Role of standard HLA mismatch in modifying associations between non-pharmacologic risk factors and solid organ malignancy after kidney transplantation |
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| Affiliation: | 1. Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA;2. Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United States of America;3. Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, RI, USA;1. Departamento de Nefrologia, Centro Hospitalar do Médio Tejo, Torres Novas, Portugal;2. Departamento de Nefrologia, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;3. Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal;4. Serviço de Urologia e Transplantação Renal, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;1. Faculty of Medical Sciences, Belo Horizonte, Minas Gerais, Brazil;2. University Hospital of the Faculty of Medical Sciences, Belo Horizonte, Minas Gerais, Brazil;3. IMUNOLAB – Laboratory of Histocompatibility, Belo Horizonte, Minas Gerais, Brazil;4. Institute of Research and Education of the Hospital Santa Casa, Belo Horizonte, Minas Gerais, Brazil;1. Department of Nephrology, Gaziantep University School of Medicine, Gaziantep, Turkey;2. Şanlıurfa Training and Research Hospital, Şanlıurfa, Turkey;1. Department of Cardiovascular Surgery, 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China;2. Department of Ophthalmology, 4th Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, China;1. Hematology Darpartment, The Seventh Affiliated Hospital of Sun Yat-sen University, China;2. Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, China |
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| Abstract: | BackgroundHuman leukocyte antigen mismatch(es) (HLA-mm) between donors and recipients has not been extensively studied either as a risk factor for solid organ malignancy (SOM) or as a modifier of associations between nonpharmacologic risk factors and SOM in kidney transplant recipients (KTRs).MethodsIn a secondary analysis from a previous study, 166,256 adult KTRs in 2000–2018 who survived the first 12 months post-transplant free of graft loss or malignancy were classified into 0, 1–3, and 4–6 standard HLA-mm cohorts. Multivariable cause-specific Cox regressions analyzed the risks of SOM and all-cause mortality (ac-mortality) in 5 years following the first KT year. Comparisons of associations between SOM and risk factors in HLA mismatch cohorts were made by estimating the ratios of adjusted hazard ratios.ResultsCompared with 0 HLA-mm, 1–3 HLA-mm was not associated, and 4–6 HLA-mm was equivocally associated with increased risk of SOM [hazard ratio, (HR) = 1.05, 95%, confidence interval (CI) = 0.94–1.17 and HR = 1.11, 95% CI = 1.00–1.34, respectively]. Both 1–3 HLA-mm and 4–6 HLA-mm were associated with increased risk of ac-mortality compared with 0 HLA mm [hazard ratio (HR) = 1.12, 95%, Confidence Interval (CI) = 1.08–1.18) and (HR = 1.16, 95% CI = 1.09–1.22), respectively]. KTR's history of pre-transplant cancer, age 50–64, and >/=65 years were associated with increased risks of SOM and ac-mortality in all HLA mismatch cohorts. Pre-transplant dialysis >2 years, diabetes as the primary renal disease, and expanded or standard criteria deceased donor transplantation were risk factors for SOM in the 0 and 1–3 HLA-mm cohorts and of ac-mortality in all HLA-mm cohorts. KTRs male sex or history of previous kidney transplant was a risk factor for SOM in the 1–3 and 4–6 HLA-mm cohorts and of ac-mortality in all HLA-mm cohorts.ConclusionDirect association between SOM and the degree of HLA mismatching is equivocal and limited to the 4–6 HLA-mm stratum; however, the degree of HLA mismatching has significant modifying effects on the associations between specific nonpharmacologic risk factors and SOM in KTRs. |
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