft function, with small number of KTRs and short term follow-up. We suggest that the water/fluid intake should be personalized based on baseline graft function, time onset after KT (which water homeostasis changes), presence of hyponatremia and hypervolemia, concomitant medications, and patient willingness. Methods for estimating water/fluid intake (direct measurement, 24-h urine volume measurement, urine osmolarity) has both advantages and drawbacks and the best method has not been identified. Increase of water/fluid intake in specific conditions (in hot, and humid weather, before exercise, during Ramadan fasting) or in distinct KTRs (KTRs with de novo nephrolithiasis, frequent urinary tract infections) is not tested. Furthermore, the relationship between water/fluid intake and major cardiovascular adverse events are not known. There is no doubt that minimum amount of water/fluid intake is necessary for graft function (the amount is not known) but there is no evidence for a particular target level of water/fluid intake. In the current review, we summarize the studies assessing fluid/water intake in KTR, explained the pathophysiologic basis of water disorders in early period of KT and late after KT, elucidate conflicts and unknown issues of water intake in KTRs and suggest future research needs.
There are multiple methods for preventing lymphocele formation after kidney transplantation (KTx). However, lymphoceles still develop in up to one third of patients and the effectiveness of these different methods in preventing lymphocele is not well described. Here, we summarize the current strategies for preventing lymphocele after KTx.
We conducted searches across several literature databases, including Medline (via PubMed), Web of Science, EMBASE, and Cochrane Central. Lymphocele formation after KTx was the outcome of interest. A random-effects model was applied to evaluate pooled estimates, which were presented as hazard ratios (HRs) and odds ratios (ORs), along with the random pooled estimate (ES), 95% confidence interval (95% CI), and P value. We calculated the pooled rate of lymphocele formation after KTx with the following preventive methods: LigaSure, haemostatic materials, prophylactic drainage, ligation, peritoneal fenestration, and bipolar cautery techniques.
The literature search retrieved 87 unique studies after excluding duplicates. Twenty papers reporting on 5445 patients were incorporated in the qualitative analysis. The pooled lymphocele rate was 3.0% (95% CI = 0.6–13.7) for the LigaSure method, 8.3% (95% CI = 6.4–10.7) for drainage, 9.2% (95% CI = 5.9–14.1) for haemostatic materials, 12.2% (95% CI = 9.2–16.1) for ligation, 14.4% (95% CI = 12.0–17.3) for peritoneal fenestration, and 20.5% (95% CI = 10.2–36.8) for bipolar sealing.
Despite preventive methods, the incidence of lymphocele following KTx remains high. The use of LigaSure appears to be the most effective method for preventing lymphocele. However, given the broad range of reported lymphocele rates and lack of control groups, further validation of these findings is necessary.
Cytomegalovirus (CMV) infection remains a significant challenge in solid organ transplantation (SOT). The last international consensus guidelines on the management of CMV in SOT were published in 2018, highlighting the need for revision to incorporate recent advances, notably in cell-mediated immunity monitoring, which could alter the current standard of care. A working group including members from the Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Transplantation (SET), developed consensus-based recommendations for managing CMV infection in SOT recipients. Recommendations were classified based on evidence strength and quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The final recommendations were endorsed through a consensus meeting and approved by the expert panel.
To identify the barriers and facilitators of deceased organ donation among the Muslim community living globally.
A systematic search was undertaken in databases such as CINAHL, Medline with full text, Global Health and PsycINFO via EBSCO; Scopus via Elsevier; Web of Science via Clarivate; and PubMed via US National Library of Medicine National Institute of Health were used to retrieve the studies on the 31st of December 2023. Apart from these databases two other journals, the Saudi Journal of Kidney Diseases and Transplantation, and the Journal of Experimental and Clinical Transplantation were also used to search for relevant studies. Quantitative and qualitative studies that addressed the aim of the present review published from the 30th of April 2008 were included.
Of the 10,474 studies, 95 studies were included in the review. The following five themes were generated based on narrative synthesis: 1) knowledge of organ donation, 2) willingness to donate, 3) community influence, 4) bodily influence, and 5) religious influence. While individuals view organ donation as a noble act, societal influences significantly impact their decision to register. Concerns include religious permissibility, potential misuse for commercial purposes, and the dignity and respect given to the deceased donor's body.
This review finds deceased organ donation decisions in this population are collective, influenced by religious views, and hindered by uncertainty. Interventional studies on strategies to address uncertainty could help us identify best practices for this population to improve deceased organ donation. Rather than an individual approach among this population, a whole-system approach, tailored-made evidence-guided community engagement could improve donation rates.
Measures of patient experience are increasingly valued as key to healthcare quality assessment. We aimed to identify and describe publicly available measures assessing patient-reported experience of solid organ transplantation healthcare, and identify patient groups, healthcare settings, or aspects of patient experience underserved by existing measures.
We systematically searched MEDLINE, Embase, CINAHL, PsycINFO, Cochrane CENTRAL, Scopus and Web of Science from inception to 6th July 2023; supplemented with grey literature searches. Two reviewers independently screened search hits; outputs reporting patient-reported measures of multiple aspects of established solid organ transplantation healthcare were eligible. We abstracted measure context, characteristics, content (i.e., attributes of patient experience assessed), and development and validation processes.
We identified nine outputs reporting eight measures of patient experience; these related only to kidney (n = 5) or liver (n = 3) transplantation, with no available measures relating to heart, lung, pancreas or intestinal transplantation. Of the identified measures, four were specific to solid organ transplant recipients. Measures sought to assess “patient satisfaction” (n = 4) and “patient experience” (n = 4) of healthcare. Measures mapped to between five and 16 of 20 attributes of patient experience, most often Information and education, Communication, and Access to care (all n = 7). Six measures reported a development process, only three reported a validation process.
Publicly available patient-reported measures of organ transplantation healthcare experiences are limited to kidney and liver transplantation. There is heterogeneity in measure context, characteristics, and content, and insufficient clarity concerning how well measures capture the specific experiences of transplant recipients. Formalised measures of patient experience, specific to solid organ transplantation, with transparent reporting of development and validity are needed.
Simultaneous combined transplantation (SCT), i.e. the transplantation of two solid organs within the same procedure, can be required when the patients develop more than one end-stage organ failure. The development of SCT over the last 20 years could only be possible thanks to progress in the surgical techniques and in the perioperative management of patients in an ageing population. Performing such major transplant surgeries from the same donor, in a short amount of time, and in critical pathophysiological conditions, is often considered to be counterbalanced by the immune benefits expected from these interventions. However, SCT includes a wide array of different transplant combinations, with each time a different immunological constellation. Recent research offers new insights into the immune mechanisms involved in these different settings. Progress in the understanding of these immunological intricacies help to address the optimal induction and maintenance immunosuppressive treatment strategies. In this review, we summarize the different immunological benefits according to the type of SCT performed. We also incorporate the main outcomes according to the immunological risk at transplantation, and the deleterious impact of preformed or de novo donor-specific antibodies (DSA) in the different types of SCT. Finally, we propose comprehensive and evidence-based induction and maintenance immunosuppression strategies guided by the type of SCT.