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pharmacogenomics

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22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2020/10/30

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Pharmacogenomics and Cardiovascular Disease: Where are We and Where do We go from Here?

Arq Bras Cardiol. 2020 Oct;115(4):690-700

Authors: Stein R, Beuren T, Cela LR, Ferrari F

PMID: 33111871 [PubMed - in process]

Data on compounding lopinavir and ritonavir suspension for non-cooperative COVID-19 patients.

Data Brief. 2020 Oct 23;:106445

Authors: Zanon D, Musazzi UM, Manca A, De Nicolò A, D'Avolio A, Cilurzo F, Maximova N, Tomasello C, Clementi E, Minghetti P

Abstract
The COVID-19 outbreak is now one of the most critical crises to manage for most of the national healthcare systems in the world. The situation has been complicated by the absence of a vaccine and authorised pharmacological treatments, except for remdesivir. In this context, many medicaments, including different Ebola or HIV antivirals, are used off-label in the hospital wards as life-treating medicines for COVID-19 patients. Authorized medicaments manipulation is sometimes necessary because they are not always formulated to be administered to non-cooperative patients or they are in shortage. It is this the case of the fixed combination of lopinavir/ritonavir, which was extensively used in the first phase of the outbreak inducing a shortage of the oral solution available in the EU market as an oral liquid solution and. Unfortunately, the increased worldwide demand and the reduced goods movements are causing the shortage of the liquid solution. This work provides data on size distribution, osmolarity other than drug chemical stability of a lopinavir/ritonavir extemporaneous preparation prepared by using as drug source the solid dosage form (i.e., tablet) available on the market. The reported data indicate that such preparation is suitable to be delivered through a nasogastric tube, and enough stable for two weeks from the preparation at room temperature.

PMID: 33110933 [PubMed - as supplied by publisher]

Dissecting the mechanism of Yuzhi Zhixue granule on ovulatory dysfunctional uterine bleeding by network pharmacology and molecular docking.

Chin Med. 2020;15:113

Authors: Li J, Luo H, Liu X, Zhang J, Zhou W, Guo S, Chen X, Liu Y, Jia S, Wang H, Li B, Cheng G, Wu J

Abstract
Background: Yuzhi Zhixue Granule (YZG) is a traditional Chinese patent medicine for treating excessive menstrual flow caused by ovulatory dysfunctional uterine bleeding (ODUB) accompanied by heat syndrome. However, the underlying molecular mechanisms, potential targets, and active ingredients of this prescription are still unknown. Therefore, it is imperative to explore the molecular mechanism of YZG.
Methods: The active compounds in YZG were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The putative targets of YZG were collected via TCMSP and Search Tool for Interacting Chemicals (STITCH) databases. The Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGKB) databases were used to identify the therapeutic targets of ODUB. A protein-protein interaction (PPI) network containing both the putative targets of YZG and known therapeutic targets of ODUB was built. Furthermore, bioinformatics resources from the database for annotation, visualization and integrated discovery (DAVID) were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to verify the binding effect between the YZG screened compounds and potential therapeutic target molecules.
Results: The study employed a network pharmacology method, mainly containing target prediction, network construction, functional enrichment analysis, and molecular docking to systematically research the mechanisms of YZG in treating ODUB. The putative targets of YZG that treat ODUB mainly involved PTGS1, PTGS2, ALOX5, CASP3, LTA4H, F7 and F10. The functional enrichment analysis suggested that the produced therapeutic effect of YZG against ODUB is mediated by synergistical regulation of several biological pathways, including apoptosis arachidonic acid (AA) metabolism, serotonergic synapse, complement and coagulation cascades and C-type lectin receptor signaling pathways. Molecular docking simulation revealed good binding affinity of the seven putative targets with the corresponding compounds.
Conclusion: This novel and scientific network pharmacology-based study holistically elucidated the basic pharmacological effects and the underlying mechanisms of YZG in the treatment of ODUB.

PMID: 33110441 [PubMed]

Population impact of pharmacogenetic tests in admixed populations across the Americas.

