A systematic review to identify whether perfusate biomarkers produced during hypothermic machine perfusion can predict graft outcomes in kidney transplantation
Transplant International. 2020;[record in progress]
There is good evidence to support the use of Hypothermic Machine Perfusion (HMP) over static cold storage as the favoured preservation method for deceased donor kidneys. However, the utility of HMP as a tool to assess the viability of kidneys for transplant is unclear. There is a need to determine whether perfusate biomarkers produced during HMP can predict post-transplant outcomes and assess the suitability of organs for transplantation. Three different Databases (MEDLINE, Embase, Transplant Library) were screened to 31 May 2019. Articles were included if a relationship was reported between one or more perfusate biomarkers and post-transplant outcomes. Studies were assessed and graded for methodological quality and strength of evidence. Glutathione S-transferase was the most promising biomarker for predicting delayed graft function, but its predictive ability was at best moderate. Analysis of primary non-function rates was challenging due to low occurrence rates and small sample sizes. Existing studies are limited in quality and have not yielded biomarkers for kidneys undergoing HMP that are able to predict post-transplant outcomes with sufficient accuracy to support routine clinical use. Further studies with larger samples and more robust methodology are needed.
Comparing preferences of physicians and patients regarding the allocation of donor organs: A systematic review
Transplant Rev (Philadelphia). 2020;[record in progress]:100515
In order to improve the demand-supply-mismatch in transplantation medicine, policy makers have to think about adapting existing legal frameworks for donor organ allocation. This study aims to systematically review preferences of physicians as well as patients in the field of transplantation medicine. PubMed, Web of Science, EBSCO and PsycINFO were searched from January 2000 to December 2018 without language restrictions. Fourteen publications were identified, six aiming at physicians, seven focusing on patients and one on both groups. The criteria used in these studies to elicit preferences can be grouped into six different main categories, all deriving from the general principle of equality: "Effectiveness/Benefit", "Medical urgency", "Own fault", "Social value", "Medical background" and "Socio-demographic status". Whilst patients on the one hand show a high demand for equal access, outcome maximization and punishment for damaging behaviors, they would still allocate organs to people with very low survival chances. Physicians decide against equal access to transplantation in cases where clinical evidence is weighed more heavily, e.g. in the cases of ethnicity and sex. Also, they seem more informed regarding the involvement of medical factors and give less importance to those with uncertain effects on transplantation outcome, such as tissue or blood group match. It is important to continuously monitor preferences of all involved stakeholders in order to achieve fair and accessible transplantation systems.
Measurement of health-related quality of life in pediatric organ transplantation recipients: a systematic review of the PedsQL transplant module
Quality of Life Research. 2020;[record in progress]
OBJECTIVE To collect and assess the extant empirical literature assessing disease-specific health-related quality of life (HRQOL) in pediatric transplant recipients using the PedsQL 3.0 Transplant Module (PedsQL-TM) assessment. STUDY DESIGN A systematic search and review procedure was conducted of research reporting use and results of the PedsQL-TM with samples of pediatric heart, liver, kidney, and lung transplantation. Searches were conducted in nine scholarly databases and two additional sources to identify unpublished research. Multiple reviewers screened studies meeting inclusion criteria in accordance with PRISMA guidelines. RESULTS A final sample of nine studies reported findings for the PedsQL-TM with pediatric organ transplant recipients. Most studies relied on either kidney or liver transplant recipients from single pediatric transplant centers. Factor validity of the PedsQL-TM and inter-rater reliability (IRR) between patients and parents have not been adequately determined. Internal consistency reliability was found as acceptable or excellent across multiple studies. PedsQL-TM scores were found to vary with other HRQOL issues, yet few studies examined their association with medication adherence or posttransplant health outcomes. CONCLUSIONS With the goal of enhancing and sustaining HRQOL in pediatric organ transplant recipients, the need for a psychometrically valid and reliable measure of transplant-specific HRQOL is apparent. Research on the PedsQL-TM supports the promise of this measure although future efforts should be taken to examine measurement issues such as factor validity and IRR. Assessing transplant-specific HRQOL in these patients is paramount for their care and appropriate decision-making by patients, families, and the transplant team.
