Remnant Cholesterol is Prospectively Associated With Cardiovascular Disease Events and All-Cause Mortality in Kidney Transplant Recipients


Reuben William Horace; Mary Roberts; Theresa I. Shireman; Basma Merhi; Paul Jacques; Andrew G. Bostom; Simin Liu; Charles B. Eaton


Nephrol Dial Transplant. 2022;37(2):382-389. 

In This Article

Abstract and Introduction


Graphical Abstract

Background: The cholesterol content of circulating triglyceride-rich lipoproteins is characterized as remnant cholesterol, although little is known about its role in the development of cardiovascular disease (CVD) outcomes, all-cause mortality or transplant failure in kidney transplant recipients (KTRs). Our primary aim was to investigate the prospective association of remnant cholesterol and the risk of CVD events in renal transplant recipients with secondary aims evaluating remnant cholesterol and renal graft failure and all-cause mortality among participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial.

Methods: Among 4110 enrolled participants, 98 were excluded for missing baseline remnant cholesterol levels and covariates. Nonfasting remnant cholesterol levels were calculated based on the lipid profiles in 3812 FAVORIT trial participants at randomization. A Wilcoxon-type test for trend was used to compare baseline characteristics across remnant cholesterol quartiles. Cox proportional hazards regression was used to evaluate the association of baseline remnant cholesterol levels with time to primary and secondary study outcomes.

Results: During a median follow-up of 4.0 years we documented 548 CVD incident events, 343 transplant failures and 452 all-cause deaths. When comparing the highest quartile (quartile 4) to quartile 1, proportional hazard modeling revealed a significant increase in CVD risk {hazard ratio [HR] 1.32 [95% confidence interval (CI) 1.04–1.67]} and all-cause mortality risk [HR 1.34 (95% CI 1.01–1.69)]. A nonsignificant increase in transplant failure was seen as well [HR 1.20 (95% CI 0.87–1.64)].

Conclusions: Remnant cholesterol is associated with CVD and all-cause mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of remnant cholesterol-lowering therapy on these outcomes may be warranted.

Additional Content: An author video to accompany this article is available at:


Remnant cholesterol is the cholesterol content of triglyceride-rich lipoproteins and is composed of very-low-density lipoproteins (VLDLs)[1] and intermediate-density lipoproteins (IDLs) in the fasting state and of VLDL, IDL and chylomicron remnants in the nonfasting state. Patients with chronic kidney disease (CKD), particularly those with renal transplantation, are at increased risk of developing cardiovascular disease (CVD).[2] CVD in turn also enhances the rapidity of progression of CKD as is seen in the Chronic Renal Insufficiency Cohort study.[3] Along with CKD progression, metabolic abnormalities may progress further, contributing to atherosclerotic changes and adversely affecting renal function.[2,4] Rates of CVD death in kidney transplant recipients (KTRs) remain higher than in the general population, with the rate of CVD death 10 times higher and the annual rate of fatal or nonfatal cardiovascular events 50 times that of the general population.[4]

Remnant cholesterol in both fasting and nonfasting states is associated with inflammation, oxidative stress, accelerated atherosclerosis and ischemic heart disease.[1–10] Higher levels of triglycerides or non-high-density lipoprotein (HDL) cholesterol in chronic KTRs have been associated with CVD (mainly coronary heart disease) outcomes, total mortality and renal graft loss.[1] While remnant cholesterol, elevated triglycerides and non-HDL cholesterol are correlated, remnant cholesterol remains a distinct class of lipoproteins and therefore its role in cardiovascular outcomes and all-cause mortality in KTRs is unknown.

Therefore our primary aim was to evaluate the association of remnant cholesterol in renal transplant recipients (RTRs) and the risk of CVD events, with secondary aims of evaluating the association of remnant cholesterol and renal graft failure, all-cause mortality and CVD events, using the large Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial cohort.