Elisabet Van Loon1,2, Aleksandar Senev1,3, Evelyne Lerut4,5, Maarten Coemans1,6, Jasper Callemeyn1,2, Jan M Van Keer1, Liesbeth Daniëls3, Dirk Kuypers1,2, Ben Sprangers2,7, Marie-Paule Emonds1,3, Maarten Naesens1,2. 1. Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium. 2. Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium. 3. Histocompatibility and Immunogenetic Laboratory, Red Cross-Flanders, Mechelen, Belgium. 4. Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. 5. Department of Pathology, University Hospitals Leuven, Leuven, Belgium. 6. Leuven Biostatistics and Statistical Bioinformatics Centre, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. 7. Department of Microbiology and Immunology, Laboratory of Molecular Immunology, Rega Institute, KU Leuven, Leuven, Belgium.
Abstract
BACKGROUND: Although graft loss is a primary endpoint in many studies in kidney transplantation and a broad spectrum of risk factors has been identified, the eventual causes of graft failure in individual cases remain ill studied. METHODS: We performed a single-center cohort study in 1000 renal allograft recipients, transplanted between March 2004 and February 2013. RESULTS: In total, 365 graft losses (36.5%) were identified, of which 211 (57.8%) were due to recipient death with a functioning graft and 154 (42.2%) to graft failure defined as return to dialysis or retransplantation. The main causes of recipient death were malignancy, infections, and cardiovascular disease. The main causes of graft failure were distinct for early failures, where structural issues and primary nonfunction prevailed, compared to later failures with a shift towards chronic injury. In contrast to the main focus of current research efforts, pure alloimmune causes accounted for only 17.5% of graft failures and only 7.4% of overall graft losses, although 72.7% of cases with chronic injury as presumed reason for graft failure had prior rejection episodes, potentially suggesting that alloimmune phenomena contributed to the chronic injury. CONCLUSIONS: In conclusion, this study provides better insight in the eventual causes of graft failure, and their relative contribution, highlighting the weight of nonimmune causes. Future efforts aimed to improve outcome after kidney transplantation should align with the relative weight and expected impact of targeting these causes.
BACKGROUND: Although graft loss is a primary endpoint in many studies in kidney transplantation and a broad spectrum of risk factors has been identified, the eventual causes of graft failure in individual cases remain ill studied. METHODS: We performed a single-center cohort study in 1000 renal allograft recipients, transplanted between March 2004 and February 2013. RESULTS: In total, 365 graft losses (36.5%) were identified, of which 211 (57.8%) were due to recipient death with a functioning graft and 154 (42.2%) to graft failure defined as return to dialysis or retransplantation. The main causes of recipient death were malignancy, infections, and cardiovascular disease. The main causes of graft failure were distinct for early failures, where structural issues and primary nonfunction prevailed, compared to later failures with a shift towards chronic injury. In contrast to the main focus of current research efforts, pure alloimmune causes accounted for only 17.5% of graft failures and only 7.4% of overall graft losses, although 72.7% of cases with chronic injury as presumed reason for graft failure had prior rejection episodes, potentially suggesting that alloimmune phenomena contributed to the chronic injury. CONCLUSIONS: In conclusion, this study provides better insight in the eventual causes of graft failure, and their relative contribution, highlighting the weight of nonimmune causes. Future efforts aimed to improve outcome after kidney transplantation should align with the relative weight and expected impact of targeting these causes.
Authors: Stan Benjamens; Saleh Z Alghamdi; Elsaline Rijkse; Charlotte A Te Velde-Keyzer; Stefan P Berger; Cyril Moers; Martin H de Borst; Riemer H J A Slart; Frank J M F Dor; Robert C Minnee; Robert A Pol Journal: J Clin Med Date: 2021-01-17 Impact factor: 4.241
Authors: Tambi Jarmi; Samir Khouzam; Nitika Shekhar; Meray Hosni; Launia White; David O Hodge; Martin L Mai; Hani M Wadei Journal: J Clin Med Res Date: 2020-12-18
Authors: Elisabet Van Loon; Baptiste Lamarthée; Henriette de Loor; Amaryllis H Van Craenenbroeck; Sophie Brouard; Richard Danger; Magali Giral; Jasper Callemeyn; Claire Tinel; Álvaro Cortés Calabuig; Priyanka Koshy; Ben Sprangers; Dirk Kuypers; Wilfried Gwinner; Dany Anglicheau; Pierre Marquet; Maarten Naesens Journal: Kidney Int Date: 2022-05-05 Impact factor: 18.998
Authors: Massini A Merzkani; Andrew J Bentall; Byron H Smith; Xiomara Benavides Lopez; Matthew R D'Costa; Walter D Park; Walter K Kremers; Naim Issa; Andrew D Rule; Harini Chakkera; Kunam Reddy; Hasan Khamash; Hani M Wadei; Martin Mai; Mariam P Alexander; Hatem Amer; Aleksandra Kukla; Mireille El Ters; Carrie A Schinstock; Manish J Gandhi; Raymond Heilman; Mark D Stegall Journal: Transplant Direct Date: 2022-01-13