Photodynamic therapy for the prevention and treatment of Actinic Keratosis/Squamous cell carcinoma in solid organ transplant recipients: A systematic review and meta-analysis
Journal of the European Academy of Dermatology & Venereology. 2020;34(2):251-259
Solid organ transplant recipients (sOTR) are at an increased risk of developing cutaneous cancers, especially squamous cell carcinoma (SCC). Photodynamic therapy (PDT) for the prevention and treatment of actinic keratosis (AK)/SCC in sOTR is increasingly prescribed given the increase in solid organ transplantations performed worldwide. PDT has added advantages of superior cosmetic outcomes and good safety profile compared to conventional surgical methods and other topical therapies. We aim to evaluate the role of PDT in the prevention and treatment of AK/SCC in sOTRs. The Cochrane Library, PubMed and Embase Database were searched. Articles reporting PDT outcomes amongst sOTR with or without AK/SCC at baseline were selected. We classified the studies into two categories: (1)PDT as prevention measure and (2)treatment of AK/SCC in sOTR. Primary outcome for the prevention category was three-year incidence of AK/SCC and complete response (CR) of lesions after PDT exposure in the treatment category. Secondary outcomes were cosmesis and adverse reaction in both categories. Pooled results were expressed as risk difference (RD) with corresponding 95% confidence interval (95% CI). Twelve out of 641 articles met our eligibility criteria, out of which 4 RCTs reported the preventive effect of AK/SCC and another 5 RCTs reported the treatment effect of PDT in sOTR. One RCT did not report absolute number of lesions at baseline/end of study for results to be pooled in the quantitative analysis. The remaining three studies were cohort studies reporting treatment and preventive effect of PDT in sOTR. PDT group had a lower incidence as a preventive measure with pooled RD of 0.14(95% CI 0.08-0.19). The CR in PDT was higher in the treatment group with a pooled RD of 0.77(95% CI 0.6-0.94) and 0.50 (95% CI 0.22-0.79) in pre-divided lesional areas and number of lesions respectively. In conclusion, PDT is efficacious for prevention and treatment of AK/SCC in sOTRs. This article is protected by copyright. All rights reserved.
New possibilities on transplanting kidneys from hepatitis C virus positive donors: a Systematic Review
Transplant Rev (Philadelphia). 2020;34(2):100532
CYP3A5 gene polymorphisms and their impact on dosage and trough concentration of tacrolimus among kidney transplant patients: a systematic review and meta-analysis
Pharmacogenomics Journal. 2020;[record in progress]:06
Tacrolimus is an immunosuppressive drug widely used in kidney transplantation. Cytochrome P450 3A5 (CYP3A5) protein is involved in tacrolimus metabolism. Single nucleotide polymorphism in the CYP3A5 gene (6986A>G) results in alteration in metabolic activity of CYP3A5 protein which eventually affects the tacrolimus concentration. Patients with CYP3A5 expresser genotypes (A/A *1/*1 and A/G *1/*3) metabolize tacrolimus more rapidly than CYP3A5 nonexpressers (G/G *3/*3). We performed meta-analysis to estimate the effect of CYP3A5 polymorphism on the trough concentration-dose ratio (Co/D) and risk of renal allograft rejection with similar post-transplant periods and Asian vs. European populations. Our results showed that the tacrolimus Co/D ratio is significantly lower in CYP3A5 expresser group as compared with nonexpresser in Asian as well as in European populations at any post-transplant period (p < 0.00001). No significant association was found with renal allograft rejection episodes between expressers and nonexpressers in European populations (OR: 1.12; p = 0.47). Interestingly, Asian population (with expresser genotypes) and patients after 3 years post-transplantation (with expresser genotypes) have a higher risk of rejection (OR: 1.62; p < 0.05), (OR: 1.68; p < 0.05), respectively. This could be due to high prevalence of expresser genotypes in Asian population. Few tacrolimus-based studies are identified with long-term graft survival. There is a need to have more studies looking for long-term graft survival in expresser as well as no-expresser groups especially in Asian populations who have high frequency of CYP3A5 functional genotype.
