Abstract

Introduction Renal transplant recipients (RTR) are at higher mortality risk compared to controls, and have an increased risk of developing malignancies mainly due to long-term use of immunosuppressive medication. Vitamin C is a well-known radical scavenger and reducing agent that may exhibit protective properties against malignant diseases. We aimed to investigate the association between plasma vitamin C and long-term mortality due to malignancy in a large cohort of RTR. Materials & Methods Observational prospective cohort study. RTR with a functioning allograft ≥1 year were recruited at a single university setting between 2001 and 2003. Plasma vitamin C was measured at baseline using reversed phase liquid chromatography with fluorescence. RTR visited the outpatient clinic with declining frequency, in accordance with the American Transplantation Society Guidelines. There was no loss during follow-up. Death due to malignancy was defined as death due to any type of malignancy (International Classification of Diseases, 10th revision (ICD-10) codes C00-C97). Multivariable Cox-proportional hazards regression analyses were performed to assess the association between vitamin C and mortality risk due to malignancy diseases. Results We included 598 patients (mean age 51±12 years, 55% male, 97% caucasian). Mean plasma vitamin C was 44±20 μmol/L. After a median follow-up of 7.0 [IQR, 6.2-7.5] years, 131 (22%) patients died, of whom 32 (24%) were due to malignancy. In multivariable Cox regression analyses, plasma vitamin C was inversely associated with risk of death due to malignancy (HR 0.42; 95% CI 0.24-0.75, P=0.003), independent of several potential confounders including age, sex, body mass index, estimated Glomerular Filtration Rate, proteinuria, dialysis vintage time since transplantation, and immunosuppressive therapy. Similar results were found through tertiles of vitamin C. Conclusion Malignancy is a substantially prevalent individual cause of death after renal transplantation. Plasma vitamin C levels are inversely and independently associated with risk of mortality due to malignancy. These findings suggest that vitamin C may be an overlooked modifiable risk factor of death due to malignancy in RTR. Whether a novel therapy based on vitamin C supplementation may represent an opportunity to decrease deaths due to malignancy in RTR requires further studies.