Publications by authors named "My H S Svensson"

3 Publications

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Increased systemic exposure of once-daily tacrolimus in renal transplant recipients on marine omega-3 fatty acid supplementation.

Transpl Int 2021 May 15. Epub 2021 May 15.

Division of Medicine, Department of Renal Medicine, Akershus University Hospital, Lørenskog, Norway.

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http://dx.doi.org/10.1111/tri.13917DOI Listing
May 2021

Relative and absolute cancer risks among Nordic kidney transplant recipients-a population-based study.

Transpl Int 2020 12 25;33(12):1700-1710. Epub 2020 Sep 25.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post-transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval [CI]: 3.2-3.4). The AER of any cancer was 1560 cases (95% CI: 1468-1656) per 100 000 person-years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778-901), non-Hodgkin lymphoma (145, 95% CI: 119-174), lung cancer (126, 95% CI: 98.2-149), and kidney cancer (122, 95% CI: 98.0-149). The five- and ten-year cumulative incidence of any cancer was 8.1% (95% CI: 7.6-8.6%) and 16.8% (95% CI: 16.0-17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post-transplantation cancer vigilance.
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http://dx.doi.org/10.1111/tri.13734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756726PMC
December 2020

Determination of Tacrolimus Concentration and Protein Expression of P-Glycoprotein in Single Human Renal Core Biopsies.

Ther Drug Monit 2018 06;40(3):292-300

Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo.

Background: Tacrolimus (TAC) is currently the cornerstone of immunosuppressive protocols for renal transplant recipients. Despite therapeutic whole blood monitoring, TAC is associated with nephrotoxicity, and it has been hypothesized that intrarenal accumulation of TAC and/or its metabolites are involved. As TAC is a substrate of P-glycoprotein (P-gp), the expression and activity of this efflux transporter could influence the levels of TAC in renal tissue. The primary aim of this study was to develop and validate a method for quantification of TAC in tissue homogenates from single human renal core biopsies. The secondary aim was to provide measures of P-gp expression and of the demethylated metabolites of TAC in the same renal biopsy.

Methods: Human renal tissue, with and without clinical TAC exposure, was used for method development and validation. Homogenates were prepared with bead-beating, and concentrations of TAC and its demethylated metabolites were analyzed with liquid chromatography tandem mass spectrometry after protein precipitation. A Western blot method was used for semiquantification of P-gp expression in the homogenates. The final methods were applied to renal core biopsies from 2 transplant patients.

Results: The TAC assay showed within- and between-run mean accuracy between 99.7% and 107% and coefficients of variation ≤6.7%. Matrix effects were nonsignificant, and samples were stable for 3 months preanalytically when stored at -80°C. TAC concentrations in the renal core biopsies were 62.6 and 43.7 pg/mg tissue. The methods for measurement of desmethyl-TAC and P-gp expression were suitable for semiquantification in homogenates from renal core biopsies.

Conclusions: These methods may be valuable for the elucidation of the pharmacokinetic mechanisms behind TAC-induced nephrotoxicity in renal transplant recipients.
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http://dx.doi.org/10.1097/FTD.0000000000000510DOI Listing
June 2018