世界移植杂志最新文献

{"title":"Kidney transplantation outcomes: Is it possible to improve when good results are falling down?","authors":"Fernando M Gonzalez, Francisca Del Rocío Gonzalez Cohens","doi":"10.5500/wjt.v14.i3.91214","DOIUrl":"https://doi.org/10.5500/wjt.v14.i3.91214","url":null,"abstract":"<p><p>Famure <i>et al</i> describe that close to 50% of their patients needed early or very early hospital readmissions after their kidney transplantation. As they taught us the variables related to those outcomes, we describe eight teaching capsules that may go beyond what they describe in their article. First two capsules talk about the ideal donors and recipients we should choose for avoiding the risk of an early readmission. The third and fourth capsules tell us about the reality of cadaveric donors and recipients with comorbidities, and the way transplant physicians should choose them to maximize survival. Fifth capsule shows that any mistake can result in an early readmission, and thus, in poorer outcomes. Sixth capsule talks about economic losses of early readmissions, cost-effectiveness of transplantation, and how to improve outcomes and reduce costs by managing a risky patient-portfolio. Seventh capsule argues about knowing your risk behavior to better manage your portfolio; and Eighth capsule about the importance of the center experience in transplanting complex patients. We finish with some lessons of the importance of the transplantation process and the collaboration with other disciplines in order to prevent the conditions that lead to early readmissions.</p>","PeriodicalId":65557,"journal":{"name":"世界移植杂志","volume":"14 3","pages":"91214"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Medicaid expansion on kidney transplantation in the State Oklahoma.","authors":"Hyoshin Kwon, Zoya Sandhu, Zoona Sarwar, Oya M Andacoglu","doi":"10.5500/wjt.v14.i3.92981","DOIUrl":"https://doi.org/10.5500/wjt.v14.i3.92981","url":null,"abstract":"<p><strong>Background: </strong>There is no data evaluating the impact of Medicaid expansion on kidney transplants (KT) in Oklahoma.</p><p><strong>Aim: </strong>To investigate the impact of Medicaid expansion on KT patients in Oklahoma.</p><p><strong>Methods: </strong>The UNOS database was utilized to evaluate data pertaining to adult KT recipients in Oklahoma in the pre-and post-Medicaid eras. Bivariate analysis, Kaplan Meier analysis was used to estimate, and cox proportional models were utilized.</p><p><strong>Results: </strong>There were 2758 pre- and 141 recipients in the post-Medicaid expansion era. Post-expansion patients were more often non-United States citizens (2.3% <i>vs</i> 5.7%), American Indian, Alaskan, or Pacific Islander (7.8% <i>vs</i> 9.2%), Hispanic (7.4% <i>vs</i> 12.8%), or Asian (2.5% <i>vs</i> 8.5%) (<i>P</i> < 0.0001). Waitlist time was shorter in the post-expansion era (410 <i>vs</i> 253 d) (<i>P</i> = 0.0011). Living donor rates, pre-emptive transplants, re-do transplants, delayed graft function rates, kidney donor profile index values, panel reactive antibodies levels, and insurance types were similar. Patients with public insurance were more frail. Despite increased early (< 6 months) rejection rates, 1-year patient and graft survival were similar. In Cox proportional hazards model, male sex, American Indian, Alaskan or Pacific Islander race, public insurance, and frailty category were independent risk factors for death at 1 year. Medicaid expansion was not associated with graft failure or patient survival (adjusted hazard ratio: 1.07; 95%CI: 0.26-4.41).</p><p><strong>Conclusion: </strong>Medicaid expansion in Oklahoma is associated with increased KT access for non-White/non-Black and non-United States citizen patients with shorter wait times. 1-year graft and patient survival rates were similar before and after expansion. Medicaid expansion itself was not independently associated with graft or patient survival outcomes. Ongoing research is necessary to determine the long-term effects of Medicaid expansion.