A5035935257- Renal Transplantation Outcomes and Treatments
- Pharmacological Effects and Toxicity Studies
- Renal and Vascular Pathologies
- Pharmacogenetics and Drug Metabolism
- Organ Transplantation Techniques and Outcomes
- Chronic Kidney Disease and Diabetes
- Drug Transport and Resistance Mechanisms
- Acute Kidney Injury Research
- Neurological Complications and Syndromes
- Organ Donation and Transplantation
- Renal Diseases and Glomerulopathies
- Drug-Induced Hepatotoxicity and Protection
- T-cell and B-cell Immunology
- Global Health Care Issues
- Liver Disease and Transplantation
- Immune Response and Inflammation
- Healthcare Policy and Management
- Metabolism and Genetic Disorders
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Pediatric Urology and Nephrology Studies
- Dialysis and Renal Disease Management
- Renal function and acid-base balance
- Stress Responses and Cortisol
- Muscle and Compartmental Disorders
- Healthcare cost, quality, practices
AstraZeneca (United Kingdom)
2020-2024
St George's, University of London
2012-2022
St George’s University Hospitals NHS Foundation Trust
2011-2021
AstraZeneca (Sweden)
2021
St George's Hospital
2000-2020
St George's Hospital
2000-2019
University of London
2012-2015
Renal Association
2015
South West London and St George's Mental Health NHS Trust
2013
Roche (Switzerland)
2007
Lewis rats with experimental allergic encephalomyelitis (EAE), induced either by the subcutaneous injection of guinea pig myelin basic protein (MBP) or adoptive transfer MBP-primed spleen cells, suffer from a single episode paralysis which they recover spontaneously. Animals developing EAE were found to have greatly elevated levels corticosterone in blood. This endogenous increase steroid production was accompanied lymphopenia and depressed delayed-type hypersensitivity responses OVA,...
Background. There is marked heterogeneity in blood concentrations of tacrolimus following standard body-weight-based dosing. This most apparent black patients, who have a higher dose requirement when compared with other ethnic groups. Differences intestinal P-glycoprotein and hepatic cytochrome P4503A activity been postulated as contributing to this problem. Methods. The dose-normalized at 3 months after renal transplantation were related CYP3AP1 multiple drug resistance (MDR)-1 genotypes...
Previously, we reported that, at 3 months after renal transplantation, individuals with CYP3AP1 genotype CYP3AP1*1 (linked to CYP3A5*1 and strongly associated expression of CYP3A5) required twofold higher doses tacrolimus achieve target blood concentrations than the CYP3AP1*3/*3 (CYP3A5 nonexpressors). This study assesses relationship between concentration-controlled dosing during early period time in 178 transplant recipients (CYP3AP1*1/*3 or *1/*1: n = 53, CYP3AP1*3/*3: 125). Patients...
Previously, we demonstrated that the dose-normalized tacrolimus blood concentration after renal transplantation was associated with a single nucleotide polymorphism (SNP) in CYP3AP1 gene, probably through linkage an SNP CYP3A5 gene. Individuals at least one CYP3A5*1 allele synthesize and CYP3A5*3/*3 homozygotes do not. We now present results direct typing of genotype for this group 180 kidney-only transplant recipients from center. South Asian white patients achieved twofold lower...
There is a dearth of data on end-stage renal disease (ESRD) in Africa. Several national registries have been established but not sustainable because resource limitations. The African Association Nephrology (AFRAN) and the Paediatric (AFPNA) recognize importance good registry plan to establish an Renal Registry. This article reviews elements needed for successful gives overview developed developing countries, with emphasis It then discusses proposed Registry first steps towards its...
We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression B cell–related genes relative expansions cell subsets. However, all these studies, index group—namely, tolerant recipients—were not receiving immunosuppression (IS) treatment, unlike rest comparator groups. aimed to assess confounding effect regimens develop a novel IS-independent signature tolerance. Analyzing gene three independent transplant patient cohorts (232...
This study examined the efficacy of C.E.R.A., a continuous erythropoietin receptor activator, for correcting anemia in patients who had chronic kidney disease (CKD) and were not on dialysis.In this open-label, randomized, parallel-group, Phase III study, 324 adult with CKD dialysis nor receiving treatment erythropoiesis-stimulating agents (ESAs) randomly assigned (1:1) to receive subcutaneous C.E.R.A. once every 2 wk or darbepoetin alfa weekly during an 18-wk correction period 10-wk...
Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate long-term failure. Mismatches between donor and recipient HLA play an important role the acute chronic allogeneic immune response against graft. Perfect matching at clinically relevant loci does obviate need for immunosuppression, suggesting that additional genetic variation plays a critical both short- graft outcomes. By combining patient data samples from supranational...
The aim of this study was to determine whether plasma concentrations the acyl (AcMPAG) and phenolic (MPAG) glucuronide metabolites mycophenolic acid (MPA) were related diarrhoea in renal transplant patients on mycophenolate mofetil (MMF) with cyclosporine (CsA) or tacrolimus (TCL). Blood samples (0, 30, 120 min) taken at days 3, 10, week 4, months 6 12 for determination MPA, MPAG AcMPAG. MPA-AUC estimated using validated algorithms. Two hour AUCs calculated Immunosuppressive therapy...
P-glycoprotein (P-gp) and the drug metabolizing enzymes have major pharmacokinetic effects. Variability in tacrolimus absorption is influenced by P-gp activity which, turn, affected single nucleotide polymorphisms (SNPs) within multidrug resistance-1 gene (MDR-1). Tacrolimus dose requirements of 206 stable renal transplant patients were related to MDR-1 genotypes SNPs C1236T, G2677T/A C3435T, as well haplotypes: C-G-C T-T-T. Lower dose-normalized blood concentrations achieved for: 2677-GG...
Experimentally induced and naturally occurring inflammatory diseases of the central nervous system (CNS) are often associated with a breakdown blood-brain barrier edema within CNS itself. CD4+ T cells now clearly implicated in pathogenesis disease, experimental autoimmune encephalomyelitis, previous vivo experiments had indicated that these may be capable directly damaging vasculature. To assess capacity to damage brain vascular endothelial (EC) vitro, two lines specificity for myelin basic...
Pharmacogenetics has the potential to complement therapeutic drug monitoring in achieving target blood concentrations of immunosuppressive drugs during critical early period after transplantation when adequate exposure is essential prevent rejection. The most attractive candidate for a pharmacogenetic strategy tacrolimus dosing based on CYP3A5 genotype.
An algorithm based on the CYP3A5 genotype to predict tacrolimus clearance inform optimal initial dose was derived using data from DeKAF study (Passey et al. Br J Clin Pharmacol 2011; 72: 948-57) but not tested in an independent cohort of patients. Our aim test whether dosing could estimated renal transplant recipients at our centre.
Background. Since the introduction of cyclosporine (CsA), 1-year renal allograft survival has improved, but concern persists about long-term adverse effects CsA, especially with respect to function and blood pressure. This randomized controlled trial was set up establish whether withdrawal CsA would alter outcome. Methods. Adult patients who, at 1 year after transplantation, had a stable serum creatinine less than 300 µmol/L who not acute rejection within last 6 months were eligible for...
Background: The association of CYP3A5, CYP3A4, and ABCB1 single nucleotide polymorphisms (SNPs) with cyclosporine (CsA) pharmacokinetics is controversial. authors studied the influence these SNPs on CsA as well incidence biopsy-proven acute rejection (BPAR) renal function after kidney transplantation. Method: One hundred seventy-one patients participating in an international, randomized controlled trial were genotyped for CYP3A5*3, CYP3A4*1B 1236 C>T, 2677 G>T/A, 3435 C>T SNPs. treated CsA,...
The risk of long-term chronic allograft nephropathy and graft loss after kidney transplantation is increased in patients with a high intrapatient variability the clearance tacrolimus. CYP3A5 genotype has significant influence on oral bioavailability tacrolimus potential exposure.The study population consisted 118 renal transplant recipients stable function 12 months transplant. concentration was calculated. were divided into low- high-intraindividual groups using median as cutoff value.No...
Introduction. RIFLE and AKIN provide a standardised classification of acute kidney injury (AKI), but their categorical rather than continuous nature restricts use to research tool. A more accurate real-time description renal function in AKI is needed, some published data suggest that equations based on serum creatinine estimate glomerular filtration rate (eGFR) can this. In addition, incorporating cystatin C concentration into estimates GFR may improve accuracy, no eGFR are validated...