Prevalence of active tuberculosis infection in transplant recipients: A systematic review and meta-analysis
Microbial Pathogenesis. 2020;139:103894
INTRODUCTION Tuberculosis (TB) is considered as a serious complication of organ transplant; therefore, the detection and appropriate treatment of active TB infection is highly recommended for the reduction of mortality in the future. The aim of this review was to conduct a systematic review and meta-analysis assessing the prevalence of active TB infection in transplant recipients (TRs). MATERIAL AND METHODS Electronic databases, including MEDLINE (via PubMed), SCOPUS and Web of Science were searched up to December 24, 2017. The prevalence of active TB was estimated using the random effects meta-analysis. Heterogeneity was evaluated by subgroup analysis. Data were analyzed by STATA version 14. RESULTS The pooled prevalence of post-transplant active TB was estimated 3% [95% CI: 2-3]. The pooled prevalence of active TB in different transplant forms was as follows: renal,3% [95% CI: 2-4]; stem cell transplant (SCT), 1% [95% CI: 0-3]; lung, 4% [95% CI: 2-6]; heart, 3% [95% CI: 2-4]; liver, 1% [95% CI: 1], and hematopoietic stem cell transplant (HSCT), 2% [95% CI: 1-3]. The prevalence of different clinical presentations of TB was as follows: pulmonary TB (59%; 95% CI: 54-65), extra pulmonary TB (27%; 95% CI: 21-33), disseminated TB (15%; 95% CI: 12-19) and miliary TB (8%; 95% CI: 4-13). The pooled prevalence of different diagnostic tests was as follows: chest X-ray, 57% [95% CI, 46-67]; culture, 56% [95% CI, 45-68]; smear, 49% [95% CI, 40-58]; PCR, 43% [95% CI, 40-58]; histology, 26% [95% CI, 20-32], and tuberculin skin test, 19% [95% CI, 10-28]. CONCLUSION A high suspicion level for TB, the early diagnosis and the prompt initiation of therapy could increase the survival rates among SOT patients. Overall, renal and lung TRs appear to have a higher predisposition for acquiring TB than other type of recipients. Monitoring of the high-risk recipients, prompt diagnosis, and appropriate treatment are required to manage TB infection among TRs especially in endemic areas.
Systematic Review of the Safety of Immune Checkpoint Inhibitors Among Kidney Transplant Patients
KI Reports. 2020;5(2):149-158
Introduction: Kidney transplant (Ktx) recipients are excluded from clinical trials of immune checkpoint inhibitors. The aim of this systematic review was to assess the safety of immune checkpoint inhibitors among Ktx patients. Methods: A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through April 2019. We included studies that reported outcomes of Ktx recipients who received immune checkpoint inhibitors for cancer treatment. Outcomes of interest were allograft rejection and/or allograft failure. Results: Twenty-seven articles with a total of 44 Ktx patients treated with immune checkpoint inhibitor were identified. Of 44 Ktx patients, 18 were reported to have acute rejection. Median time from immune checkpoint inhibitors to acute rejection diagnosis was 24 (interquartile range, 10-60) days. Reported types of acute allograft rejection were cellular rejection (33%), mixed cellular and antibody-mediated rejection (17%), and unspecified type (50%). Fifteen (83%) had allograft failure and 8 (44%) died. Three patients had a partial remission (17%), 1 patient achieved cancer response (6%), and 5 patients had stable disease (28%). Conclusion: The findings of our study raise awareness of the increased risk for acute allograft rejection/failure following immune checkpoint inhibitors for cancer treatment among Ktx patients, in particular with programmed cell death 1 (PD-1) inhibitors. Future large-scale clinical studies are required to appraise the pathogenesis and plan optimal balanced therapy that helps sustain graft tolerance.