</p>","PeriodicalId":65557,"journal":{"name":"世界移植杂志","volume":"14 3","pages":"92981"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genitourinary tumors and liver transplantation: A comprehensive review.","authors":"Vibor Sesa, Hrvoje Silovski, Nikolina Basic-Jukic, Iva Kosuta, Maja Sremac, Anna Mrzljak","doi":"10.5500/wjt.v14.i3.95987","DOIUrl":"https://doi.org/10.5500/wjt.v14.i3.95987","url":null,"abstract":"<p><p>Liver transplantation is as a crucial therapeutic option for patients with end-stage liver disease, but the persistent organ shortage emphasizes a need to explore unconventional donor sources, including individuals with a history of malignancies. This review investigates the viability of liver donation from individuals with current or past genitourinary malignancies, focusing on renal, prostate and urinary bladder cancers. The rising incidence of urogenital malignancies among potential donors is thought to result from increasing donor age. Analysis of transmission risks reveals low rates of donor-derived cancer transmission, particularly for early-stage renal and prostate cancers. Recipients with a history of genitourinary malignancy pose complex challenges regarding post-transplant immunosuppression and cancer recurrence. Nonetheless, the evidence suggests acceptable outcomes can be achieved with careful patient selection and tailored management strategies. Recommendations for pre-transplant evaluation and post-transplant surveillance are discussed, highlighting the need for individualized approaches in this patient population. Further prospective studies are warranted to refine guidelines and optimize outcomes in liver transplantation for patients with genitourinary malignancies.</p>","PeriodicalId":65557,"journal":{"name":"世界移植杂志","volume":"14 3","pages":"95987"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of hepatitis B immunoglobulin mode of administration on treatment experiences of patients after liver transplantation: Results from an online survey.","authors":"Giorgia Rizza, Kyriaki Glynou, Masha Eletskaya","doi":"10.5500/wjt.v14.i3.90949","DOIUrl":"https://doi.org/10.5500/wjt.v14.i3.90949","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis B immunoglobulin (HBIG) in combination with a potent nucleos(t)ide analog is considered the standard of care for prophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation for HBV-associated disease.</p><p><strong>Aim: </strong>To evaluate patients' satisfaction, preferences, and requirements for subcutaneous (SC), intramuscular (IM), and intravenous (IV) HBIG treatments.</p><p><strong>Methods: </strong>A self-completion, cross-sectional, online, 22-question survey was conducted to examine perceptions and satisfaction with current HBIG treatment in adults receiving HBIG treatment following liver transplantation for HBV-associated disease in France, Italy, and Turkey. Hypothetical HBIG products with different administration modes were evaluated using target product profile assessment and a conjoint (trade-off) exercise.</p><p><strong>Results: </strong>Ninety patients were enrolled; 32%, 17%, and 51% were SC, IM, and IV HBIG users, respectively. Mean duration of treatment was 36.2 months. SC HBIG had the least negative impact on emotional well-being and social life and was perceived as the most convenient, easiest to administer, least painful, and had the highest self-rating of treatment compliance. More IM HBIG users than SC or IV HBIG users reported that administration frequency was excessive (67%, 28%, and 28%, respectively). In the target product profile assessment, 76% of patients were likely to use hypothetical SC HBIG. In the conjoint exercise, administration route, frequency, and duration were key drivers of treatment preferences.</p><p><strong>Conclusion: </strong>Ease, frequency, duration, and side effects of HBIG treatment administration were key drivers of treatment preferences, and SC HBIG appeared advantageous over IM and IV HBIG for administration ease, convenience, and pain. A hypothetical SC HBIG product elicited a favorable response. Patient demographics, personal preferences, and satisfaction with HBIG treatment modalities may influence long-term treatment compliance.</p>","PeriodicalId":65557,"journal":{"name":"世界移植杂志","volume":"14 3","pages":"90949"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matched pair analysis of the effect of longer hypothermic machine perfusion time on kidney transplant outcomes.","authors":"Carlos Verdiales, Luke Baxter, Hyun Ja Lim, Gavin Beck, Michael A Moser","doi":"10.5500/wjt.v14.i3.95233","DOIUrl":"https://doi.org/10.5500/wjt.v14.i3.95233","url":null,"abstract":"<p><strong>Background: </strong>Hypothermic machine perfusion (HMP) has demonstrated benefits in terms of early kidney transplant function compared to static cold storage. While longer preservation times have shown detrimental effects, a previous paired study indicated that longer pump times (the second kidney in a pair) might lead to improved outcomes.