Pharmacogenomics J. 2020 Oct 27;:

Authors: Suarez-Kurtz G

Abstract
The current population of the Americas (~1 billion people) is highly heterogeneous as a result of five centuries of admixture between three major parental populations, namely Native Amerindians, Europeans, and subSaharan Africans. This heterogeneity has important pharmacogenetic (PGx) implications. The present study explores this issue with respect to the population impact of PGx tests listed in the CPIC and DWPG guidelines for the cancer chemotherapeutic agents fluoropyrimidines, irinotecan, and thiopurines. Population impact was assessed by the number of individuals needed to genotype (NNG) and to treat [NNT] in order to prevent one additional adverse effect. The 1000 Genomes Project database was accessed to obtain genotypes for the relevant PGx markers and to estimate individual proportions of Native, European, and African ancestry for six recently admixed populations across the Americas. The ancestry proportions were then employed to devise three sub-cohorts, denoted NAT, EUR, and AFR, in which one of the three major ancestral roots predominates largely (8 to 30-fold) over the other two. Minor allele frequency (MAF) of NUDT15 rs116855232, TPMT rs1800460, and UGT1A1 rs887829 differed significantly across the three sub-cohorts, whereas no difference was observed for TPMT rs1142345 and 1800462, and the four DPYD variants interrogated. The frequency of combined TPMT/NUDT and UGT1A1, but not DPD, metabolic phenotypes differed significantly among the sub-cohorts. The NNGs for the drug/sub-cohorts pairs, ranged from 12 (irinotecan/UGT1A1 in EUR) to 360 (fluoropyrimidines/DPYD in NAT). Differences in MAF of the interrogated variants and consequently in the distribution of metabolic phenotypes, plus the variable individual proportions of biogeographical ancestry concur to the 30-fold range of NNGs for the PGx tests, across the sub-cohorts. This large variation is likely to influence the perceived benefits and the clinical adoption of PGx screening for the chemotherapeutic agents investigated. This is of especial concern for fluoropyrimidines, in view of the large NNGs observed in the study sub-cohorts (NNG = 176-360) and confirmed in cancer patients from Brazil (NNG = 312).

PMID: 33110249 [PubMed - as supplied by publisher]

Telomere length and genetic variant associations with interstitial lung disease progression and survival.

Eur Respir J. 2019 04;53(4):

Authors: Newton CA, Oldham JM, Ley B, Anand V, Adegunsoye A, Liu G, Batra K, Torrealba J, Kozlitina J, Glazer C, Strek ME, Wolters PJ, Noth I, Garcia CK

Abstract
Leukocyte telomere length (LTL), MUC5B rs35705950 and TOLLIP rs5743890 have been associated with idiopathic pulmonary fibrosis (IPF).In this observational cohort study, we assessed the associations between these genomic markers and outcomes of survival and rate of disease progression in patients with interstitial pneumonia with autoimmune features (IPAF, n=250) and connective tissue disease-associated interstitial lung disease (CTD-ILD, n=248). IPF (n=499) was used as a comparator.The LTL of IPAF and CTD-ILD patients (mean age-adjusted log-transformed T/S of -0.05±0.29 and -0.04±0.25, respectively) is longer than that of IPF patients (-0.17±0.32). For IPAF patients, LTL <10th percentile is associated with faster lung function decline compared to LTL ≥10th percentile (-6.43% per year versus -0.86% per year; p<0.0001) and worse transplant-free survival (hazard ratio 2.97, 95% CI 1.70-5.20; p=0.00014). The MUC5B rs35705950 minor allele frequency (MAF) is greater for IPAF patients (23.2, 95% CI 18.8-28.2; p<0.0001) than controls and is associated with worse transplant-free IPAF survival (hazard ratio 1.92, 95% CI 1.18-3.13; p=0.0091). Rheumatoid arthritis (RA)-associated ILD (RA-ILD) has a shorter LTL than non-RA CTD-ILD (-0.14±0.27 versus -0.01±0.23; p=0.00055) and higher MUC5B MAF (34.6, 95% CI 24.4-46.3 versus 14.1, 95% CI 9.8-20.0; p=0.00025). Neither LTL nor MUC5B are associated with transplant-free CTD-ILD survival.LTL and MUC5B MAF have different associations with lung function progression and survival for IPAF and CTD-ILD.

PMID: 30635297 [PubMed - indexed for MEDLINE]

Correction to "Carboxylesterase 1 and Precision Pharmacotherapy: Pharmacogenetics and Nongenetic Regulators".

