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. SerumPCSK9 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 51612 years, 56%male; 6.1 [2.7-11.7] years after transplantation), serumPCSK9 was 107.1643.4mg/L. During amedian 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 < 0.001). In crude Cox regression analyses, PCSK9was significantly associated with development of NODAT (hazard ratio 1.34 [95% CI 1.10-1.63]) per SD change (P = 0.004). This association remained independent of adjustment for potential confounders, including statin use. PCSK9was not associatedwith all-causemortality, cardiovascular mortality, or graft failure. Conclusions: Circulating PCSK9 is associated with NODAT in RTRs. The PCSK9 pathway may contribute to the pathogenesis of NODAT.