title: Radiation dose associated with renal failure mortality: a potential pathway to partially explain increased cardiovascular disease mortality observed after whole-body irradiation.
abstract: Whole-body and thoracic ionizing radiation exposure are associated with increased cardiovascular disease (CVD) risk. In atomic bomb survivors, radiation dose is also associated with increased hypertension incidence, suggesting that radiation dose may be associated with chronic renal failure (CRF), thus explaining part of the mechanism for increased CVD. Multivariate Poisson regression was used to evaluate the association of radiation dose with various definitions of chronic kidney disease (CKD) mortality in the Life Span Study (LSS) of atomic bomb survivors. A secondary analysis was performed using a subsample for whom self-reported information on hypertension and diabetes, the two biggest risk factors for CRF, had been collected. We found a significant association between radiation dose and only our broadest definition of CRF among the full cohort. A quadratic dose excess relative risk model [ERR/Gy(2) = 0.091 (95% CI: 0.05, 0.198)] fit minimally better than a linear model. Within the subsample, association was also observed only with the broadest CRF definition [ERR/Gy(2) = 0.15 (95% CI: 0.02, 0.32)]. Adjustment for hypertension and diabetes improved model fit but did not substantially change the ERR/Gy(2) estimate, which was 0.17 (95% CI: 0.04, 0.35). We found a significant quadratic dose relationship between radiation dose and possible chronic renal disease mortality that is similar in shape to that observed between radiation and incidence of hypertension in this population. Our results suggest that renal dysfunction could be part of the mechanism causing increased CVD risk after whole-body irradiation, a hypothesis that deserves further study.
authors.affiliation: Department of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY14642-0644, USA. Jacob_Adams@URMC.Rochester.edu
authors.forename: Michael Jacob
authors.initials: MJ
authors.lastname: Adams
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Grant
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kodama
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Kasagi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Suyama
authors.forename: Ritsu
authors.initials: R
authors.lastname: Sakata
authors.forename: Masazumi
authors.initials: M
authors.lastname: Akahoshi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001822:Body Burden; D002318:Cardiovascular Diseases / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009689:Nuclear Warfare; D015995:Prevalence; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000401:mortality*; D051437:Renal Insufficiency / Q000401:mortality*; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate; D017741:Survivors; D014916:Whole-Body Irradiation / Q000706:statistics & numerical data*; D055815:Young Adult