Drug Metab Dispos. 2020 Nov;48(11):1246

Authors:

PMID: 33106252 [PubMed]

Therapeutic drug monitoring of mycophenolate mofetil in pediatric patients: novel techniques and current opinion.

Expert Opin Drug Metab Toxicol. 2020 Oct 27;:

Authors: Ehren R, Schijvens AM, Hackl A, Schreuder MF, Weber LT

Abstract
INTRODUCTION: Mycophenolate mofetil (MMF) is an ester prodrug of the immunosuppressant mycophenolic acid (MPA) and is recommended and widely used for maintenance immunosuppressive therapy in solid organ and stem-cell transplantation as well as in immunological kidney diseases. MPA is a potent, reversible, non-competitive inhibitor of the inosine monophosphate dehydrogenase (IMPDH), a crucial enzyme in the de novo purine synthesis in T- and B-lymphocytes, thereby inhibiting cell-mediated immunity and antibody formation. The use of therapeutic drug monitoring (TDM) of MMF is still controversial as outcome data of clinical trials are equivocal.
AREAS COVERED: This review covers in great depth the existing literature on TDM of MMF in the field of pediatric (kidney) transplantation. In addition, the relevance of TDM in immunological kidney diseases, in particular childhood nephrotic syndrome is highlighted.
EXPERT OPINION: TDM of MMF has the potential to optimize therapy in pediatric transplantation as well as in nephrotic syndrome. Limited sampling strategies to estimate MPA exposure increase its feasibility. Future perspectives rather encompass approaches reflecting total immunosuppressive load than single drug TDM.

PMID: 33107768 [PubMed - as supplied by publisher]

Low Tenofovir Plasma Exposure in HIV Oral Pre-exposure Prophylaxis Recipients with Gastrointestinal Disorders.

Antimicrob Agents Chemother. 2020 Oct 26;:

Authors: Calcagno A, Dal Conte I, Cattaneo D, Testi R, Mistrangelo M, Gervasoni C, de Nicolò A, Bonora S, D'Avolio A, Di Perri G

Abstract
Four pre-exposure prophylaxis (PrEP) users with gastro-intestinal disorders (sleeve gastrectomy, terminal ileitis, celiac disease or chronic diarrhea) and receiving oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) were included. Despite a self-reported high adherence, trough plasma tenofovir concentrations (after a supervised intake) were significantly lower than those observed in PrEP recipients without gastrointestinal disorders [21 (±9.1) vs. 138 (±85) ng/mL]. PrEP users with gastrointestinal disorders may need increased TDF doses or alternative prophylactic measures.

PMID: 33106270 [PubMed - as supplied by publisher]

Treatment and resistance mechanisms in castration-resistant prostate cancer: new implications for clinical decision making?

Expert Rev Anticancer Ther. 2020 Oct 27;:

Authors: Norz V, Rausch S

Abstract
INTRODUCTION: The armamentarium of treatment options in metastatic and non-metastatic CRPC is rapidly evolving. However, the question of how individual treatment decisions should be balanced by available predictive clinical parameters, pharmacogenetic and drug interaction profiles, or compound-associated molecular biomarkers is a major challenge for clinical practice.
AREAS COVERED: We discuss treatment and resistance mechanisms in PC with regard to their association to drug efficacy and tolerability. Current efforts of combination treatment and putative predictive biomarkers of available and upcoming compounds are highlighted with regard to their implication on clinical decision making.
EXPERT OPINION: Several treatment approaches are delineated, where identification of resistance mechanisms in CRPC may guide treatment selection. To date, most of these candidate biomarkers will however be found only in a small subset of patients. While current approaches of combination treatment in CRPC are proving synergistic effects on cancer biology, higher complexity with regard to biomarker analysis and interaction profiles of the respective compounds may be expected. Among other aspects of personalized treatment, consideration of drug-drug interaction and pharmacogenetics is an underrepresented issue. However, the non-metastatic castration prostate cancer situation may be an example for selection based on drug interaction profiles in the future.

PMID: 33106066 [PubMed - as supplied by publisher]

Telemedicine and adherence monitoring in children with asthma.

