High serum PCSK9 is associated with increased risk of new-onset diabetes after transplantation in renal transplant recipients

Abstract

OBJECTIVE New-onset diabetes after transplantation (NODAT) is a major complication in renal transplant recipients (RTRs). Cholesterol metabolism has been linked to diabetes development. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is crucial in LDL receptor regulation. Its association with NODAT is unknown. We prospectively determined the association between serum PCSK9 levels and NODAT development and then with all-cause mortality, cardiovascular mortality, and renal graft failure. RESEARCH DESIGN AND METHODS In a university setting, nondiabetic RTRs recruited between 2001 and 2003 with a functional graft for ≥1 year were eligible. Serum PCSK9 was measured by ELISA. Cox proportional hazards analysis was used to assess the association of PCSK9 with the development of NODAT, all-cause mortality, cardiovascular mortality, and graft failure. RESULTS In 453 RTRs (age 51 ± 12 years, 56% male; 6.1 [2.7–11.7] years after transplantation), serum PCSK9 was 107.1 ± 43.4 μg/L. During a median follow-up of 10 years, 70 RTRs developed NODAT, 123 died, and 59 developed graft failure. NODAT occurred more frequently in the upper PCSK9 tertile (23%) versus the lowest two PCSK9 tertiles (12%; P CONCLUSIONS Circulating PCSK9 is associated with NODAT in RTRs. The PCSK9 pathway may contribute to the pathogenesis of NODAT.