</p><p><strong>Aim: </strong>To revisit the prior paired study's somewhat unexpected results by reviewing our program's experience.</p><p><strong>Methods: </strong>A total of 61 pairs of transplant recipients who received kidneys from the same donor (2012-2021) were analyzed. Patients were divided into two groups depending on whether they were transplanted first (K1) or second (K2). Therefore, the patients in each pair had identical donor characteristics, except for time on the pump. Statistical analyses included Kaplan-Meyer analysis and paired tests, including McNemar's test, student's paired <i>t</i>-test, or Wilcoxon's test, as appropriate.</p><p><strong>Results: </strong>The two groups of recipients had similar demographics (age, body mass index, diabetes, time on dialysis, sensitization and retransplants). Cold ischemic times for K1 and K2 were 8.9 (95%CI: 7.9, 9.8) and 14.7 hours (13.7, 15.8) (<i>P</i> < 0.0001), respectively. Overall, K2 had a higher rate of freedom from biopsy-proven acute rejection at 1 year (<i>P</i> = 0.015). Delayed graft function was less common in K2, 12/61 (20%) than in K1, 20/61 (33%) (<i>P</i> = 0.046). Finally, K2 showed a higher graft survival than K1 (<i>P</i> = 0.023).</p><p><strong>Conclusion: </strong>Our results agree with a previous study that suggested possible advantages to longer pump times. Both studies should encourage further research into HMP's potential anti-inflammatory effect.</p>","PeriodicalId":65557,"journal":{"name":"世界移植杂志","volume":"14 3","pages":"95233"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recipient functional status impacts on short and long-term intestinal transplant outcomes in United States adults.","authors":"Sarpong Boateng, Prince Ameyaw, Solomon Gyabaah, Yaw Adjepong, Basile Njei","doi":"10.5500/wjt.v14.i3.93561","DOIUrl":"https://doi.org/10.5500/wjt.v14.i3.93561","url":null,"abstract":"<p><strong>Background: </strong>Recipient functional status prior to transplantation has been found to impact post-transplant outcomes in heart, liver and kidney transplants. However, information on how functional status, before and after transplant impacts post-transplant survival outcomes is lacking.</p><p><strong>Aim: </strong>To investigate the impact of recipient functional status on short and long term intestinal transplant outcomes in United States adults.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study on 1254 adults who underwent first-time intestinal transplantation from 2005 to 2022. The primary outcome was mortality. Using the Karnofsky Performance Status, functional impairment was categorized as severe, moderate and normal. Analyses were conducted using Kaplan-Meier curves and multivariable Cox regression.</p><p><strong>Results: </strong>The median age was 41 years, majority (53.4%) were women. Severe impairment was present in 28.3% of recipients. The median survival time was 906.6 days. The median survival time was 1331 and 560 days for patients with normal and severe functional impairment respectively. Recipients with severe impairment had a 56% higher risk of mortality at one year [Hazard ratio (HR) = 1.56; 95%CI: 1.23-1.98; <i>P</i> < 0.001] and 58% at five years (HR = 1.58; 95%CI: 1.24-2.00; <i>P</i> < 0.001) compared to patients with no functional impairment. Recipients with worse functional status after transplant also had poor survival outcomes.</p><p><strong>Conclusion: </strong>Pre- and post-transplant recipient functional status is an important prognostic indicator for short- and long-term intestinal transplant outcomes.</p>","PeriodicalId":65557,"journal":{"name":"世界移植杂志","volume":"14 3","pages":"93561"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study.","authors":"William Chung, Kevin Wong, Noel Ravindranayagam, Lauren Tang, Josephine Grace, Darren Wong, Danny Con, Marie Sinclair, Avik Majumdar, Numan Kutaiba, Samuel Hui, Paul Gow, Vijayaragavan Muralidharan, Alexander Dobrovic, Adam Testro","doi":"10.5500/wjt.v14.i3.94914","DOIUrl":"https://doi.org/10.5500/wjt.v14.i3.94914","url":null,"abstract":"<p><strong>Background: </strong>Liver transplantation (LT) is a potentially curative therapy for patients with hepatocellular carcinoma (HCC). HCC-recurrence following LT is associated with reduced survival. There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT.</p><p><strong>Aim: </strong>To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC, and patient outcomes following LT.</p><p><strong>Methods: </strong>This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022, from a single Australian centre. Drug use was defined as statin, aspirin or metformin therapy for ≥ 29 days, within 24 months post-LT. A cox proportional-hazards model with time-dependent covariates was used for survival analysis. Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality, HCC-recurrence and HCC-related mortality. Sensitivity analysis was performed to account for immortality time bias and statin dosing.</p><p><strong>Results: </strong>Three hundred and five patients were included in this study, with 253 (82.95%) males with a median age of 58.90 years. Aetiologies of liver disease were 150 (49.18%) hepatitis C, 73 (23.93%) hepatitis B (HBV) and 33 (10.82%) non-alcoholic fatty liver disease (NAFLD). 56 (18.36%) took statins, 51 (16.72%) aspirin and 50 (16.39%) metformin. During a median follow-up time of 59.90 months, 34 (11.15%) developed HCC-recurrence, 48 (15.74%) died, 17 (5.57%) from HCC-related mortality. Statin, aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality [hazard ratio (HR): 1.16, 95%CI: 0.58-2.30; HR: 1.21, 95%CI: 0.28-5.27; HR: 0.61, 95%CI: 0.27-1.36], HCC-recurrence (HR: 0.52, 95%CI: 0.20-1.35; HR: 0.51, 95%CI: 0.14-1.93; HR 1.00, 95%CI: 0.37-2.72), or HCC-related mortality (HR: 0.32, 95%CI: 0.033-3.09; HR: 0.71, 95%CI: 0.14-3.73; HR: 1.57, 95%CI: 0.61-4.04) respectively. Statin dosing was not associated with statistically significant differences in HCC-related outcomes.</p><p><strong>Conclusion: </strong>Statin, metformin or aspirin use was not associated with improved HCC-related outcomes post-LT, in a largely historical cohort of Australian patients with a low proportion of NAFLD. Further prospective, multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.</p>","PeriodicalId":65557,"journal":{"name":"世界移植杂志","volume":"14 3","pages":"94914"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tuberculosis in kidney transplant candidates and recipients.","authors":"Pallavi Prasad, Sourabh Sharma, Subashri Mohanasundaram, Anupam Agarwal, Himanshu Verma","doi":"10.5500/wjt.v14.i3.96225","DOIUrl":"https://doi.org/10.5500/wjt.v14.i3.96225","url":null,"abstract":"<p><p>Tuberculosis (TB) is the leading cause of infectious mortality and morbidity in the world, second only to coronavirus disease 2019. Patients with chronic kidney disease and kidney transplant recipients are at a higher risk of developing TB than the general population. Active TB is difficult to diagnose in this population due to close mimics. All transplant candidates should be screened for latent TB infection and given TB prophylaxis. Patients who develop active TB pre- or post-transplantation should receive multidrug combination therapy of antitubercular therapy for the recommended duration with optimal dose modification as per glomerular filtration rate.</p>","PeriodicalId":65557,"journal":{"name":"世界移植杂志","volume":"14 3","pages":"96225"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation.","authors":"Amr Alnagar, Nekisa Zakeri, Konstantinos Koilias, Rosemary E Faulkes, Rachel Brown, Owen Cain, M Thamara P R Perera, Keith J Roberts, Rebeca Sanabria-Mateos, David C Bartlett, Yuk Ting Ma, Shivan Sivakumar, Shishir Shetty, Tahir Shah, Bobby V M Dasari","doi":"10.5500/wjt.v14.i3.95849","DOIUrl":"https://doi.org/10.5500/wjt.v14.i3.95849","url":null,"abstract":"<p><strong>Background: </strong>Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has a devastating influence on recipients' survival; however, the risk of recurrence is not routinely stratified. Risk stratification is vital with a long LT waiting time, as that could influence the recurrence despite strict listing criteria.</p><p><strong>Aim: </strong>This study aims to identify predictors of recurrence and develop a novel risk prediction score to forecast HCC recurrence following LT.