Curr Opin Pulm Med. 2020 Oct 21;:

Authors: Blake KV

Abstract
PURPOSE OF REVIEW: Telemedicine, defined as synchronous video visits between a provider and a child with asthma, often takes place in the school setting. This review examines the new electronic sensors for adherence monitoring and studies that used telemedicine in the school setting to improve asthma outcomes.
RECENT FINDINGS: School-based telemedicine provides an important service to families of school-aged children who have difficulty due to time and distance in planning and keeping in-person appointments with primary or specialty providers. Significant improvements in objective measures of asthma control are inconsistently observed although caregiver and parent quality of life and child self-management behaviors are improved and satisfaction is high. Assessment and outcomes related to adherence are mentioned in studies but results are not often reported. However, it appears that adherence interventions are beneficial while maintained but the effects are not sustained upon intervention discontinuation.
SUMMARY: The school setting provides a convenient and suitable environment to conduct telemedicine visits between school-aged children and their primary care or specialty provider. Electronic adherence sensors allow review of controller and rescue medication use through a cloud-based dashboard and provides an opportunity for real-time assessment and intervention by providers to improve asthma outcomes.

PMID: 33105234 [PubMed - as supplied by publisher]

Pharmacogenetic profiling of dihydropyrimidine dehydrogenase (DPYD) variants in the Indian population.

J Gene Med. 2020 Oct 26;:e3289

Authors: Naushad SM, Hussain T, Alrokayan S, Kutala VK

Abstract
BACKGROUND: To delineate the pharmacologically relevant dihydropyrimidine dehydrogenase (DPYD) variants in the Indian population.
METHODS: We have screened 2000 Indian subjects for DPYD variants using Infinium Global Screening Array (GSA).
RESULTS: The GSA analysis has identified seven coding, two intronic, and three synonymous DPYD variants. Level 1A alleles (rs75017182, rs3918290, P633Qfs*5, D949V) were found to be rare (minor allele frequency: 1.889%), while Level 3 alleles were observed to be predominant (C29R: 24.91%, I543V: 9.047%, M166V: 8.993%, V732I: 8.44%). In silico predictions have revealed that all Level 1A alleles were deleterious, while three (M166V, S534N, V732I) of seven Level 3 alleles were damaging. CUPSAT analysis has revealed that two Level 1A (P633Qfs*, D949V) and three Level 3 (I543V, V732I, S534N) variants were thermolabile. Pooled Indian data has showed that V732I, S534N, and rs3918290 variants are associated with 5-FU/Capecitabine toxicity, while C29R, I543V, and M166V variants exhibited the null association. A comparison of our data with the other population data from the "Allele Frequency Aggregator" database showed similarities with the South Asian data.
CONCLUSIONS: We have identified four Level 1A (non-functional/dysfunctional) and the seven Level 3 variants in the DPYD gene. Pooled Indian data has revealed the association of V732I, S534N, and rs3918290 variants with 5-FU/Capecitabine toxicity. Clustering analysis has shown the similarities in the DPYD profiles of the Indian and South Asian populations.

PMID: 33105068 [PubMed - as supplied by publisher]

A review of novel biomarkers and imaging techniques for assessing the severity of chemotherapy-induced peripheral neuropathy.

Expert Opin Drug Metab Toxicol. 2020 Oct 26;:

Authors: Alberti P

Abstract
INTRODUCTION: Chemotherapy induced peripheral neuropathy (CIPN) is a potentially persistent late toxicity of most common anticancer regimens. There is still a huge lack in CIPN assessment in clinical trials, therefore, biomarkers, both neuroimagery and molecular, could fill this gap.
AREAS COVERED: In this review the first applications of high-resolution ultrasound (HRUS), magnetic resonance imaging (MRI) are discussed; different molecular biomarkers first reports in CIPN are also addressed, broadening the spectrum of potential molecular candidates beyond pharmacogenomics.
EXPERT OPINION: At the present moment, neuroimaging and biomarkers are not yet part of the clinical practice for CIPN management, but they deserved to be tested since they could be a valuable surrogate endpoint in clinical trial. To ascertain the appropriateness of (a) potential biomarker(s), it is crucial to design a clinical trial based on sound design and taking advantage of international, multidisciplinary initiatives, such as the Toxic Neuropathy Consortium.

