Marion Chapal1, Mélanie Néel, Florent Le Borgne, Emanuelle Meffray, Odette Carceles, Maryvonne Hourmant, Magalie Giral, Yohann Foucher, Anne Moreau, Fadi Fakhouri. 1. 1 ITUN, Department of Nephrology and Immunology, INSERM UMR S-1064, Nantes, France. 2 SPHERE (Biostatistics, Pharmacoepidemiology and Human Sciences Research) Laboratory-EA 4275, LabEx Transplantex, Nantes University, Nantes, France. 3 Department of Pathology, CHU de Nantes, Nantes, France. 4 Address correspondence to: Fadi Fakhouri, M.D., Ph.D., INSERM U643, ITUN, Université de Nantes and Nephrology Department CHU de Nantes, Nantes, France.
Abstract
BACKGROUND: Ischemia-reperfusion induces tubular and endothelial damage in the renal graft and leads to delayed graft function (DGF) and to an early loss of peritubular capillaries (PTC). Few, if any, clinical studies have assessed the impact of proangiogenic and antiangiogenic factors on endothelial repair during renal transplantation (RT)-related ischemia-reperfusion. METHODS: We prospectively assessed the kinetics of the antiangiogenic factor soluble Fms-like tyrosine kinase-1 (sFlt-1) in 136 consecutive RT patients and analyzed sFlt-1 impact on DGF and PTC loss. RESULTS: sFlt-1 plasma levels increased by twofold to threefold throughout the first week after RT. This increase was more marked in recipients of grafts from deceased donors compared with living donors. Patients with DGF had higher sFlt-1 levels at all time points during the first 7 days after RT and a higher peak sFlt-1 compared with those without DGF. In multivariate analysis, a peak plasma sFlt-1 of 250 pg/mL or higher was associated with 2.5-fold increase in the risk of DGF (P=0.04). Similarly, patients with a peak plasma sFlt-1 of 250 pg/mL or higher had a more pronounced early decrease in PTC compared with those with a peak sFlt-1 less than 250 pg/mL. CONCLUSIONS: sFlt-1 is a new nonimmunologic independent risk factor for DGF and PTC loss. Its inhibition may help improve the outcome of RT.
BACKGROUND:Ischemia-reperfusion induces tubular and endothelial damage in the renal graft and leads to delayed graft function (DGF) and to an early loss of peritubular capillaries (PTC). Few, if any, clinical studies have assessed the impact of proangiogenic and antiangiogenic factors on endothelial repair during renal transplantation (RT)-related ischemia-reperfusion. METHODS: We prospectively assessed the kinetics of the antiangiogenic factor soluble Fms-like tyrosine kinase-1 (sFlt-1) in 136 consecutive RT patients and analyzed sFlt-1 impact on DGF and PTC loss. RESULTS: sFlt-1 plasma levels increased by twofold to threefold throughout the first week after RT. This increase was more marked in recipients of grafts from deceased donors compared with living donors. Patients with DGF had higher sFlt-1 levels at all time points during the first 7 days after RT and a higher peak sFlt-1 compared with those without DGF. In multivariate analysis, a peak plasma sFlt-1 of 250 pg/mL or higher was associated with 2.5-fold increase in the risk of DGF (P=0.04). Similarly, patients with a peak plasma sFlt-1 of 250 pg/mL or higher had a more pronounced early decrease in PTC compared with those with a peak sFlt-1 less than 250 pg/mL. CONCLUSIONS: sFlt-1 is a new nonimmunologic independent risk factor for DGF and PTC loss. Its inhibition may help improve the outcome of RT.
Authors: Faikah Gueler; Nelli Shushakova; Michael Mengel; Katja Hueper; Rongjun Chen; Xiaokun Liu; Joon-Keun Park; Hermann Haller; Gert Wensvoort; Song Rong Journal: PLoS One Date: 2015-01-24 Impact factor: 3.240
Authors: Cleo C L van Aanhold; Angela Koudijs; Kyra L Dijkstra; Ron Wolterbeek; Jan A Bruijn; Cees van Kooten; Hans J Baelde Journal: Int J Mol Sci Date: 2022-08-26 Impact factor: 6.208
Authors: Theresa M Wewers; Annika Schulz; Ingo Nolte; Hermann Pavenstädt; Marcus Brand; Giovana S Di Marco Journal: J Am Soc Nephrol Date: 2021-06-21 Impact factor: 14.978