</p><p><strong>Methods: </strong>A retrospective review of LT for HCC recipients at University Hospitals Birmingham between July 2011 and February 2020. Univariate and multivariate analyses were performed to identify recurrence predictors, based on which the novel SIMAP500 (satellite nodules, increase in size, microvascular invasion, AFP > 500, poor differentiation) risk score was proposed.</p><p><strong>Results: </strong>234 LTs for HCC were performed with a median follow-up of 5.3 years. Recurrence developed in 25 patients (10.7%). On univariate analyses, RETREAT score > 3, α-fetoprotein (AFP) at listing 100-500 and > 500, bridging, increased tumour size between imaging at the listing time and explant histology, increase in the size of viable tumour between listing and explant, presence of satellite nodules, micro- and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence, based on which, the SIMAP500 risk score is proposed. The SIMAP500 demonstrated an excellent predictive ability (c-index = 0.803) and outperformed the RETREAT score (c-index = 0.73). SIMAP500 is indicative of the time to disease recurrence.</p><p><strong>Conclusion: </strong>SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence. Risk stratification allows patient-centric post-transplant surveillance programs. Further validation of the score is recommended.</p>","PeriodicalId":65557,"journal":{"name":"世界移植杂志","volume":"14 3","pages":"95849"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dosing strategies for <i>de novo</i> once-daily extended release tacrolimus in kidney transplant recipients based on <i>CYP3A5</i> genotype.","authors":"Adam Diamond, Sunil Karhadkar, Kenneth Chavin, Serban Constantinescu, Kwan N Lau, Oscar Perez-Leal, Kerry Mohrien, Nicole Sifontis, Antonio Di Carlo","doi":"10.5500/wjt.v13.i6.368","DOIUrl":"10.5500/wjt.v13.i6.368","url":null,"abstract":"<p><strong>Background: </strong>Tacrolimus extended-release tablets have been Food and Drug Administration-approved for use in the <i>de novo</i> kidney transplant population. Dosing requi rements often vary for tacrolimus based on several factors including variation in metabolism based on <i>CYP3A5</i> expression. Patients who express <i>CYP3A5</i> often require higher dosing of immediate-release tacrolimus, but this has not been established for tacrolimus extended-release tablets in the <i>de novo</i> setting.</p><p><strong>Aim: </strong>To obtain target trough concentrations of extended-release tacrolimus in <i>de novo</i> kidney transplant recipients according to <i>CYP3A5</i> genotype.</p><p><strong>Methods: </strong>Single-arm, prospective, single-center, open-label, observational study (ClinicalTrials.gov: NCT037 13645). Life cycle pharma tacrolimus (LCPT) orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight. If weight is more than 120% of ideal body weight, an adjusted body weight was used. LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL. Pharmacogenetic analysis of <i>CYP3A5</i> genotype was performed at study conclusion.</p><p><strong>Results: </strong>Mean time to therapeutic tacrolimus trough concentration was longer in <i>CYP3A5</i> intermediate and extensive metabolizers <i>vs CYP3A5</i> non-expressers (6 d <i>vs</i> 13.5 d <i>vs</i> 4.5 d; <i>P</i> = 0.025). Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in <i>CYP3A5</i> intermediate and extensive metabolizers <i>vs CYP3A5</i> non-expressers (16 mg <i>vs</i> 16 mg <i>vs</i> 12 mg; <i>P</i> = 0.010) (0.20 mg/kg <i>vs</i> 0.19 mg/kg <i>vs</i> 0.13 mg/kg; <i>P</i> = 0.018). <i>CYP3A5</i> extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to <i>CYP3A5</i> intermediate metabolizers and non-expressers (7.98 ng/mL <i>vs</i> 9.18 ng/mL <i>vs</i> 10.78 ng/mL; <i>P</i> = 0 0.008). No differences were identified with regards to kidney graft function at 30-d post-transplant. Serious adverse events were reported for 13 (36%) patients.</p><p><strong>Conclusion: </strong>Expression of <i>CYP3A5</i> leads to higher starting doses and incremental dosage titration of extended-release tacro limus to achieve target trough concentrations. We suggest a higher starting dose of 0.2 mg/kg/d for <i>CYP3A5</i> expressers.</p>","PeriodicalId":65557,"journal":{"name":"世界移植杂志","volume":"13 6","pages":"368-378"},"PeriodicalIF":0.0,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10758687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}