PMID: 33103947 [PubMed - as supplied by publisher]

Exploratory meta-analysis on dose-related efficacy and complications of rhBMP-2 in anterior cervical discectomy and fusion: 1,539,021 cases from 2003 to 2017 studies.

J Orthop Translat. 2020 Sep;24:166-174

Authors: Wen YD, Jiang WM, Yang HL, Shi JH

Abstract
Background/Objective: Anterior cervical discectomy and fusion (ACDF), commonly using autogenous iliac bone graft may be limited by donor site availability, donor-site morbidity, lower fusion rate among specific patients and longer surgical time. Surgeons used rhBMP-2 as an alternative in order to fill these clinical needs. However, studies comparing with and without rhBMP-2 in ACDF have reported conflicting results on efficacy and complications. Therefore, the purpose of this article was to evaluate efficacy and complications through dose-related rhBMP-2 and surgical level-dependence in ACDF.
Methods: We comprehensively searched PubMed and the Cochrane Library and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs), prospective and retrospective comparative studies assessing with and without rhBMP-2 treatments.
Results: 1 RCTs, 4 prospective studies and 24 retrospective studies including a total of 1,539,021 cases were identified. Patients in ACDF with rhBMP-2 might benefit from significantly higher fusion rates than that in non-rhBMP-2, not only total value but also in 3 tiers of rhBMP-2 doses. It is worth noting that the low dose of rhBMP-2 (<0.7 mg/level) showed highest fusion rate among all rhBMP-2 doses. Patients in rhBMP-2 also experienced higher complication rate, dysphagia and wound infections than that in non-rhBMP-2. In 2-level ACDF, the fusion rate was significantly better in rhBMP-2 than non-rhBMP-2 but not for complication rate. Surgery operative time, lengths of hospital stay and neurologic symptoms did not differ significantly between two treatments.
Conclusions: rhBMP-2 chosen in ACDF offered higher fusion, but also higher complication rate with more dysphagia and wound infections than non-rhBMP-2. To gain the efficacy and safety, rhBMP-2 dosing recommendations for ACDF would be better < 0.7 mg/level. Moreover, rhBMP-2 may be an option to improve nonunion in high risk of multi-level ACDF.
The translational potential of this article: This article indicated that the product development of facilities used in ACDF, the dose of rhBMP-2 may be lower than 0.7 mg/level was enough to gain the good fusion rates. However, the complications were higher in patients used rhBMP-2, therefore the manufacturers should pay attention to mitigate such side effects.

PMID: 33101967 [PubMed]

Clinical Relevance of Pharmacogenetics in Serotonin Syndrome.

Case Rep Psychiatry. 2020;2020:8860434

Authors: Pandya D, Tran M, Verduzco-Gutierrez M

Abstract
Serotonin syndrome is a predictable life-threatening condition that is caused by serotonergic stimulation of the central and peripheral nervous systems. A patient's genetic profile can amplify exposure risk as many serotonergic drugs are metabolized by CYP450 enzymes, and these enzymes may be altered in functionality. We report a case of an elderly man who presented with serotonin syndrome after a dose change in valproic acid 5 weeks prior. His medication list consisted of low-dose serotonergic agents, which is unusual as most cases of serotonin syndrome involve higher doses. A review of his pharmacogenetic profile is presented to retrospectively evaluate the additive risk for serotonin syndrome and implications on resuming serotonergic agents.

PMID: 33101751 [PubMed]

The Pharmacogenomics Journal: there is a new chief in town.

Pharmacogenomics J. 2020 Oct 26;:

Authors: Patrinos GP

PMID: 33100321 [PubMed - as supplied by publisher]

Dicoumarol suppresses HMGA2-mediated oncogenic capacities and inhibits cell proliferation by inducing apoptosis in colon cancer.

