Apolipoprotein B-48 and late graft failure in kidney transplant recipients

Introduction Transplant vasculopathy resembles atherosclerotic plaque formation and is a major contributor to late graft failure in kidney transplant recipients (KTR). Remnant lipoproteins and associated triglycerides are causal risk factors for atherosclerotic plaques and have been implicated in late kidney graft failure. However, whether remnants derived from liver (containing apolipoprotein [apo] B100) or intestine (containing apoB48) are clinically more important is unclear. The current study investigated the association between baseline fasting apoB48 levels and late kidney graft failure. Methods 481 KTR with a functioning graft for at least 1 year were included in this retrospective, observational longitudinal single center cohort study. The primary endpoint was death-censored late graft failure, defined as need for initiation of dialysis or re-transplantation. ApoB48 was measured by enzyme-linked immunosorbent assay. Results During a median follow-up of 9.5 years, 61 KTR developed graft failure (12.7%). At baseline, KTR with higher apoB48 levels had lower eGFR (P < .001), lower high-density lipoprotein (HDL) cholesterol (P < .001), increased triglycerides (P < .001) and used cyclosporine more frequently (P = .003). Cox regression showed that higher baseline apoB48 was associated with higher risk of late graft failure [hazard ratio (95% confidence interval), 1.59 (1.22, 2.07), P < .001], independent of stepwise adjustment for potential confounders, including age and sex, immunosuppression type and proteinuria, triglycerides, and waist circumference (fully adjusted HR, 1.78 (1.29, 2.47), P < .001]. Conclusion ApoB48 is strongly associated with late graft failure, independent of potential confounders. Since apoB48-containing lipoproteins originate from the intestine, this study provides a rationale for considering pharmacological interventions targeting lipid absorption to improve graft outcome.