The role of soluble B cell-activating factor in further stratifying the risk of antibody-mediated rejection post-renal transplant: A meta-analysis
International Immunopharmacology. 2020;79:106059
BACKGROUND We conducted a meta-analysis to evaluate the predictive value of serum soluble B cell-activating factor (sBAFF) for antibody-mediated rejection (ABMR), which remains controversial. METHODS Systematic literature search was performed in PubMed, EMBASE, Scopus, Cochrane Library, Web of Science and three Chinese databases. Studies of any relevant design were included. Random and fixed-effects meta-analytical models were used. Study quality, publication bias, and heterogeneity were assessed. This study was registered with PROSPERO (CRD42019109198). RESULTS Nine observational studies were included in the meta-analysis, including 1302 cases (median NOS quality score = 8, range 6-8). The incidence of ABMR was significantly higher in the high sBAFF group than in the low sBAFF level group (Risk ratio [RR] 2.04 [95% CI 1.52-2.74], I2 = 26%, P < 0.01, N = 1014). The subgroup analysis showed that regardless of pre-transplant donor-specific antibody (DSA) status, the high sBAFF level group still had a significantly higher incidence of ABMR. sBAFF was not associated with the risk of TCMR. The sBAFF level was significantly higher in the anti-HLA-antibody (+) group than in anti-HLA-antibody (-) patients before or after kidney transplantation (Standardized mean difference [SMD] 0.43 [0.29-0.56], P < 0.01, I2 = 34%, N = 1001). CONCLUSION sBAFF is a promising biomarker to further stratify the risk of ABMR post-renal transplant.
Efficacy and safety of ketoconazole combined with calmodulin inhibitor in solid organ transplantation: A systematic review and meta-analysis
Journal of Clinical Pharmacy & Therapeutics. 2020;45(1):29-34
WHAT IS KNOWN AND OBJECTIVE Calcineurin inhibitors (CNIs) can significantly improve the results of solid organ transplantation regarding graft and patient survival. However, the high cost, chronic nephrotoxicity and other side effects are major challenges for the long-term use of these drugs. Ketoconazole can significantly increase the plasma concentration of CNIs by inhibiting the activity of the cytochrome P450 enzyme. The combination of ketoconazole-CNIs can reduce the cost of medication for patients by reducing the dosage of CNIs, but its safety is still controversial. Therefore, this study was designed to assess the safety and efficacy of this combination. METHODS We performed a systematic literature search in PubMed, Embase, Cochrane Library and clinicaltrials.gov for randomized controlled trials on ketoconazole and CNI (cyclosporin or tacrolimus) co-administration in solid organ transplantation. Two authors independently selected studies, assessed the risk of bias and extracted data. The meta-analysis was performed in RevMan 5.3 provided by the Cochrane Collaboration. PROSPERO registration number: CRD42019118796. RESULTS AND DISCUSSION Five relevant trials with 326 patients were included. Compared with the controls, ketoconazole combined with CNIs can significantly reduce the dose of CNIs in patients receiving solid organ transplantation (WMD = -203.04 mg/day; 95% CI: -310.51 to -95.57, P = .0002). There was no significant difference in serum creatinine between the experimental group and the control group (WMD = -0.19 mg/mL; 95% CI: -0.52 to 0.14, P = .26). In addition, there was no significant difference in the number of rejections between the two groups (OR = 0.58; 95% CI: 0.27 to 1.22, P = .15). WHAT'S NEW AND CONCLUSION The co-administration of ketoconazole and CNIs can significantly reduce the dose of CNIs. This combination may be safely used as a CNI-sparing agent from the time of solid organ transplantation with low-dose ketoconazole, based on the findings of this review.