Abstract
Recent studies have shown that depletion of vitamin C is frequent in outpatient kidney transplant recipients (KTR) and that vitamin C is inversely associated with risk of death. Whether plasma vitamin C is associated with death-censored kidney graft failure remains unknown. We investigated KTR who participated in the TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study. The primary outcome was graft failure (restart of dialysis or re-transplantation). Overall and stratified (pinteraction < 0.1) multivariable-adjusted Cox regression analyses are presented here. Among 598 KTR (age 51 ± 12 years-old; 55% males), baseline median (IQR) plasma vitamin C was 44.0 (31.0–55.3) µmol/L. Through a median follow-up of 9.5 (IQR, 6.3‒10.2) years, 75 KTR developed graft failure (34, 26, and 15 events over increasing tertiles of vitamin C, log-rank p < 0.001). Plasma vitamin C was inversely associated with risk of graft failure (HR per 1–SD increment, 0.69; 95% CI 0.54–0.89; p = 0.004), particularly among KTR with triglycerides ≥1.9 mmol/L (HR 0.46; 95% CI 0.30–0.70; p < 0.001; pinteraction = 0.01) and among KTR with HDL cholesterol ≥0.91 mmol/L (HR 0.56; 95% CI 0.38–0.84; p = 0.01; pinteraction = 0.04). These findings remained materially unchanged in multivariable-adjusted analyses (donor, recipient, and transplant characteristics, including estimated glomerular filtration rate and proteinuria), were consistent in categorical analyses according to tertiles of plasma vitamin C, and robust after exclusion of outliers. Plasma vitamin C in outpatient KTR is inversely associated with risk of late graft failure. Whether plasma vitamin C‒targeted therapeutic strategies represent novel opportunities to ease important burden of graft failure necessitates further studies.
Highlights
Kidney transplantation is the optimal therapy for patients with end-stage kidney disease, in terms of survival, life quality, and cost effectiveness [1,2]
Our results consistently show that outpatient kidney transplant recipients (KTR) in the highest tertile of plasma vitamin C are at significantly lower risk of long-term kidney graft failure, independently of donor, recipient, and transplant characteristics, including Estimated glomerular filtration rate (eGFR) and proteinuria
These results suggest that plasma vitamin C is an independent risk factor for long-term graft failure in outpatient KTR, pointing towards the need for further evaluating potential underlying mechanisms linking plasma vitamin C with lower risk of graft failure, while suggesting the involvement of mechanisms pertaining to the effect of circulating lipids on risk of graft failure, high-density lipoprotein (HDL) cholesterol and triglycerides
Summary
Kidney transplantation is the optimal therapy for patients with end-stage kidney disease, in terms of survival, life quality, and cost effectiveness [1,2]. Despite this success, the frequent occurrence of graft failure necessitating return to dialysis or re-transplantation remains an important medical problem that represents a constant threat for kidney transplant recipients (KTR) [3,4]. The frequent occurrence of graft failure necessitating return to dialysis or re-transplantation remains an important medical problem that represents a constant threat for kidney transplant recipients (KTR) [3,4] This is underscored by studies reporting that KTR regard return. Taking into account, the scarcity of donor organs, prevention of re-transplantation by improving graft survival stands as an issue of paramount importance as it may translate into relief of existing organ shortage [11], underscoring a great need for identifying potentially modifiable risk factors to decrease the burden of late graft failure
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