J Zegarska1, E Hryniewiecka2, D Zochowska1, E Samborowska3, R Jazwiec3, A Borowiec3, W Tszyrsznic3, A Chmura4, S Nazarewski5, M Dadlez6, L Paczek7. 1. Transplantation Institute, Department of Immunology, Transplant Medicine, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland. 2. Department of Clinical Nursing, Medical University of Warsaw, Warsaw, Poland. 3. Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, Poland. 4. Transplantation Institute, Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland. 5. Department of General, Vascular, and Transplant Surgery, Medical University of Warsaw, Warsaw, Poland. 6. Institute of Biochemistry and Biophysics Polish Academy of Sciences, Warsaw, Poland; Department of Biology, University of Warsaw, Warsaw, Poland. 7. Transplantation Institute, Department of Immunology, Transplant Medicine, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland. Electronic address: leszek.paczek@wum.edu.pl.
Abstract
BACKGROUND: Tacrolimus (Tac) is one of the most commonly used immunosuppressive drugs after solid organ transplantation. Eight Tac metabolites have been described, but their clinical importance remains unclear. The aim of this study was quantification of the 2 major Tac metabolites, 13-O-demethyl (M-I) and 15-O-demethyl (M-III), in kidney transplant recipients and to link them with parameters of kidney and liver function, peripheral blood cell counts, and infection incidence. METHODS: In 81 kidney transplant recipients, concentrations of Tac, M-I, and M-III were measured with the use of liquid chromatography combined with tandem mass spectrometry (LC-MS-MS). RESULTS: There was a negative correlation between M-III levels and estimated glomerular filtration rate (eGFR; r = -0.244; P < .05). Also, a negative correlation between M-III concentrations and red blood cell count (RBC) was found (r = -0.349; P < .05). Neither concentrations of Tac nor of M-I correlated with eGFR or RBC. M-I, M-III, and Tac were not related to alanine aminotransferase activity. Significantly higher Tac and M-III concentrations in the group with all types of infections in comparison with the group without infections were observed (6.95 ± 2.09 ng/mL vs 5.73 ± 2.43 ng/mL [P = .03] and 0.27 ± 0.17 ng/mL vs 0.20 ± 0.11 ng/mL [P = .04], respectively). CONCLUSIONS: The results suggest that higher concentrations of M-III may have a nephrotoxic or myelotoxic effect and result in higher incidence of infections. Further studies are needed to confirm if monitoring of M-III could minimalize adverse effects such as nephrotoxicity or infections.
BACKGROUND:Tacrolimus (Tac) is one of the most commonly used immunosuppressive drugs after solid organ transplantation. Eight Tac metabolites have been described, but their clinical importance remains unclear. The aim of this study was quantification of the 2 major Tac metabolites, 13-O-demethyl (M-I) and 15-O-demethyl (M-III), in kidney transplant recipients and to link them with parameters of kidney and liver function, peripheral blood cell counts, and infection incidence. METHODS: In 81 kidney transplant recipients, concentrations of Tac, M-I, and M-III were measured with the use of liquid chromatography combined with tandem mass spectrometry (LC-MS-MS). RESULTS: There was a negative correlation between M-III levels and estimated glomerular filtration rate (eGFR; r = -0.244; P < .05). Also, a negative correlation between M-III concentrations and red blood cell count (RBC) was found (r = -0.349; P < .05). Neither concentrations of Tac nor of M-I correlated with eGFR or RBC. M-I, M-III, and Tac were not related to alanine aminotransferase activity. Significantly higher Tac and M-III concentrations in the group with all types of infections in comparison with the group without infections were observed (6.95 ± 2.09 ng/mL vs 5.73 ± 2.43 ng/mL [P = .03] and 0.27 ± 0.17 ng/mL vs 0.20 ± 0.11 ng/mL [P = .04], respectively). CONCLUSIONS: The results suggest that higher concentrations of M-III may have a nephrotoxic or myelotoxic effect and result in higher incidence of infections. Further studies are needed to confirm if monitoring of M-III could minimalize adverse effects such as nephrotoxicity or infections.
Authors: Nicholas A Kolaitis; Daniel R Calabrese; Patrick Ahearn; Aida Venado; Rebecca Florez; Huey-Ling Lei; Karolina Isaak; Erik Henricksen; Emily Martinez; Tiffany Chong; Rupal J Shah; Lorriana E Leard; Mary Ellen Kleinhenz; Jeffrey Golden; Teresa De Marco; John R Greenland; Jasleen Kukreja; Steven R Hays; Paul D Blanc; Jonathan P Singer Journal: Am J Health Syst Pharm Date: 2019-12-02 Impact factor: 2.637