Biochem Biophys Res Commun. 2020 04 16;524(4):1003-1009

Authors: Chen CH, Hsieh YC, Yang PM, Liu YR, Cho EC

Abstract
Colon cancer is one of the leading causes of cancer-related deaths and its five-year survival rate remains low in locally advanced or metastatic stages of colon cancer. Overexpression of high mobility group protein AT-hook2 (HMGA2) is associated with cancer progression, metastasis, and poor prognosis in many malignancies. Oxidative stress regulates cellular mechanisms and provides an environment that favors the cancer cells to survive and progress, yet, at the same time, oxidative stress can also be utilized as a cancer-damaging strategy. The molecular regulatory roles of HMGA2 in oxidative stress and their involvement in cancer progression are largely unknown. In this study, we investigated the involvement of HMGA2 in regulation of oxidative stress responses by luciferase reporter assays. Moreover, we utilized dicoumarol (DIC), a derivative of coumarin which has been suggested to be involved in oxidation regulation with anticancer effects, and demonstrated that DIC could induce apoptosis and inhibit cell migration of HMGA2 overexpressing colon cancer cells. Further investigation also evidenced that DIC can enhance the cancer inhibition effect of 5-FU in colony formation assays. Taken together, our data revealed novel insights into the molecular mechanisms underlying HMGA2 and highlighted the possibility of targeting the cellular antioxidant system for treating patients and preventing from cancer progression in HMGA2 overexpressing colon cancer cells.

PMID: 32063361 [PubMed - indexed for MEDLINE]

Profiling the Non-genetic Origins of Cancer Drug Resistance with a Single-Cell Functional Genomics Approach Using Predictive Cell Dynamics.

Cell Syst. 2020 Oct 21;11(4):367-374.e5

Authors: Meyer M, Paquet A, Arguel MJ, Peyre L, Gomes-Pereira LC, Lebrigand K, Mograbi B, Brest P, Waldmann R, Barbry P, Hofman P, Roux J

Abstract
Non-genetic heterogeneity observed in clonal cell populations is an immediate cause of drug resistance that remains challenging to profile because of its transient nature. Here, we coupled three single-cell technologies to link the predicted drug response of a cell to its own genome-wide transcriptomic profile. As a proof of principle, we analyzed the response to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) in HeLa cells to demonstrate that cell dynamics can discriminate the transient transcriptional states at the origin of cell decisions such as sensitivity and resistance. Our same-cell approach, named fate-seq, can reveal the molecular factors regulating the efficacy of a drug in clonal cells, providing therapeutic targets of non-genetic drug resistance otherwise confounded in gene expression noise. A record of this paper's transparent peer review process is included in the Supplemental Information.

PMID: 33099406 [PubMed - in process]

The tacrolimus metabolism affect post-transplant outcome mediating acute rejection and delayed graft function: analysis from Korean Organ Transplantation Registry (KOTRY) data.

Transpl Int. 2020 Oct 24;:

Authors: Ro H, Jeong JC, Kong JM, Min JW, Park SK, Lee J, Koo TY, Yang J, Kim MS, Hwang S, Ahn C

Abstract
BACKGROUND: Tacrolimus is a key drug in kidney transplantation (KT) with a narrow therapeutic index. The association between the tacrolimus metabolism rate and KT outcomes have not been investigated in large-scale multi-center studies.
METHODS: The Korean Organ Transplantation Registry (KOTRY) datasets were used. A total of 3,456 KT recipients were analyzed. The tacrolimus metabolism rate was defined as blood trough concentration of tacrolimus (C0 ) divided by the daily dose (D).
RESULTS: The patients were grouped into fast, intermediate, or slow metabolizers by the C0 /D measured 6 months after transplantation. The slow metabolism group was associated with a 2.7 ml/min/1.73 m2 higher adjusted estimated glomerular filtration rate (eGFR) at 6 months (95% confidence interval (C.I.) 1.2-4.3, p=0.001), less acute rejection (AR) within 6 months (Odds ratio (OR) 0.744, 95% C.I. 0.585-0.947, p=0.016), and less interstitial fibrosis and tubular atrophy (OR 0.606, 95% C.I. 0.390-0.940, p=0.025). Fast tacrolimus metabolism affected the 6-month post-KT eGFR through mediation of AR (natural indirect effect (NIE) -0.434, 95% C.I. -0.856--0.012, p=0.044) and delayed graft function (DGF) (NIE -0.119, 95% C.I. -0.231--0.007, p=0.038).
CONCLUSIONS: Slow tacrolimus metabolism was associated with better post-KT eGFR. AR and DGF were found to be significant mediators.

PMID: 33098694 [PubMed - as supplied by publisher]